2021 Fall Prime Therapeutics Report

Atopic Dermatitis: Therapeutic Advances and Payer Impact

Lupus and Lupus

Nephritis: Advances in Treatment and Management

Alzheimer’s Disease: Treatment Update

Chronic Kidney Disease: Emerging Therapies and Management Strategies

Dry Eye Disease: Changing Treatment and Management Landscape

Published By

Magellan Rx Management

4801 E. Washington St., Ste. 100 Phoenix, AZ 85034

Tel: 401-344-1000

Fax: 401-619-5215

magellanrx.com

Editor

Lindsay Speicher, J.D.

Project Manager, Magellan Method lspeicher@magellanhealth.com 401-344-1105

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Carole Kallas ckallas@magellanhealth.com 401-344-1132

The content of Magellan RxTM Report — including text, graphics, images, and information obtained from third parties, licensors, and other material (“content”) — is for informational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Magellan RxTM Report does not verify any claims or other information appearing in any of the advertisements contained in the publication and cannot take responsibility for any losses or other damages incurred by readers in reliance on such content. Developed by D Custom.

Contributors

Caroline Carney, M.D., M.Sc., FAPM, CPHQ CMO, Magellan Health, Magellan Rx Management

Steve Cutts, Pharm.D. SVP, Market General Manager, MRx Specialty

Haita Makanji, Pharm.D. VP, Clinical Strategy and Innovation, Specialty

Misty Grefcz Director, Marketing

Joe Tavares SVP, Sales and Business Development, Specialty

Corrado Panno VP, Business Development, Magellan Method

Stacy Inman, Pharm.D.

Senior Clinical Project Manager, Magellan Method

Carole Kallas

Project Manager

Brian Kinsella, Esq.

Senior Legal Counsel

Editorial Advisory Board

Mona M. Chitre, Pharm.D., CGP

Chief Pharmacy Ofcer & VP Clinical Analytics, Strategy & Innovation, Excellus BlueCross BlueShield

Dennis Bourdette, M.D., FAAN, FANA

Chair and Roy and Eulalia Swank Family Research Professor, Department of Neurology, Oregon Health & Science University

Yousaf Ali, M.D., FACR

Chief, Division of Rheumatology, Mount Sinai West; Professor of Medicine, Icahn School of Medicine at Mount Sinai

Steven L. D’Amato, B.S.Pharm. Executive Director, New England Cancer Specialists

Joseph Mikhael, M.D., M.Ed., FRCPC, FACP

Saira A. Jan, M.S., Pharm.D. Director of Pharmacy Strategy and Clinical Integration, Horizon BlueCross BlueShield of New Jersey IN THIS ISSUE | Fall 2021

Alina Young Associate Legal Counsel

Lilly Ackley VP, Corporate Communications

Maria James Director, External Communications

Chief Medical Ofcer, International Myeloma Foundation

Natalie Tate, Pharm.D., MBA, BCPS VP, Pharmacy Management, BlueCross BlueShield of Tennessee

Steve Marciniak, R.Ph. Director II, Medical Beneft Drug Management, BlueCross BlueShield of Michigan

A NOTE FROM OUR CMO

Dear Managed Care Colleagues,

Welcome to our fall 2021 issue of the Magellan Rx Report! This year has been exciting, ith the frst FDA approval of a COVID vaccine and more than million Americans having received at least one dose as of press time Other healthcare spaces have seen innovation and advancement as ell, ith novel therapy approvals and more anticipated efore the end of the year Magellan Management is committed to providing our readers ith trending clinical advances, approvals, and updates

Our cover story page focuses on Alzheimer s disease and the long a aited approval in this category, along ith an e panded pipeline and the impact ne treatment options may have for payers

In another article, e highlight the management of lupus and lupus nephritis page o ne approvals indicated for lupus nephritis ill open more treatment options and re uire payers to strategize and manage the category e ectively

e outline the e panding treatment landscape for atopic dermatitis in another article page , specifcally the iologics in the pipeline anticipated over the ne t fe years and ho added treatment options may change management approaches

Other timely topics in this issue include updates on dry eye disease page and chronic idney disease page , a iosimilar pipeline page , and a spotlight on Magellan s nhanced Utilization Management Program for High Cost herapies page As al ays, the issue is rounded out ith our pipeline update page and managed care ne sstand page

o learn more a out Magellan Management and our support for payer initiatives of the future, please feel free to contact us at Magellan eport magellanhealth com As al ays, e value any feed ac you may have I hope you en oy the report

Sincerely,

Caroline Carney, M.D., M.Sc., FAPM, CPHQ Chief Medical Ofcer Magellan Health & Magellan Rx Management

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MANAGED CARE

NEWSSTAND

Senate Finance Leaders Seek Ideas to Address Barriers to Mental Health Care

Senate Finance Chairman Ron Wyden (D-OR) and ranking member Mike Crapo (R-ID) released a letter to Senate colleagues Sept. 21 seeking input from stakeholders across the healthcare continuum to help inform how Congress can address barriers to mental health care. While requesting ideas in all areas, the leaders asked for input around workforce shortages, access and care coordination issues, telehealth, and increasing access to behavioral healthcare for children and young people. The committee hopes to work on a bipartisan mental health bill over the remainder of the year.

New Federal Vaccine Requirements

On Sept. 9, President Biden announced new federal vaccination requirements in the context of a new action plan: Path Out of the Pandemic. The vaccine rules will apply to federal workers, large employers, and healthcare sta hese ne regulations are in response to the increased surge in COVID-19 cases across the nation.

Senators Release White Paper Reimagining Mental Health

On Sept. 9, Sens. Michael Bennet (D-CO) and John Cornyn (R-TX) released a white paper, “A Bold Vision for America’s Mental Well-being,” which presents a framework for modernizing, reimagining, and redesigning the mental health and substance use disorder systems of care.

The white paper outlines key steps that Congress can take to improve both. The senators are seeking feedback and input “from experts, community leaders, and constituents on policies to help achieve intended outcomes laid out in their white paper.” They intend to use the feedback to “inform a forthcoming legislative package.”

HHS Secretary Xavier Becerra Releases Plan to Address Prescription Drug Costs

The U.S. Department of Health and Human Services (HHS) released its Comprehensive Plan for Addressing High Drug Prices Sept. 9. The report responds to the request included in President Biden’s “Executive Order on Promoting Competition in the American Economy” for “a plan to continue the e ort to com at e cessive pricing of prescription drugs and enhance domestic pharmaceutical supply chains, to reduce the prices paid by the federal government for such drugs, and to address the recurrent problem of price gouging.” Overall, the report does not include any new policies. While the list of proposals is long, most include few details beyond discussion of the basic concepts that would need to e eshed out via rule ma ing or collaboration with Congress.

The report presents principles for equitable drug-pricing reform through competition, describes various congressional initiatives that are underway, and summarizes administrative actions and HHS proposals. The report outlines three guiding principles for HHS’ regulatory actions and legislative proposals relating to drug pricing. Each guiding principle includes specifc legislative and regulatory recommendations. These align closely with the Biden administration’s Aug. 12 congressional priorities for prescription drug-pricing legislation.

While requesting ideas in all areas, the leaders asked for input around workforce shortages, access and care coordination issues, telehealth, and increasing access to behavioral healthcare for children and young people.

House Begins Markup of Build Back Better Act

During the week of Sept. 7, committees of jurisdiction in the House of Representatives began to mark up portions of the Build Back Better Act, a plan that includes various pieces of President Biden’s American Jobs Plan and American Families Plan. The $3.5 trillion budget reconciliation pac age includes signifcant ne investments in healthcare, child care, paid family and medical leave, higher education, workforce training, and more. It is being developed and considered pursuant to a

fscal year udget resolution adopted in late August. This allows the Senate to pass the legislation by a simple majority and ithout eing su ect to a fli uster Several House committees began marking up the draft legislation last week. The House intended to complete the process this week, aiming to have the full reconciliation pac age on the House oor for a vote by the end of the month.

The Ways and Means Committee and the Energy and Commerce Committee proposals would phase in vision, hearing, and dental enefts in , , and , respectively. The legislation would also make broad changes to prescription drug coverage under Medicare. In an attempt to address high prescription drug prices, the proposal includes the Elijah E. Cummings Lower Drug Costs Now Act (H.R. 3). It would require HHS to negotiate prices with drug manufacturers, require drug manufacturers that increase prices faster than in ation to pay back that excess amount to the government, and cap out-of-pocket costs for Medicare Part D enefciaries at $2,000 per year. In addition, the legislation includes a repeal of the rebate rule. These proposals are a starting point in what is expected to be a rigorous budget reconciliation process. With narrow majorities in both chambers, Democrats are working to fnalize the pac age uic ly in hopes of moving it concurrently with the bipartisan infrastructure bill. Once the committees of jurisdiction have approved their legislation, the House Budget Committee and House Rules Committee will consider the bill before it is voted on by the full House. After the reconciliation package advances in the House, the Senate will begin its consideration.

CMS Releases Bulletin on Third Party Liability in Medicaid

On Aug. 27, the U.S. Centers for Medicare & Medicaid Services (CMS) released a

Center Informational Bulletin to assist states in ensuring that their Medicaid state plans comply with Third Party Liability (TPL) re uirements re ected in current la s CMS notes that states should update their Medicaid TPL state plan pages and submit amendments to CMS to re ect the recent changes in law. As states make changes in their TPL programs, they will likely lead to implications for Medicaid-managed care plan contracts.

Congress Passes $3.5 Trillion Budget Resolution, Begins Developing Legislative Details

The House of Representatives returned in the middle of August and passed a $3.5 trillion budget resolution Aug. 24, after days of internal negotiations within the House Democratic Caucus. The 220-212 vote came with only Democratic members in support. The budget resolution follows similar action by the U.S. Senate, which passed the bill on a 5049 partisan vote earlier in August. Key to the agreement in the House was that the budget resolution would move in tandem with the bipartisan infrastructure bill. Lawmakers must now work on developing the legislative details surrounding the broad instructions contained in the budget resolution, which calls for extended subsidies of the A orda le Care Act ACA and the childcare tax credit that was passed earlier this year; universal pre-K and free community college; funding to combat climate change; committees to develop legislation to provide dental, vision, and hearing enefts in Medicare, reform the part D program, and limit out-of-pocket costs for Medicare enefciaries and Medicare negotiation of high-cost drugs facing little or no competition. In order for this legislation to pass, it will require that nearly all Democratic mem ers support a fnal ill, since no Republicans are likely to support this package.

FDA Grants Full Approval of Pfzer-BioNTech Vaccine

On Aug. 23, the U.S. Food and Drug Administration (FDA) granted full approval for the use of the Pfzer BioN ech COVID vaccine, now marketed as Comirnaty, for the prevention of COVID-19 in individuals 16 and older. The vaccine continues to be available under emergency use authorization (EUA), including for individuals ages 12 through 15 and for a third dose in certain immunocompromised individuals. Data has also been submitted for vaccine use in individuals ages 5 through he FDA is re uiring Pfzer to conduct post-marketing studies to further assess the risks of myocarditis and pericarditis following vaccination. In addition, although not re uired y the FDA, Pfzer has committed to additional post-marketing safety studies, including a pregnancy registry study to evaluate pregnancy and infant outcomes after vaccination during pregnancy.

Medicare will reimburse providers for the booster shot at the same rate that they reimburse for any other coronavirus vaccine dose.

CMS announced Aug. 13 that immunocompromised individuals will receive the coronavirus booster shot without cost-sharing.

FDA Updates EUAs for COVID-19 Vaccines

CMS announced Aug. 13 that immunocompromised individuals will receive the coronavirus booster shot without cost-sharing. This follows the FDA announcement updating the UA for oth the Pfzer BioN ech and Moderna COVID-19 vaccines, allowing immunocompromised people to receive a third dose of the vaccine at least days following the two-dose regimen to further boost protection. CMS announced that Medicare would cover the administration costs for the coronavirus vaccine booster shots. Medicare will reimburse providers for the booster shot at the same rate that they reimburse

for any other coronavirus vaccine dose. The national average payment rate for immunization administrators is $40 per coronavirus vaccine dose. The agency promised to share more information about billing and coding for booster shots in the near future.

President Biden Calls on Congress to Reduce Drug Costs by Allowing Medicare to Negotiate Price of Drugs

President Biden spoke from the White House on Aug. 12 to urge Congress to include several provisions in the $3.5 trillion reconciliation bill that passed the U.S. Senate the day before. The president urged Congress to include detailed legislative authority for Medicare to negotiate directly with manufacturers on expensive drugs that face little or no competition. He also called on Congress to limit future price increases to no more than the in ation rate, ith any increases above that being returned as a rebate. At the event, he also called for limits to Medicare enefciary out of-pocket costs and urged that legislation be passed to allow for drug importation from Canada. The reconciliation bill passed by the Senate provides broad spending outlines. The bill must now be passed by the House of Representatives. Following passage in both chambers, the committees of jurisdiction must write detailed tax and spending plans within these guidelines. It is likely that this work, if the House passes the budget bill, will occupy lawmakers through the end of the year. The reconciliation process has no Republican support in either chamber at this point. For legislation to pass, it will require all 50 Democratic senators to support any fnal pac age that details tax and spending policies. In the House, the speaker can lose only three Democratic votes if these spending bills are to become law. Government negotiation of drugs is one of many contentious budget issues in the

reconciliation package as Congress begins work on the 2022 legislative budget process.

Chamber of Commerce and PCMA File Lawsuits Challenging Transparency in Coverage Rule

The U.S. Chamber of Commerce and the Pharmaceutical Care Management Association PCMA fled separate la suits Aug 10 and 12 to challenge the Trump administration’s Transparency in Coverage rule. On Nov. 12, 2020, the departments of HHS, reasury, and a or issued a fnal rule titled ransparency in Coverage he fnal rule requires issuers to disclose historical net prices for drugs at the National Drug Code level for each applicable plan, beginning in , on machine reada le fles In addition, the rule requires issuers to create an enrollee self-service online tool that would return estimated cost-sharing for covered items and services beginning in 2023 for a select set of services and in 2024 for drugs and all other items and services.

Senate Passes Infrastructure Bill and Budget Reconciliation Package

The U.S. Senate passed a $1.2 trillion bipartisan infrastructure bill 69-30 Aug. 10 after weeks of negotiation between Democratic and Republican senators and the White House. The package includes funding for roads, bridges, mass transit, and broadband. It is the largest investment in U.S. infrastructure in decades. To help pay for the bill, the Trump-era rebate rule will be delayed by three years, until 2026, providing savings of approximately $50 billion. The following day, the Senate also passed on a 50-49 partisan vote a $3.5 trillion budget reconciliation package that Democrats have called its investment in families, or American Families Plan.

CMS Revokes Medicaid Work Requirement in Three States

On Aug. 10, CMS sent letters to health offcials in Ohio, South Carolina, and Utah informing the states that the Biden administration was reversing Trump-era approvals of work requirements for their Medicaid populations In , the rump administration issued guidance to let states implement or rules for the frst time, arguing that the move would help healthy people fnd employment No state had Medicaid or re uirements in e ect at the eginning of the Biden administration, as the requirements had been halted amid court challenges and the COVID-19 pandemic.

Agencies Release 2021 ACA, CAA Implementation FAQs

The departments of Labor, HHS, and Treasury released an 11-page set of frequently asked questions (FAQs) Aug. 10 regarding the implementation of the 2021 ACA and the 2021 Consolidated Appropriations Act (CAA), including provisions of Title I (The No Surprises Act) and Title II (Transparency) of Division BB of the CAA. The guidance also addresses components of the Transparency in Coverage Final Rules, as well as the a gencies’ approach to enforcing the following provisions:

• Machine reada le fles

• Price comparison tools.

• Health plan/issuer ID cards.

• Good faith estimates.

• Advanced e planation of enefts (EoBs).

• Gag clauses.

• Directories.

• Balance billing disclosures.

• Continuity of care.

• Treatment of grandfathered health plans.

• eporting on pharmacy enefts and drug costs.

Notably, the agencies will defer until July , , enforcement of the fnal rules that require health plans and issuers to publish machine reada le fles related to prescription drugs while it considers, through notice-and-comment rulemaking, whether the requirement remains appropriate. The agencies intend to propose rulemaking with respect to price comparison tools, ID cards, good faith estimates, advanced EoBs, directories, balance billing, continuity of care, and pharmacy enefts and, in most cases, are asking for good faith compliance pending rulemaking. Where states are primary enforcers of the applicable provisions, HHS encourages them to take a similar enforcement approach. The agencies make clear that they will not determine that a state is failing to substantially enforce this requirement if it takes this approach.

CMS Proposes to Rescind Medicare Part B Drug Most Favored Nation Model

On Aug. 6, CMS released a proposed rule that would rescind the controversial Most Favored Nation (MFN) Model. The MFN Model was announced in November 2020, in the fnal months of the rump administration, through an interim fnal rule ith comment (IFC). The model would have tied payment for certain drugs administered under Medicare Part B to international prices. The MFN Model was mandatory and scheduled to run for seven years, beginning in January 2021. Approximately 50 high-spend drugs would have been included. However, shortly after the announcement of the model and release of the IFC, four lawsuits were fled that challenged the legality of the demonstration and the use of an interim fnal rule instead of the traditional rulemaing pathway. As a result, preliminary injunctions were issued, and the MFN Model did not begin on Jan. 1. The injunction, procedural issues noted by multiple courts, and stakeholder concerns prompted CMS to rescind the Novem er interim fnal rule The agency says that rescinding the rule

addresses the procedural defciencies and allows for time to further consider public comments. CMS indicates that “this action does not re ect any udgement y HHS regarding future policy.” The proposed rule states that HHS is exploring opportunities to promote value-based care and address high Medicare Part B drug costs, manufacturer pricing, and the associated growth in Medicare spending.

The proposed rule states that the U.S. Department of Health and Human Services is exploring opportunities to promote valuebased care and address high Medicare Part B drug costs, manufacturer pricing, and the associated growth in Medicare spending.

Atopic Dermatitis:

Therapeutic Advances and Payer Impact

As the AD pipeline pic s up speed, payers ill consider ho to e ectively manage the in u of options and correct for discrepancies in access to care

Kathryn Lindhorst Canaday, Pharm.D. VP, Pharmacy Medical Mutual

Atopic dermatitis AD , sometimes called eczema, is the most common chronic in ammatory s in disease and a ects around of the U S population Most individuals living ith AD are children or adolescents 1 Onset of AD typically occurs y age around of patients develop AD in the frst year of life and ithin the frst fve years , hile AD often resolves y the time patients reach adulthood, up to of patients ill e perience continued symptoms 2, 4

he primary symptom of AD is an itchy rash It can develop on any s in area, ut it may e more li ely to appear in certain places depending on the patient s age AD can appear as a dry, scaly rash on the chee s in infants, or as a umpy rash that can thic en and turn leathery ith fre uent scratching on nec s, rists, an les, and in the creases et een uttoc s and legs, nees, and el o s in children Adults ith AD may e perience fe er rashes ut have e tremely dry s in that is easily irritated, hand eczema, or eye pro lems such as eczema on the eyelids or cataracts

Burden of AD

Economic Impact

AD has profound economic and social impact as ell as impact on patient and caregiver uality of life Costs attri uted to AD in the U S ere estimated at illion in , Direct medical costs associated with AD can include prescriptions, physician visits, emergency and hospital costs to patients and payers, and over the counter pharmacy costs for patients AD can lead to indirect costs from decreased productivity at or , a senteeism, and detriment to uality of life

Insights from our Medical Pharmacy Experts

Patient Burden

he urden on the patient hen living ith AD can e su stantial children with AD report itching and scratching, sleep challenges, pain, leeding, dietary limitations, and emotional and ehavioral impact such as irrita ility and crying , There are also reported physical and social functioning issues associated ith AD in children, including clothing and athing restrictions, concerns around outdoor play and swimming, and the stigma around AD that can cause strained social relationships ith other children or adults , hile adults ith AD report fe er challenges ith social functioning, uality of life in these patients is a ected y symptoms and emotional impact , Adults with AD reported itching and sleep distur ance as having the most signifcant impact on uality of life ho ever, the involvement of visi le areas of the ody such as the face, as ell as genital involvement, also impaired uality of life ,

Current Treatment

AD is often treated ith topical therapies to control itching and repair the s in he topicals typically used to treat AD are corticosteroids or calcineurin inhi itors, hich are mostly availa le generically 12 Besides these, the most recently approved topical treatment is crisa orole UC ISA®), a topical phosphodiesterase-4

enzyme inhi itor that as, at the time of approval, the frst ne AD treatment in years

Before , there as only one approved iologic for AD, dupiluma DUPI N ® Dupiluma is an in ecta le iologic, or monoclonal anti ody, that inhi its signaling of interleu in and interleu in , hich play a role in the in ammation associated ith AD the treatment is indicated for patients ith moderate to severe AD ho are age or older he American Academy of Dermatology and American Academy of Allergy, Asthma, & Immunology guidelines have not een updated since and , respectively, and thus do not include the ne est therapeutic options for AD, crisa orole and dupiluma

ight therapy treatment is sometimes used for patients ho do not achieve results from topical treatments 12 In some cases, topical or oral anti iotics may e used if the s in rash develops a acterial infection, hich can e common ith infants and young children 12 For some patients ith AD, especially infants and children, food avoidance may e employed in order to prevent the rash from occurring Avoidance of s in irritants and e treme temperatures is also a treatment option in some cases

ATOPIC DERMATITIS

Drug Manufacturer

Status

upadacitini INVO A Vie oral A inhi itor pending ru olitini phosphate a af cream Incyte topical A inhi itor pending a rocitini PF Pfzer oral A inhi itor pending aricitini Olumiant li illy and Company Incyte oral A inhi itor pending (phase three) le ri izuma Genentech li illy and Company S I antagonist phase three pimecrolimus (IDP-124)

Bausch Health Ortho Dermatologics topical macrolide immunosuppressant phase three

ro umilast A Arcutis Biotherapeutics topical PD inhi itor phase three delgocitini O Pharma apan o acco topical A inhi itor phase three tradipitant V Vanda Pharmaceuticals oral N receptor antagonist phase three erme ima Biotech IV S IL-1 antagonist phase two gusacitini ASN

Asana BioSciences oral A inhi itor Sy inhi itor phase two SH eistone Biopharma iangsu Hengrui Medicine oral A inhi itor phase two tapinarof Dermavant Sciences topical NSAID phase two fevipiprant A Novartis oral DP2 (CRTh2) antagonist phase two apremilast (Otezla®)

Celgene Amgen oral PD inhi itor phase two asimadoline

Tioga Pharmaceuticals oral opioid agonist phase two yma in ecta le O ligand inhi itor phase two A A uino Pharmaceuticals oral immunomodulators phase two etrasimod Arena Pharmaceuticals oral S P receptor modulators phase two H yo a irin Amgen IV S O ligand inhi itor phase two

Pipeline

he pipeline for AD is e pansive and imminent, ith multiple ne therapies scheduled for approval in Additional therapies are in phase three and may e approved in See a le a ove for an e panded pipeline

Managed Care Impact

he ma ority of patients ith AD are children, and an estimated of children in the U S are Medicaid insured A signifcant disparity in AD diagnosis and management has een o served hen comparing Medicaid-insured children with children who are commercially insured A 2020 study showed that Medicaid-insured children receive less specialist care, see emergency departments

and urgent care centers more often, and have higher rates of asthma and non atopic comor idities compared ith commercially insured children High potency topical corticosteroids and calcineurin inhi itors are prescri ed less often and prescriptions for antihistamines are more than three times higher in the Medicaid population his assessment suggests a arrier to access to compara le specialty care for Medicaid insured children, specifcally in the management of AD here is a potential for these disparities to increase as more costly therapies enter the mar et

he AD space has moved on from its period of slo therapy approvals ith several iologics and other costly therapies li ely to launch in the coming fe years, payers ill divert attention to effectively managing the in u of options in the category here has

Table 1. Atopic Dermatitis Pipeline16

een a high demand for treatment options for this chronic, urdensome condition that impacts a signifcant population hat demand is li ely to translate to demand for ne ly launched therapies as they ecome availa le Additionally, there may e an increase in patients seeking diagnosis as therapy options expand and awareness of the disease and opportunities for treatment gro he maret gro th for AD is pro ected to increase to illion y

Dupiluma is currently dominant in the AD space, and it may ta e time for this to ad ust as ne agents enter the mar et Payers ill li ely strategize to ensure proper use of and access to these

ne to mar et therapies Since there is potential for o la el use of dupiluma and ne ly launched therapies, prior authorization may e ey in ensuring appropriate use Additionally, step therapy may e employed, ith lo cost topicals and preferred rands or iologics as re uired steps his e pansive pipeline carries the promise of a roader AD mar et, hich may lead to more e i ility for payers to negotiate costs and management strategies

References

czema Atopic Dermatitis National Institute of Allergy and Infectious Diseases, Apr , https niaid nih gov diseases conditions eczema atopic dermatitis

Avena oods, Carmela Overvie of Atopic Dermatitis AJMC Supplement, une , https a mc com vie overvie of atopic dermatitis article

ichenfeld, a rence, et al Guidelines of care for the management of atopic dermatitis section Diagnosis and assessment of atopic dermatitis Journal of the American Academy of Dermatology, Nov , https pu med nc i nlm nih gov

llis, N C , et al Understanding and managing atopic dermatitis in adult patients Seminars in Cutaneous Medicine and Surgery, 2012, suppl S S doi sder

czema ypes Atopic Dermatitis Symptoms American Academy of Dermatology Association, https aad org pu lic diseases eczema types atopic dermatitis symptoms

Cra ford, Mali , et al CPI Detailed eport Data for Septem er U.S. Bureau of Labor Statistics, Sept , https fraser stlouisfed org fles docs pu lications cpidr cpi pdf

Druc er, Aaron, et al he Burden of Atopic Dermatitis Summary of a eport for the National czema Association Journal of Investigative Dermatology, an , https sciencedirect com science article pii S fn

Chamlin, Sarah, et al ects of atopic dermatitis on young American children and their families Pediatrics, Sept , https pu med nc i nlm nih gov

Holm, A , et al ife uality assessment among patients ith atopic eczema British Journal of Dermatology, Apr , https pu med nc i nlm nih gov

Bei ert, F C , et al illingness to pay and uality of life in patients ith atopic dermatitis Archives of Dermatological Research, Apr , https pu med nc i nlm nih gov

Misery, , et al Atopic dermatitis impact on the uality of life of patients and their partners Dermatology, , https pu med nc i nlm nih gov

Atopic dermatitis eczema Mayo Clinic, https mayoclinic org diseases conditions atopic dermatitis eczema diagnosis treatment drc

FDA approves DUPI N ® dupiluma for moderate to severe atopic dermatitis in adolescents Regeneron, Mar , https investor regeneron com ne s releases ne s release details fda approves dupi entr dupiluma moderate severe atopic

Atopic Dermatitis Clinical Guideline American Academy of Dermatology Association, , https aad org mem er clinical uality guidelines atopic dermatitis

Atopic dermatitis A practice parameter update American Academy of Allergy, Asthma, & Immunology, , https pu med nc i nlm nih gov

IPD Analytics Atopic Dermatitis

Siegfried, laine, et al ects of variations in access to care for children ith atopic dermatitis BMC Dermatology, Dec , https mcdermatol iomedcentral com articles s

Minemyer, Paige Optum hy payers should e atching urry of drug development activity around eczema Fierce Healthcare, May , https fercehealthcare com payer optum hy payers should e atching urry drug development activity around eczema

In the treatment of adults with active lupus nephritis…

START WITH A STRONG FIRST LINE

Indications

LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (LN). Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation.

Important Safety Information

BOXED WARNINGS: MALIGNANCIES AND SERIOUS INFECTIONS

Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death.

CONTRAINDICATIONS: LUPKYNIS is contraindicated in patients taking strong CYP3A4 inhibitors because of the increased risk of acute and/or chronic nephrotoxicity, and in patients who have had a serious/severe hypersensitivity reaction to LUPKYNIS or its excipients.

WARNINGS AND PRECAUTIONS

Lymphoma and Other Malignancies:

Immunosuppressants, including LUPKYNIS, increase the risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to

increasing doses and duration of immunosuppression rather than to the use of any specific agent.

Serious Infections: Immunosuppressants, including LUPKYNIS, increase the risk of developing bacterial, viral, fungal, and protozoal infections (including opportunistic infections), which may lead to serious, including fatal, outcomes.

Nephrotoxicity: LUPKYNIS, like other calcineurin inhibitors (CNIs), may cause acute and/or chronic nephrotoxicity. The risk is increased when CNIs are concomitantly administered with drugs associated with nephrotoxicity.

Hypertension: Hypertension is a common adverse reaction of LUPKYNIS therapy and may require antihypertensive therapy.

Neurotoxicity: LUPKYNIS, like other CNIs, may cause a spectrum of neurotoxicities: severe include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremor, paresthesia, headache, and changes in mental status and/or motor and sensory functions.

Hyperkalemia: Hyperkalemia, which may be serious and require treatment, has been reported with CNIs, including LUPKYNIS. Concomitant use of agents associated with hyperkalemia may increase the risk for hyperkalemia.

Using LUPKYNIS™ (voclosporin) in combination with MMF and steroids can transform your first-line regimen1,a,b

Significantly greater complete renal response rates with LUPKYNIS vs standard of care alone

Faster proteinuria reductions than standard of care alone

Outcomes achieved with a low-dose steroid regimen

Novel CNI with no drug level monitoring required1,2

aComplete renal response was achieved in 40.8% of patients with LUPKYNIS and 22.5% with control. Proteinuria reductions (UPCR ≤0.5 mg/mg) were achieved at a median time of 169 days with LUPKYNIS vs 372 days with control.1

bComplete renal response was defined as a confirmed UPCR of ≤0.5 mg/mg; eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of >20% or no treatment- or disease-related eGFR-associated event at time of assessment; presence of sustained, low-dose steroids (≤10 mg prednisone from Weeks 44-52); and no administration of rescue medications. Proteinuria reduction was based on time to UPCR of ≤0.5 mg/mg.1

CNI=calcineurin inhibitor; eGFR=estimated glomerular filtration rate; MMF=mycophenolate mofetil; standard of care=MMF + steroids; UPCR=urine protein/creatinine ratio.

QTc Prolongation: LUPKYNIS prolongs the QTc interval in a dose-dependent manner when dosed higher than the recommended lupus nephritis therapeutic dose. The use of LUPKYNIS in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongation.

Immunizations: Avoid the use of live attenuated vaccines during treatment with LUPKYNIS. Inactivated vaccines noted to be safe for administration may not be sufficiently immunogenic during treatment with LUPKYNIS.

Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another CNI immunosuppressant. If PRCA is diagnosed, consider discontinuation of LUPKYNIS.

Drug-Drug Interactions: Avoid co-administration of LUPKYNIS and strong CYP3A4 inhibitors or with strong or moderate CYP3A4 inducers. Reduce LUPKYNIS dosage when co-administered with moderate CYP3A4 inhibitors. Reduce dosage of certain P-gp substrates with narrow therapeutic windows when co-administered.

ADVERSE REACTIONS

The most common adverse reactions (≥3%) were glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection,

abdominal pain upper, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite.

SPECIFIC POPULATIONS

Pregnancy/Lactation: May cause fetal harm. Advise not to breastfeed.

Renal Impairment: Not recommended in patients with baseline eGFR ≤45 mL/min/1.73 m2 unless benefit exceeds risk. If used in this population, reduce LUPKYNIS dose.

Hepatic Impairment: For mild or moderate hepatic impairment, reduce LUPKYNIS dose. Avoid use with severe hepatic impairment.

Please see Brief Summary of Prescribing Information including Boxed Warning on adjacent pages.

References: 1. LUPKYNIS [package insert]. Rockville, MD: Aurinia Pharma U.S., Inc., 2021. 2. Kuglstatter A, Mueller F, Kusznir E, et al. Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin). Acta Crystallogr D Biol Crystallogr. 2011;67(pt 2):119-123.

LUPKYNISTM (voclosporin) capsules, BRIEF SUMMARY

SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION

BOXED WARNINGS: MALIGNANCIES AND SERIOUS INFECTIONS

Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death.

INDICATIONS AND USAGE

LUPKYNIS is indicated with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (LN). Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation.

CONTRAINDICATIONS

LUPKYNIS is contraindicated in patients taking strong CYP3A4 inhibitors because these medications can significantly increase exposure to LUPKYNIS, which may increase the risk of acute and/or chronic nephrotoxicity, and in patients who have had a serious/severe hypersensitivity reaction to LUPKYNIS or its excipients.

WARNINGS AND PRECAUTIONS

Lymphoma and Other Malignancies: Immunosuppressants, including LUPKYNIS, increase the risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent.

Serious Infections: Immunosuppressants, including LUPKYNIS, increase the risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. These infections may lead to serious, including fatal, outcomes. Viral infections reported include cytomegalovirus and herpes zoster infections.

Nephrotoxicity: LUPKYNIS, like other calcineurin inhibitors (CNIs), can cause acute and/or chronic nephrotoxicity. The risk is increased when CNIs are concomitantly administered with drugs associated with nephrotoxicity. Consider the risks and benefits of LUPKYNIS treatment in light of the patient’s treatment response and risk of worsening nephrotoxicity, including in the following situations:

1) Longer treatment duration beyond one year. Safety and efficacy of LUPKYNIS have not been established beyond one year.

2) Co-administration with drugs associated with nephrotoxicity. The risk for acute and/or chronic nephrotoxicity is increased when LUPKYNIS is concomitantly administered with drugs associated with nephrotoxicity.

Hypertension: Hypertension is a common adverse reaction of LUPKYNIS therapy and may require antihypertensive therapy.

Neurotoxicity: Like other CNIs, LUPKYNIS can cause neurotoxicities. The most severe ones include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremor, paresthesia, headache, mental status changes, and changes in motor and sensory functions.

Hyperkalemia: Hyperkalemia, which may be serious and require treatment, has been reported with CNIs including LUPKYNIS. Concomitant use of agents associated with hyperkalemia may increase the risk for hyperkalemia.

QTc Prolongation: LUPKYNIS prolongs the QTc interval in a dosedependent manner after single dose administration at a dose higher than the recommended lupus nephritis therapeutic dose. The use of LUPKYNIS in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongation.

Immunizations: Avoid the use of live attenuated vaccines during treatment with LUPKYNIS. Inactivated vaccines noted to be safe for administration may not be sufficiently immunogenic during treatment with LUPKYNIS.

Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another CNI immunosuppressant. If PRCA is diagnosed, consider discontinuation of LUPKYNIS.

ADVERSE REACTIONS

Clinical Trials Experience

A total of 355 patients with LN were treated with voclosporin in the Phase 2 and 3 clinical studies of whom 224 were exposed for at least 48 weeks. A total of 267 patients received at least 1 dose of LUPKYNIS 23.7 mg twice a day with 184 exposed for at least 48 weeks. A total of 88 patients received at least 1 dose of voclosporin 39.5 mg twice a day with 40 exposed for 48 weeks. Patients received background treatment with MMF 2 g daily and an IV bolus of corticosteroids followed by a pre-specified oral corticosteroid taper dosing schedule.

Adverse Reactions in ≥3% of Patients Treated with LUPKYNIS 23.7 mg BID and ≥2% Higher than Placebo in Studies 1 and 2

Adverse Reaction

filtration rate (GFR) decreased*

*GFR decreased was the most frequently reported renal adverse reaction. Other renal adverse reactions were renal impairment, acute kidney injury, blood creatinine increased, azotemia, renal failure, oliguria, and proteinuria.

Other adverse reactions reported in less than 3% of patients in the LUPKYNIS 23.7 mg group and at a 2% higher rate than in the placebo group through Week 48/52 included gingivitis and hypertrichosis. Studies 1 and 2 were integrated to represent safety through 48/52 weeks for placebo (n=266), LUPKYNIS 23.7 mg twice a day (n=267), and voclosporin 39.5 mg twice a day (n=88). Exposure adjusted incidence rates were adjusted by study for all the adverse events reported in this section.

DRUG INTERACTIONS

Effect of Other Drugs on LUPKYNIS

Strong and Moderate CYP3A4 Inhibitors: Voclosporin is a sensitive CYP3A4 substrate. Co-administration with strong or moderate CYP3A4 inhibitors increases voclosporin exposure, which may increase the risk of LUPKYNIS adverse reactions. Co-administration of LUPKYNIS with strong CYP3A4 inhibitors (e.g., ketoconazole,

itraconazole, clarithromycin) is contraindicated. Reduce LUPKYNIS dosage when co-administered with moderate CYP3A4 inhibitors (e.g., verapamil, fluconazole, diltiazem). Avoid food or drink containing grapefruit when taking LUPKYNIS.

Strong and Moderate CYP3A4 Inducers: Voclosporin is a sensitive CYP3A4 substrate. Co-administration with strong or moderate CYP3A4 inducers decreases voclosporin exposure, which may decrease the efficacy of LUPKYNIS. Avoid co-administration of LUPKYNIS with strong or moderate CYP3A4 inducers.

Effect of LUPKYNIS on Other Drugs

Certain P-gp Substrates

Voclosporin is a P-gp inhibitor. Co-administration of voclosporin increases exposure of P-gp substrates, which may increase the risk of adverse reactions of these substrates. For certain P-gp substrates with a narrow therapeutic window, reduce the dosage of the substrate as recommended in its prescribing information, if needed.

OATP1B1 Substrates

The effect of LUPKYNIS on OATP1B1 substrates (e.g., statins) has not been studied clinically. However, voclosporin is an OATP1B1 inhibitor in vitro, and information suggests an increase in the concentration of these substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when used concomitantly with LUPKYNIS.

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

Avoid use of LUPKYNIS in pregnant women. The available data on the use of LUPKYNIS in pregnant patients are insufficient to determine whether there is a drug associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with systemic lupus erythematosus (SLE). LUPKYNIS may be used in combination with a background immunosuppressive therapy regimen that includes mycophenolate mofetil (MMF). MMF used in pregnant women and men whose female partners are pregnant can cause fetal harm (major birth defects and miscarriage). Refer to the MMF prescribing information for more information on its use during pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk: Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal LN increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block.

Lactation

There are no available data on the presence of voclosporin in human milk, the effects on the breastfed infant, or the effects on milk production. Voclosporin is present in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Given the serious adverse reactions seen in adult patients treated with LUPKYNIS such as increased risk of serious infections, advise patients that breastfeeding is not recommended during treatment and for at least 7 days after the last dose of LUPKYNIS (approximately 6 elimination half lives).

Females and Males of Reproductive Potential LUPKYNIS may be used in combination with a background immunosuppressive therapy regimen that includes MMF. If LUPKYNIS is administered with MMF, the information for MMF regarding pregnancy testing, contraception, and infertility also applies to this combination regimen. Refer to MMF prescribing information for additional information.

Pediatric Use: The safety and efficacy of LUPKYNIS in pediatric patients has not been established.

Geriatric Use: Clinical studies of LUPKYNIS did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Impairment

Use of LUPKYNIS is not recommended in patients with a baseline e 45 mL/min/1.73 m2 unless the benefit exceeds the risk. If used in patients with severe renal impairment at baseline, LUPKYNIS should be used at a reduced dose. No dosage adjustment is recommended in patients with mild or moderate renal impairment at baseline. Monitor e closely. After initiating therapy, dosing adjustments should be made based on eGFR.

Hepatic Impairment

Reduce LUPKYNIS dosage in patients with mild/moderate hepatic impairment. Avoid LUPKYNIS in patients with severe hepatic impairment.

OVERDOSAGE

Symptoms of accidental overdose may include tremor, headache, nausea and vomiting, infections, tachycardia, urticaria, lethargy, and increases in blood urea nitrogen, serum creatinine, and alanine aminotransferase levels. General supportive measures and symptomatic treatment are recommended in cases of overdose.

To report SUSPECTED ADVERSE REACTIONS, contact Aurinia Pharma U.S. Inc. at 1 33 672 2 or DA at 1 DA 1 or www.fda.gov/medwatch

This brief summary is based on LUPKYNIS Prescribing Information (FPI-0009) issued January 2021.

Additional information can be found at LUPKYNIS ro.com.

LUPKYNIS is a trademark of Aurinia Pharmaceuticals Inc. ©2021 Aurinia Pharma U.S., Inc. All Rights Reserved. US-VCS-2100149 03/21

Lupus and Lupus Nephritis:

Advances in reatment and Management

After years of dormancy, the lupus and lupus nephritis pipelines are gro ing, representing hope for patients and management challenges for payers

Martin Burruano, R.Ph. VP, Pharmacy Services Independent Health

upus is an autoimmune disease that currently a ects a out million Americans, of hom are omen 1 upus is more prevalent among omen of color, and Blac patients ith lupus are more li ely to e perience organ system involvement 1

he most common form of lupus is systemic lupus erythematosus S , hich accounts for appro imately of all cases in half of S cases, tissue or ma or organs such as the heart, lungs, id neys, or rain ill e impacted y the disease 1 he other three forms of lupus are cutaneous lupus, drug induced lupus, and neonatal lupus One third of patients ith lupus report having a comor id autoimmune disorder Genetics can play a role in the development of lupus of patients ith lupus have a parent or si ling ho has developed or ill develop lupus 1

Diagnosis and Complications

Diagnosis can e challenging, as many symptoms of S can mimic those of a variety of other ill nesses It ta es an average of si years for patients ith S to e correctly diagnosed of surveyed patients ith S report eing incorrectly diagnosed, and report seeing at least four di erent healthcare providers prior to receiving an accurate diagnosis 1

hile symptoms of S can vary idely, some of the most common symptoms include oint pain and s elling, headaches, severe fatigue, a signature rash on the chee s and nose, hair loss, anemia, lood clots, fever ith no cause, and aynaud s phenomenon hen S a ects internal organs, other symptoms can arise, depending on hich organ is eing impacted 1

In patients ith S , a type of idney disease can develop no n as lupus nephritis 2 In adults ith S , to ill develop lupus nephritis Symptoms can include foamy urine, edema, and high lood pressure upus nephritis can e diagnosed through urine tests, lood tests, and a idney

iopsy 2 An estimated to of patients ith lupus ne phritis ill develop idney failure In patients ith the most severe form of lupus nephritis, called di use proliferative glomerulonephritis, permanent scars form on the idneys, and as scars develop, idney function declines upus nephritis is associated ith other ris s, including a higher ris for cancer specifcally B cell lymphoma and heart and lood vessel issues 2

Current Treatment Landscape for Lupus

Proper treatment for S re uires management y a rheumatologist or rheumatology team , reatment often varies from patient to patient, and treatment regimens can change depending on the symptoms a patient e periences Some treatment options include NSAIDs, steroids, immunosup pressive medications, DH A, and antimalarial drugs such as hydro ychloro uine ,

Anifrolumab (SAPHNELO™)5

In August, the FDA approved anifroluma SAPHN O™ , Astra eneca for the treatment of moderate to severe lupus in adult patients ho are receiving standard therapy Anifroluma ,

Since December 2020, the U.S. Food and Drug Administration has approved two therapies indicated for the treatment of adult patients with active lupus nephritis.

an intravenous monoclonal anti ody treatment, is the frst approved type I interferon receptor antagonist and the frst ne lupus therapy approved in more than a decade he SAPH N O clinical development program, hich included t o phase three U IP trials and the phase t o MUS trial, demonstrated efcacy and safety more patients treated ith anifroluma e perienced a reduction in overall disease activity across organ systems and achieved sustained reduction in oral corticoste roid use compared to the place o Common adverse reactions o served in the clinical trials included nasopharyngitis, upper respiratory tract infection, ronchitis, infusion related reactions, herpes zoster, and cough

Current Treatment Landscape for Lupus Nephritis

hough lupus nephritis is a common progression of S , there as no treatment specifcally indicated for it until late Providers ould typically aim to reduce in ammation in the id neys and decrease overall immune system activity 2 The treat ments used ere not e ective in preventing ne ares or induc ing remission Since Decem er , the U S Food and Drug Administration FDA has approved t o therapies indicated for the treatment of adult patients ith active lupus nephritis

Voclosporin (LUPKYNIS™)7, 8

In anuary , the FDA approved voclosporin UP NIS™ , Aurinia Pharmaceuticals in com ination ith a ac ground immunosuppressive therapy regimen for the treatment of adult patients ith active lupus nephritis Voclosporin is a calcineurin inhi itor and the frst and only FDA approved oral therapy for

LUPUS AND LUPUS NEPHRITIS

lupus nephritis he phase three AU O A trial and phase t o AU A V trial ere used to assess efcacy In the trials, adult patients ith iopsy confrmed lupus nephritis ere random ized to receive either voclosporin or a place o alongside their standard therapy, ith oth groups of patients receiving con current mycophenolate mofetil After months, voclosporin ith standard therapy as more than t o times as e ective as standard therapy alone at achieving complete renal response he group receiving voclosporin e perienced reduction in urine protein creatinine ratio t ice as fast as the place o group, and a higher proportion achieved complete renal response at ee s compared to the place o group Side e ects associ ated ith voclosporin included decreased glomerular fltration rate, hypertension, diarrhea, headache, anemia, urinary tract infection, upper a dominal pain, dyspepsia, alopecia, renal im pairment, a dominal pain, mouth ulcers, fatigue, tremor, acute idney in ury, and decreased appetite

Belimumab (BENLYSTA)10

he FDA approved elimuma B N S A, Gla oSmith line in Decem er as the frst treatment for adults ith lupus nephritis Belimuma is an intravenous infusion monoclonal anti ody esults from the B ISS N study, hich involved patients randomized to receive either elimuma or a place o plus standard therapy, supported efcacy A signifcantly greater num er of patients receiving elimuma achieved primary ef cacy renal response at t o years compared to the place o group he group receiving elimuma had a higher rate of achieving ma or secondary endpoints, including complete renal response and time to renal related event or death, compared to the pla ce o group Adverse reactions associated ith elimuma in cluded fatal infections, nausea, diarrhea, pyre ia, nasopharyn gitis, ronchitis, insomnia, e tremity pain, depression, migraine, pharyngitis, cystitis, leu openia, and viral gastroenteritis

Table 1. Lupus and Lupus Nephritis Pipeline9

In January 2021, the FDA approved voclosporin (LUPKYNIS™, Aurinia Pharmaceuticals) in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis.

Cost Assessment

In a cost utility analysis, voclosporin in com ination ith stan dard care for lupus nephritis demonstrated accepta le cost e ectiveness in comparison to standard care alone, and voclosporin demonstrated more health enefts at a lo er cost hen compared ith the one other FDA indicated treatment for lupus nephritis

he Institute for Clinical and conomic evie IC assessed the comparative clinical e ectiveness and value of oth voclosporin and elimuma for the treatment of lupus nephritis 11 IC re ported that hile there is su stantial uncertainty regarding long term use and outcomes, the drugs oth appear to e priced ith in the recommended health eneft price enchmar ranges he fnal policy recommendation from IC noted that payers should design coverage criteria that do not narro coverage from the FDA la el 1 IC has not yet revie ed anifroluma

Payer Management

After a slo period regarding ne therapies in this space, the cat egory is seeing an in u of ne approved and pipeline therapies for S and lupus nephritis ith gro ing competition in the lupus nephritis category, here there ere previously no FDA approved therapies, payers should anticipate an increase in associated

costs Strategic policy development ill e crucial to managing costs and ensuring appropriate access to treatment Considering the high cost of these therapies and this specialty disease state, prior authorization may e a ey tool for ensuring that patients meet clinical criteria and for managing costs Voclopsorin and elimuma have di erent routes of administration hich may e a consideration in terms of policy development and sites of care, as elimuma is administered intravenously Considering the additional agents in the pipeline for lupus nephritis, guidelines recommending place in therapy for these ne options may e a valua le resource for payers in supporting policy development or prior authorization criteria he promising S and lupus nephritis pipeline presents e citing ne options for this patient population to improve outcomes, ut it ill re uire thoughtful strategizing y payers to ensure e ective management

MRx PIPELINE

References

upus facts and statistics Lupus Foundation of America, Oct , https lupus org resources lupus facts and statistics

upus and idney Disease upus Nephritis National Institute of Diabetes and Digestive and Kidney Diseases, an , https nidd nih gov health information idney disease lupus nephritis

Medications used to treat lupus Lupus Foundation of America, Aug , https lupus org resources medications used to treat lupus

upus Medications and reatment Options Johns Hopkins Lupus Center, https hop inslupus org lupus treatment lupus medications

Saphnelo anifroluma approved in the US for moderate to severe systemic lupus erythematosus AstraZeneca, Aug , https astrazeneca com media centre press releases saphnelo approved in the us for sle html

Parodis, Ioannis, et al Prediction of prognosis and renal outcome in lupus nephritis Lupus Science & Medicine, Fe , https nc i nlm nih gov pmc articles PMC

magellanrx.com/pipeline

FDA Approves Aurinia Pharmaceuticals UP NIS voclosporin for Adult Patients ith Active upus Nephritis Aurinia, an , https ir auriniapharma com press releases detail fda approves aurinia pharmaceuticals lup ynis

aday, ason FDA approves up ynis, frst ever oral therapy for lupus nephritis Healio News, an , https healio com ne s rheumatology fda approves lup ynis frstever oral therapy for lupus nephritis

IPD Analytics upus Nephritis

FDA approves GS s B N S A as the frst medicine for adult patients ith active lupus nephritis in the US GlaxoSmithKline, Dec , https gs com en g media press releases fda approves gs s enlysta as the frst medicine for adult patients ith active lupus nephritis in the us

Belimuma and Voclosporin for upus Nephritis Final Policy ecommendations Institute for Clinical and Economic Review, Apr , https icer org p content uploads IC upus Nephritis Policy ecommendations pdf

Biosimilar Update and Pipeline

In the seven years since the first biosimilar approval in the U.S., biosimilars have established a presence in the healthcare market. They continue to be a point of interest for all healthcare stakeholders, as there is continued activity and advancement in the space. In July 2021, the U.S. Food and Drug Administration (FDA) approved

the first interchangeable biosimilar insulin product for diabetes, marking a milestone with several other insulin biosimilars in the pipeline. 1

Below, we outline a few recent approvals in the space, as well as biosimilars under FDA review and in phase three trials.

RIABNI™ (rituximab-arrx) Amgen

CLL; GPA; MPA

Hulio (adalimumab-fkjp) Viatris

Table 1. Recent Approvals2

BIOSIMILAR UPDATE AND PIPELINE |

Table

Biosimilars Currently Under FDA Review

adalimumab (biosimilar to AbbVie’s HUMIRA®) Alvotech

rani izuma iosimilar to Genentech’s Lucentis®)

evacizuma iosimilar to Genentech’s Avastin®) Bio-Thera Solutions

adalimumab (biosimilar to AbbVie’s HUMIRA®) Coherus BioSciences

pegflgrastim iosimilar to Amgen’s Neulasta®) Lupin

evacizuma iosimilar to Genentech’s Avastin®)

Amneal Pharmaceuticals

evacizuma iosimilar to Genentech’s Avastin®) Centus BiotherapeuticsAstraZeneca

evacizuma iosimilar to Genentech’s Avastin®)

evacizuma iosimilar to Genentech’s Avastin®)

flgrastim iosimilar to Amgen’s NEUPOGEN®)

Samsung BioepisMerck

Viatris-Biocon

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC IV

neutropenia/leukopenia SQ

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC IV

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC IV

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC IV

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC IV submitted — BLA pending

Amneal Pharmaceuticals neutropenia/leukopenia IV, SQ submitted — BLA pending

flgrastim iosimilar to Amgen’s NEUPOGEN®) Apotex neutropenia/leukopenia SQ submitted — BLA pending

flgrastim iosimilar to Amgen’s NEUPOGEN®)

Tanvex BioPharma neutropenia/leukopenia SQ submitted — BLA pending

insulin aspart (biosimilar to Novo Nordisk’s NovoLog®) Viatris (Mylan) T1DM; T2DM SQ submitted — BLA pending

pegflgrastim iosimilar to Amgen’s Neulasta®) Amneal Pharmaceuticals neutropenia/leukopenia

submitted — BLA pending

pegflgrastim iosimilar to Amgen’s Neulasta®) Apotex neutropenia/leukopenia SQ submitted — BLA pending

pegflgrastim iosimilar to Amgen’s Neulasta®) Fresenius neutropenia/leukopenia SQ submitted — BLA pending

Abbreviations: AMD = age-related macular degeneration; AS = ankylosing spondylitis; CD = Crohn’s disease; CRC = colorectal cancer; JIA = juvenile idiopathic arthritis; IV = intravenous; NSCLC = nonsmall cell lung cancer; PsA = psoriatic arthritis; PSO = psoriasis; RA = rheumatoid arthritis; RCC = renal cell carcinoma; SQ = subcutaneous; T1DM = Type 1 diabetes mellitus; T2DM = Type 2 diabetes mellitus; UC = ulcerative colitis Name

3. Current Phase Three Biosimilar Studies

adalimumab (biosimilar to AbbVie’s HUMIRA®) Fresenius RA; AS; PSO; PsA; JIA; CD; UC SQ phase three

adalimumab (biosimilar to AbbVie’s HUMIRA®) Viatris (Mylan) RA; AS; PSO; PsA; JIA; CD; UC SQ phase three

a i ercept iosimilar to egeneron s A®) Santo; Formycon diabetic macular edema; wet AMD intravitreal phase three

a i ercept iosimilar to egeneron s A®) Viatris (Mylan); Janssen diabetic macular edema; wet AMD intravitreal phase three

a i ercept iosimilar to egeneron s A®) Samsung BioepisBiogen diabetic macular edema; wet AMD intravitreal phase three

denosumab (biosimilar to Amgen’s Prolia®) Novartis osteoporosis/osteopenia SQ phase three

2.

Table

Table 3. Current Phase Three Biosimilar Studies (Continued)

eculizuma iosimilar to Ale ion s SO I IS®) Amgen paroxysmal nocturnal hemoglobinuria IV phase three

etanercept (biosimilar to Amgen’s ENBREL®) Coherus BioSciences RA; polyarticular JIA; AS; PSO; PsA

follitropin alfa (biosimilar to EMD Serono’s Gonal-f®) Finox AG

follitropin alfa (biosimilar to EMD Seron’s Gonal-f®) Allergan

in i ima iosimilar to anssen s MICAD ®) Nichi-Iko RA; AS; PSO; PsA; CD; UC

phase three

three

phase three insulin aspart (biosimilar to Novo Nordisk’s NovoLog®) Sanof

insulin glargine iosimilar to Sanof s antus®) Gan & ee Sandoz T1DM; T2DM

natalizuma iosimilar to Biogen s SAB I®) Novartis MS

phase three rani izuma iosimilar to Genentech s Lucentis®) S ADA Arzneimittel Bausch Health wet AMD

rani izuma iosimilar to Genentech s Lucentis®) Coherus BioSciences wet AMD

rituximab (biosimilar to Genentech’s RITUXAN®) Amgen RA; CLL/SLL; NHL (indolent); ANCAassociated vasculitis

three

phase three

phase three

rituximab (biosimilar to Genentech’s RITUXAN®) Archigen Biotech RA; CLL/SLL; NHL (indolent); ANCAassociated vasculitis IV phase three tocilizuma iosimilar to Genentech s ACTEMRA®) Bio-Thera Solutions RA IV phase three trastuzuma iosimilar to Genentech s Herceptin®) Novartis breast cancer; gastric/ gastroesophageal cancer

phase three trastuzuma iosimilar to Genentech s Herceptin®) Tanvex BioPharma breast cancer; gastric/ gastroesophageal cancer IV phase three ustekinumab (biosimilar to Janssen’s STELARA®) Formycon PSO

SQ phase three ustekinumab (biosimilar to Janssen’s STELARA®) Amgen PSO

phase three ustekinumab (biosimilar to Janssen’s STELARA®) Intas PSO

phase three

Abbreviations: AMD = age-related macular degeneration; ANCA = antineutrophil cytoplasmic antibodies; AS = ankylosing spondylitis; CD = Crohn’s disease; CLL = chronic lymphocytic leukemia; JIA = juvenile idiopathic arthritis; IV = intravenous; MS = multiple sclerosis; NHL = non-Hodgkin lymphoma; PsA = psoriatic arthritis; PSO = psoriasis; RA = rheumatoid arthritis; SLL = small lymphocytic lymphoma; SQ = subcutaneous; T1DM = Type 1 diabetes mellitus; T2DM = Type 2 diabetes mellitus; UC = ulcerative colitis

References

1. “FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes.” U.S. Food and Drug Administration, 28 July 2021, https://www.fda.gov/news-events/press-announcements/fdaapproves frst interchangea le iosimilar insulin product treatment diabetes.

2. “Biosimilar Product Information.” U.S. Food and Drug Administration, 29 July 2021, https://www.fda.gov/drugs/biosimilars/biosimilarproduct-information.

Takeda is a global, R&D-driven biopharmaceutical company committed to discovering and delivering life-changing treatments and vaccines that have a lasting impact on society.

Since our founding in 1781 in a market stall in Osaka, Japan, our values endure by putting patient needs first, building trust with society, strengthening our reputation, and developing the business - in that order.

Alzheimer’s Disease:

Treatment Update and Managed Care Implications

As the number of people living with Alzheimer’s disease increases, collaboration between payers and manufacturers will be key in managing costs, ensuring access, and improving outcomes for patients.

Andrew J. Colby, R.Ph., MBA Senior Director, Clinical Operations Health New England

About 6.2 million Americans over age 65 live with Alzheimer’s disease; 72% are age 75 or older and nearly two-thirds are women. As the population of Americans over age 65 increases, the number of those living with Alzheimer’s will grow proportionately, reaching 12.7 million by 2050.1 According to a 2018 report, total costs of care associated with Alzheimer’s disease are estimated at $277 billion and anticipated to pass $1 trillion by 2050.2

The complex progression of Alzheimer’s disease continues to be researched; it is likely that a signifcant symptom free period occurs in hich damage is occurring in the rain ut the person remains untreated and undiagnosed because there are no symptoms presenting.3 Most patients have late onset Alzheimer s, meaning symptoms frst appear in their mid s, hile the less common early-onset Alzheimer’s causes symptoms to appear between a person’s 30s and mid-60s. Usually, the frst symptoms to appear ill e memory pro lems, ut other early stage symptoms can include other signs of cognitive impairment, such as difculty fnding ords, vision or spatial issues, and impaired reasoning or udgment Patients ill e perience increasing cognitive difculties as Alzheimer s progresses through the several stages — preclinical, mild, moderate, and severe.3 Symptoms associated with each stage can be found in Table 1.

Current Treatment Landscape

Due to the complex nature of Alzheimer’s, it is typically treated with multiple modalities or therapies to improve outcomes.4 While several treatments have been approved by the U.S. Food and Drug Administration (FDA) to help manage Alzheimer’s symptoms, most of these treatments are most benefcial for patients in early or middle stages of disease progression 4 Cholinesterase inhibitors such as

Table 1. Alzheimer’s Symptoms by Disease Stage3

Disease Stage: Mild

Memory loss

Poor judgment leading to bad decisions

Loss of spontaneity and sense of initiative

Taking longer to complete normal daily tasks

Repeating questions

Trouble handling money and paying bills

Wandering and getting lost

Losing things or misplacing them in odd places

Mood and personality changes

Increased anxiety and/or aggression

Disease Stage: Moderate

Increased memory loss and confusion

Inability to learn new things

Difculty ith language and pro lems ith reading, riting, and or ing with numbers

Difculty organizing thoughts and thin ing logically

Shortened attention span

Problems coping with new situations

Difculty carrying out multistep tas s, such as getting dressed

Problems recognizing family and friends

Hallucinations, delusions, and paranoia

Impulsive behavior, such as undressing at inappropriate times or places or using vulgar language

Inappropriate outbursts of anger

Restlessness, agitation, anxiety, tearfulness, and wandering

Repetitive statements or movement; occasional muscle twitches

Disease Stage: Severe

Inability to communicate

Weight loss

Seizures

Skin infections

Difculty s allo ing

Groaning, moaning, or grunting

Increased sleeping

Loss of bowel or bladder control

galantamine, rivastigmine, and donepezil are commonly prescribed for mild to moderate Alzheimer’s symptoms as they can provide some reduction or management of cognitive and behavioral symptoms.4

Moderate to severe Alzheimer’s is often treated with memantine, an N-methyl D-aspartate antagonist, which can decrease symptoms, potentially enabling some patients to maintain daily functions longer than they would without this treatment. Other FDA-approved drugs include donepezil, rivastigmine, and a combination therapy of memantine and donepezil.4 Since Alzheimer’s is often associated with a variety of behavioral symptoms, attempts to manage these symptoms with behavioral health interventions are encouraged prior to the use of pharmacotherapy for symptom management.4

Aducanumab (ADUHELM®)

In June, the FDA approved aducanumab (ADUHELM®, Biogen) for the treatment of Alzheimer’s via the accelerated approval pathway. 5 Aducanumab is a monoclonal antibody administered as a once-monthly intravenous infusion; it is the frst ne treatment indicated for Alzheimer s in years and the frst therapy that targets the fundamental pathophysiology of the disease. 5 fcacy as evaluated in t o phase three clinical trials. One trial met the primary endpoint showing primary reduction in clinical decline, while the second trial did not meet the primary endpoint. In the former trial, patients treated ith aducanuma had signifcant dose and time-dependent reduction of amyloid beta plaque, while control patients had no reduction. There is a warning of amyloidrelated imaging abnormalities associated with aducanumab treatment, as well as hypersensitivity reactions, headache, falls, diarrhea, confusion, delirium, and disorientation.

ALZHEIMER’S

Drug

donepezil (Adlarity)

Corium TD

lumateperone tosylate (CAPLYTA®) Intra-Cellular Therapies oral

acetylcholinesterase inhibitor pending

atypical antipsychotic pending (12/17/2021) gantenerumab

Genentech; Roche SQ amyloid-β protein inhibitor phase three lecanemab (BAN2401)

semaglutide (RYBELSUS®)

Biogen; Eisai IV

amyloid-β protein inhibitor phase three

Novo Nordisk; Emisphere Technologies oral glucagon-like peptide-1 agonist phase three

ALZ-801 Alzheon oral amyloid-β protein inhibitor phase three methylthioninium (LMTX™)

TauRx Pharmaceuticals oral second-generation tau protein aggregation inhibitor phase three

masitinib AB Science oral receptor TKI phase three

bupropion + dextromethorphan (AXS-05) Axsome Therapeutics oral NDRI phase three COR388 Cortexyme oral Kgp inhibitor phase three cromolyn + ibuprofen (ALZT-OP1) AZTherapies inhalation NSAIDs phase three sodium oligomannate (GV-971) Shanghai Green Valley oral microbiome therapy phase three NE3107 Neurmedix oral anti in ammatory agent phase three donanemab Eli Lilly and Company IV TBD phase two tilavonemab (ABBV-8E12) AbbVie IV anti-tau antibody phase two

xanamem Actinogen Medical oral 11beta-hydroxysteroid dehydrogenase type 1 phase two (developing) canakinumab (ILARIS®) Novartis SQ IL-1 antagonist phase two vafdemstat O Oryzon Genomics oral LSD1 inhibitor phase two (developing)

A reviations I interleu in IV intravenous gp gingipain SD lysine specifc demethylase ND I norephinephrine dopamine reupta e inhi itor NSAIDs nonsteroidal anti in ammatory drugs S su cutaneous D transdermal I tyrosine inase inhi itor

As aducanumab was approved via an accelerated approval pathway, Biogen must conduct a new randomized, controlled clinical trial to verify its clinical eneft 5 Following the approval of aducanumab, the FDA released a statement explaining the data from the trial and the decision to grant accelerated approval, as well as residual uncertainties.7 Notably, the Peripheral and Central Nervous System Drugs Advisory Committee did not fnd it reasona le to consider clinical eneft of the one successful trial as primary evidence supporting approval, but the Committee did not discuss the option of accelerated approval. Results from the trial showed that aducanumab was associated with a greater reduction in amyloid beta plaques than the placebo (-0.238 vs. -0.005, respectively); thus, the FDA concluded that this reduction in plaques is reasona ly li ely to result in clinical eneft and ustifed accelerated approval, pending results from a new confrmatory trial 7

The Institute for Clinical and Economic Review issued an evidence report fnding the price range needed to reach standard

cost e ectiveness for aducanuma is , to , this is an 85% to 95% discount from the announced list price.8 A public meeting was held in July with a roundtable of stakeholders to discuss the mismatch between the announced price and valuebased estimates, as well as coverage options and potential designs for the re uired confrmatory trial 8

Impact on Payers

With the approval of aducanumab, health policy experts are calling for the U.S. Centers for Medicare & Medicaid Services (CMS) to issue a national coverage determination (NCD) to avoid any confusion over coverage for the treatment.9 Since a signifcant proportion of the Medicare population could eneft from Alzheimer s treatment, an NCD could potentially provide a clear, evidence-based policy to protect those patients, ensure access where appropriate, and avoid con icting policies upon launch 9 CMS may be waiting to coordinate with the FDA on data collected in the required post-approval trials in order to issue an NCD policy. In an absence of any NCD, a

Table 1. Alzheimer’s Disease Pipeline6

number of plans have made the decision not to cover aducanumab at this point in time, citing lack of evidence of the treatment. Several payers and hospital systems have decided not to initiate use of aducanumab until alternative reimbursement mechanisms are explored. Additionally, questions about aducanumab’s approval have arisen within the FDA and among members of U.S. Congress. This will likely only lead to more hesitation around uptake of the drug.

Considering an anticipated 80% to 90% of the population using aducanuma are e pected to e Medicare enefciaries, the out of poc et cost for patients may e signifcant, as this population is not eligible for many copay assistance programs. Payers ill have to e ectively develop criteria and strategize to ensure that patients receiving aducanuma ill clinically eneft from therapy.

Subsequent approvals and multiple novel therapies on the market will require strategic management and policymaking by CMS, as analysts suggest that 96% of the market for these treatments are in the Medicare population. With the accelerated approval of aducanumab, the approval of other pipeline drugs may follow. Cost e ectiveness of ne Alzheimer s treatments is an important starting point for setting value-based prices; performance warranties helping to apportion risk associated with initial treatment can be an important negotiation point for payers and manufacturers.10 As seen in other disease states with innovative therapies, subscription payment plans may be a useful tool to address

CLINICAL ALERT

With the approval of aducanumab, health policy experts are calling for the U.S. Centers for Medicare & Medicaid Services to issue a national coverage determination to avoid any confusion over coverage for the treatment.

a orda ility as novel Alzheimer s therapies enter the mar et 10 Di erent value ased agreements may e a solution for a variety of costly treatment options in the Alzheimer’s space, but they ould re uire efcient care models for screening and treatment in order to e e ective 11 Collaboration between payers and manufacturers will be key in managing costs, ensuring access, and improving outcomes for Alzheimer’s patients.11

References

1. “Facts and Figures.” Alzheimer’s Association, 2021, https://www.alz. org alzheimers dementia facts fgures

2. “Costs Associated With Alzheimer’s Disease Reach $277 Billion Annually, Report Finds.” Administration for Community Living, 20 Mar. 2018, https://acl.gov/news-and-events/news/costs-associatedalzheimers disease reach illion annually report fnds

3. “What Are the Signs of Alzheimer’s Disease?” National Institute on Aging, 16 May 2017, https://www.nia.nih.gov/health/what-are-signsalzheimers-disease.

4. “How Is Alzheimer’s Disease Treated?” National Institute on Aging, 8 July 2021, https://www.nia.nih.gov/health/how-alzheimers-diseasetreated.

5. “FDA Grants Accelerated Approval for Alzheimer’s Drug.” U.S. Food and Drug Administration, 7 June 2021, https://www.fda.gov/newsevents/press-announcements/fda-grants-accelerated-approvalalzheimers-drug.

6. IPD Analytics. “Alzheimer’s disease.”

7. “FDA’s Decision to Approve New Treatment for Alzheimer’s Disease.” U.S. Food and Drug Administration, 7 June 2021, https://www.fda. gov/drugs/news-events-human-drugs/fdas-decision-approve-newtreatment-alzheimers-disease.

8. “Alzheimer’s Disease: An assessment on aducanumab.” Institute for Clinical and Economic Review, July 2021, https://icer.org/assessment/ alzheimers-disease-2021/.

9. Minemyer, Paige. “Experts: CMS should act quickly on a national coverage decision for Biogen’s newly approved Alzheimer’s drug.” Fierce Healthcare, une , https fercehealthcare com payer/experts-cms-should-act-quickly-a-national-coverage-decisionfor-biogen-s-newly-approved.

10. Lin, Pei-Jung, et al. “Preparing the health-care system to pay for new Alzheimer’s drugs.” Alzheimers Dement, Nov. 2020, https://pubmed. ncbi.nlm.nih.gov/32808733/.

11. Hung, Anna, et al. “Addressing Challenges in Payment and Access to Treatments for Early-Stage Alzheimer’s Disease.” Duke Margolis Center for Health Policy, 2020, https://healthpolicy.duke.edu/sites/ default fles du e alzheimerissue rief pdf

Chronic Kidney Disease:

Emerging Therapies and Management Strategies

As the CKD burden increases with disease progression, prevention and slowing of the disease are key to managing costs for a growing population of patients.

Stacy Inman, Pharm.D. Senior Clinical Project Manager Magellan Method

Chronic kidney disease (CKD) occurs in patients whose kidneys have become damaged and do not function as well over time. More than 15% of adults in the U.S. — 37 million people — live with CKD.1 With an estimated 9 in 10 adults with CKD unaware of their condition, the disease remains largely underdiagnosed. CKD is more common in adults over the age of 65 (representing 38%) compared to those ages 45-64 (12%) and 18-44 (6%).1 The most recent data estimate that Medicare costs for CKD totaled more than $81.8 billion in 2018.1 CKD costs are often driven by inpatient admissions, which increase with each progressive stage of CKD, as well as readmissions.2

Type 2 diabetes is the leading cause of CKD and kidney failure in the U.S. Prevention and slowing progression of CKD can be accomplished through successful management of major risk factors, including high blood pressure and high blood sugar levels.3 Since the condition worsens over time and related health problems commonly occur, prevention of CKD is crucial. CKD increases the risk for heart disease and stroke;4 thus, continued management of high blood pressure, blood sugar, and cholesterol levels is important for improved outcomes. Additional health issues associated with C D are anemia and lo red lood cell count e cess uid causing high lood pressure, s elling in the legs, or shortness of breath; weakened immune system; loss of appetite or nausea; decreased sexual response; confusion, problems with memory and thinking, or depression; low calcium levels; and high phosphorus and potassium levels in the blood.4

Another complication from CKD is CKD-associated pruritus, or chronic itching, which occurs in 20% of CKD cases and 40% of end-stage renal disease cases.5 It is commonly attributed to toxin buildup, peripheral neuropathy, immune system dysregulation, or opioid dysregulation.5

As CKD progresses, damage and loss of function can become severe enough to cause kidney failure, at which point dialysis or kidney transplant is necessary for survival.4 Progression to kidney failure, especially in older adults, is more likely if the kidneys are damaged due to poor

management of CKD risk factors. Early detection and proper treatment of CKD can lead to better outcomes and potentially prevent kidney failure.4

Current Treatment Landscape

Treatment for CKD is based on the stage of the disease. Most commonly, a comprehensive treatment plan will include lifestyle modifcations and drug therapy to manage associated health issues such as high blood pressure and cholesterol — and, for patients that progress to end-stage renal disease, dialysis and kidney transplant.

Finerenone (KERENDIA®)6

he FDA approved fnerenone NDIA®, Bayer) in July 2021 for reduction of risk of kidney function decline, kidney failure, cardiovascular death, nonfatal heart attacks, and hospitalization for heart failure in adults with CKD associated with Type 2 diabetes. Finerenone is an oral nonsteroidal selective mineralocorticoid receptor antagonist M A it is the frst MRA and third FDA-approved treatment for CKD in Type 2 diabetes. A randomized, multicenter, double-blind, placebo-controlled study of 5,674 patients with CKD associated with Type 2

With the growing number of older Americans, the number of people living with CKD will continue to increase, making CKD management a priority for strategic management.

dia etes as conducted to evaluate the efcacy of fnerenone Patients received either fnerenone or a place o, and the t o groups were compared for the number of those whose disease progressed to a composite endpoint that included at least 40% reduction in kidney function, progression to kidney failure, or kidney death. A total of 504 of the 2,833 patients who received fnerenone had at least one of the events in the composite endpoint, compared to 600 in the placebo arm. Of the patients who received fnerenone, e perienced cardiovascular death, a nonfatal heart attack, nonfatal stroke, or hospitalization for heart failure, compared to 420 patients in the placebo arm. Treatment ith fnerenone as associated ith hyper alemia, hypotension, and hyponatremia Patients ith adrenal insufciency and those receiving treatment with strong CYP3A4 inhibitors should not ta e fnerenone

Dapaglifozin (FARXIGA®)7

In April , the FDA approved dapagli ozin FA IGA®) oral tablets to reduce risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with CKD at risk for disease progression. This approval mar ed dapagli ozin as the frst sodium glucose transport protein SG inhi itor indicated for C D in patients without Type 2 diabetes. A multicenter, double-blind study of , patients ith C D as conducted to evaluate the efcacy of dapagli ozin Patients received either dapagli ozin or a placebo, and the two groups were compared for the number of patients with disease progression to a composite endpoint, including at least a 50% reduction in kidney function, progression to kidney failure, or cardiovascular or kidney death. Of the patients who received treatment, 197 of the 2,152 had at least one of the composite endpoints compared to 312 of

Drug

empagli ozin A DIANC ®) Boehringer Ingelheim; Eli illy and Company oral

ertugli ozin S G A O Pfzer Merc

semaglutide (Ozempic®) Novo Nordis

diabetic nephropathy CytoDyn

three

phase three

phase three

selonserti GS Gilead oral ASK1 inhibitor phase three

A P D ADP D Tobira Therapeutics; Takeda Pharmaceutical Company oral entry inhibitor phase two

tolvaptan NA U ® suspension) Otsuka oral vasopressin antagonist phase three

bardoxolone methyl Reata Pharmaceuticals oral Nrf path ay activator phase three

lixivaptan Palladio Biosciences oral vasopressin antagonist phase three

tesevatinib (KD019) Kadmon oral receptor TKI phase two

Uremic Pruritus

nalbuphine hydrochloride

Nal uphine Trevi Therapeutics oral opioid agonist; opioid antagonist phase three

difelikefalin (Korsuva (oral)) Cara Therapeutics oral opioid agonist phase two

Abbreviations: ADPKD = autosomal dominant polycystic kidney disease; ARPKD = autosomal recessive polycystic kidney disease; ASK1 = apoptosis signal-regulating kinase 1; CKD = chronic kidney disease; GLP-1 = glucagon-like peptide-1; SGLT2 = sodium-glucose linked transporter 2; TKI = tyrosine kinase inhibitor

the 2,152 patients who received the placebo, and 100 patients who received treatment were hospitalized or died, compared to 138 patients who received the placebo. Adverse reactions associated ith dapagli ozin included Fournier s gangrene, dehydration, serious urinary tract infections, genital yeast infections, and metabolic acidosis or ketoacidosis. Prior to starting treatment ith dapagli ozin, patients should e assessed for their volume status and kidney function and should consider a lower dose of insulin or insulin secretagogue to reduce the risk of hypoglycemia while on treatment.

Difelikefalin

(Korsuva®)9, 10

In August 2021, the FDA approved difelikefalin (Korsuva®, Cara Therapeutics and Vifor Pharma) for treatment of moderate to severe pruritus associated with CKD in adults undergoing

hemodialysis his in ection is a frst in class appa opioid receptor that targets the peripheral nervous system. It was granted priority review by the FDA. Approval was based on evidence presented from two phase three trials. Results from the phase three A M trial sho ed that patients on mcg g of difelikefalin achieved a three-point or greater improvement from baseline in the weekly mean of the daily 24-hour Worst Itch Intensity Numeric ating Scale I N S score at ee , it as 51% compared to 28% for patients on placebo. Additionally, 39% of patients on difelikefalin achieved a four-point or greater improvement in the ee ly mean of I N S score, compared to 18% of placebo patients. Patients on the difelikefalin injection also experienced both a 43% improvement in the average total Skindex-10 score and a 35% improvement in the average total 5-D itch score at week 12. Common adverse reactions reported were diarrhea, dizziness, nasopharyngitis, and vomiting.

Table 1. Chronic Kidney Disease Pipeline8

The U.S. Centers for Medicare & Medicaid Services released e a e del red ce the development of end-stage kidney disease.

Payer Strategies for CKD Management

With the growing number of older Americans, the number of people living with CKD will continue to increase, making CKD a priority for strategic management. Value-based models and care management programs that link providers and payers in an effort to align on improving outcomes and reducing costs seem likely to continue to trend in the CKD space. Data suggest that the cost burden of CKD increases substantially as the disease progresses, causing increased hospitalizations. Slowing disease progression and reducing the need for inpatient admission or readmission may result in cost reduction.2 Studies suggest that there is a high risk of potentially preventable hospitalizations among patients with higher CKD stages; in fact, in one study, nearly 50% of readmissions among patients with CKD were potentially avoidable, as these were most frequently due to diagnoses of heart failure, infection, renal failure, and ischemic heart disease.2, 11, 12 Comprehensive care that e ectively manages CKD, underlying risk factors, and increasing comorbidities is ey to e ectively managing a gro ing population of patients with CKD.2

The U.S. Centers for Medicare & Medicaid Services (CMS) released fve payment models to reduce the development of end stage kidney disease;13 these models are expected to enroll more Medicare patients in arrangements that incentivize providers to prevent CKD and comprehensively manage the health of CKD patients. The CMS Innovation Center released the EndStage Renal Disease Treatment Choices mandatory payment model, which enrolls all dialysis providers in approximately half of the country and provides incentives for at-home dialysis.11 Other models — the Kidney Care First and Comprehensive Kidney Care Contract — remain optional but assess new Medicare payment options with the objective of improving quality of care for CKD patients.13

Several payers have turned to value-based kidney care arrangements, sometimes in partnership with kidney care programs, in an e ort to manage costs and improve outcomes for mem er populations with CKD. BlueCross BlueShield Minnesota and DaVita Integrated Kidney Care entered an agreement comprised of four primary elements:

1. argeted, coordinated care among program sta , nephrologists, and primary care providers.

2. Increasing awareness about CKD in order to catch the disease in its early stages and implement chronic disease management strategies earlier on in disease progression.

3. Use of data analytics as an additional method of identifying at-risk members.

4. Patient education via in-person and virtual channels to ensure proper awareness and understanding of CKD.14

Earlier in 2021, Cigna announced an expansion of its in-home kidney care program for Medicare Advantage members, which consists of regular home visits from care managers to help members living with CKD to manage health, improve outcomes, and reduce hospital admissions.15 Programs such as this one include a comprehensive care management team with case managers, social workers, physicians, nurses, and nephrologists to customize personal care plans, complete with medication therapy and comorbidity management and a focus on social determinants of health.15 Other payers and kidney care centers have announced colla orations as ell, o ering coordinated, holistic care for members with CKD; some of these programs include components such

as expanding care coordination services and transition care units for members recently diagnosed with kidney failure and value-based kidney care agreements.14, 15

he frst approval of an SG inhi itor dapagli ozin to treat C D in patients without Type 2 diabetes is a milestone in the CKD category and creates an opportunity to greatly expand the use of this therapeutic class. Agents in this class are widely covered by payers with minimal restrictions, but payers who manage this class with specifc criteria may revisit and modify their policies ased on labeling expansions to include coverage for CKD patients without Type 2 diabetes. Tools such as step therapy, prior authorization, and uantity limits may e e ective in supporting payer o ectives of managing costs and ensuring proper access to appropriate treatment for a growing CKD population.

he r a r al f a i hi i r da a li i rea

C i a ie i h e diabetes is a milestone in the CKD category and creates an opportunity to greatly expand the use of this therapeutic class.

References

1. “Chronic Kidney Disease in the United States, 2021.” Centers for Disease Control and Prevention, Mar , https cdc gov idneydisease pu lications resources c d national facts html

2. Golestaneh, adan, et al All Cause Costs Increase ponentially with Increased Chronic Kidney Disease Stage.” American Journal of Managed Care, une , https a mc com vie all cause costs-increase-exponentially-with-increased-chronic-kidney-diseasestage-article.

3. “CKD Risk Factors and Prevention.” Centers for Disease Control and Prevention, Mar , https cdc gov idneydisease pu lications resources annual report c d ris prevention html

4. “CKD Related Health Problems.” Centers for Disease Control and Prevention, Mar , https cdc gov idneydisease pu lications resources annual report c d related health pro lems html.

5. Verduzco, Hector Alvarado, et al C D Associated Pruritus Ne Insights Into Diagnosis, Pathogenesis, and Management.” KIREPORTS, May , https doi org e ir

6. “FDA Approves Drug to Reduce Risk of Serious Kidney and Heart Complications in Adults with Chronic Kidney Disease Associated with Type 2 Diabetes.” U.S. Food and Drug Administration, 9 July , https fda gov drugs drug safety and availa ility fda approves-drug-reduce-risk-serious-kidney-and-heart-complicationsadults-chronic-kidney-disease.

7. “FDA Approves Treatment for Chronic Kidney Disease.” U.S. Food and Drug Administration, Apr , https fda gov ne s events press announcements fda approves treatment chronic idney disease.

8. IPD Analytics. “Chronic Kidney Disease.”

9. “FDA approves Korsuva as treatment for pruritus in patients on hemodialysis.” Healio News, Aug , https healio com ne s nephrology fda approves orsuva as treatment for-pruritus-in-patients-on-hemodialysis.

10. Cara herapeutics Announces Positive esults from A M Pivotal Phase 3 Trial of KORSUVATM Injection in Hemodialysis Patients with Pruritus.” Cara Therapeutics, May , https glo ene s ire com ne s release en Cara herapeutics Announces Positive esults From A M 1-Pivotal-Phase-3-Trial-of-KORSUVA-Injection-in-HemodialysisPatients-with-Pruritus.html

11. ie e, Natasha, et al Potentially preventa le hospitalization as a complication of CKD: a cohort study.” American Journal of Kidney Diseases, Aug , https pu med nc i nlm nih gov

12. Donzé, Jacques, et al. “Causes and patterns of readmissions in patients with common comorbidities: retrospective cohort study.” The BMJ, Dec , https doi org m f

13. Co , yan Contri utor Ho Payers Can Be ective in Ne Value Based Models for CKD.” American Journal of Managed Care, 26 Dec. , https a mc com vie contri utor ho payers can e e ective in ne value ased models for c d

14. addill, elsey Payer aunches Value Based idney Care Agreement for CKD, ESKD.” HealthPayer Intelligence, 16 Apr. 2021, https healthpayerintelligence com ne s payer launches value based-kidney-care-agreement-for-ckd-eskd.

15. Nelson, Hannah Payer Boosts MA Chronic idney Management Access, Patient Outcomes.” HealthPayer Intelligence, 15 Mar. 2021, https healthpayerintelligence com ne s payer oosts ma chronic kidney-management-access-patient-outcomes.

Magellan Capability Insight: Enhanced

Utilization Management Program for High-Cost Therapies

A new utilization management program reduces unnecessary healthcare spend.

Brian MacDonald, Pharm.D. Director, Specialty Clinical Strategy Magellan Rx Management

There are 7,000 known rare diseases and less than 10% have FDA-approved therapies. Despite this, orphan drugs are e pected to account for illion in drug spend or one ffth of all prescription sales — by 2024.1 The average cost of an orphan drug continues to rise, especially as more and more orphan drugs enter the market for ultra-rare disease states.1 Combined with increasingly expensive oncology treatments, there are more than medical eneft drugs alone on the mar et ith price tags over $300,000 per year. For example, chimeric antigen receptor T-cell (CAR-T) therapies were considered a cutting-edge treatment a few short years ago, but there are now a handful of options carrying a mean price tag over $400,000. In addition, multiple recent approvals on both the medical and pharmacy enefts to treat other rare diseases such as Duchenne muscular dystrophy and spinal muscular atrophy have average annual costs of over $500,000, all without including the headline-making $2.1 million cost of treatment with onasemnogene abeparvovec-xioi (ZOLGENSMA®).

Payers and patients both face challenges in navigating new treatment options in the rare disease space he surge of high cost drug approvals presents challenges for payers aiming to develop e ective management strategies. Clinical guidelines and literature to establish and support the standard of care for patients impacted by these diseases are often lacking, and appropriate prescribing requires specialized experience.

On the other hand, patients are faced with the burden and potential mental health impact of their rare disease, possible comorbidities, identifying appropriate centers of excellence for treatment, navigating prior authorization and eneft structures ithin their health plans, and direct and nondirect monetary costs associated with their condition and treatment. Care management services may be a potential solution, relieving some of this burden for patients. One study demonstrated a reduction in

The original specialty experts

with proven biosimilar management strategies across high-cost and complex disease categories, including autoimmune and oncology.

hospital readmission rates from 52.6% to 18.4% in diabetic and heart failure patients who participated in an integrated case management program.2 Because medical resource utilization is so high in patients ith comple , rare conditions, a similar eneft could be gained from comprehensive case management services that include holistic team care.

Magellan Rx Management’s Enhanced Utilization Management Program for High-Cost Therapies

As a market leader in specialty drug management on both the pharmacy and medical enefts, e have developed a clinical solution to evaluate these high-cost treatments. Combining enhanced utilization management with access to supportive case management services, Magellan aims to drive optimal outcomes for members who have been prescribed high-cost medication (annual drug costs exceeding $300,000). The program successfully helps payers, medical directors, and provider networks by ensuring appropriate high-cost therapies are prescribed to the right members and avoiding unnecessary costs due to inappropriate use. Members also have access to case management,

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Want to learn more? Connect with us!

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which provides them with high-touch services that a rare or orphan condition may require.

Since early 2020, Magellan has partnered with health plans to embark on this strategy, since cost avoidance due to inappropriate use for ust one mem er ill lead to signifcant annual savings. As a result, clients have already experienced millions of dollars in cost avoidance through high-quality, personalized reviews for members prescribed high-cost therapies for rare and orphan diseases. Magellan is excited to continue to roll out similar strategies for new and existing clients in the near future.

References

1. “Orphan Drug Report 2019: 6th Edition.” Evaluate Pharma, Apr. 2019, https evaluate com sites default fles media do nload fles EvaluatePharma_Orphan_Drug_Report_2019.pdf.

2. McCants, Khalilah, et al. “The Impact of Case Management on Reducing Readmission for Patients Diagnosed With Heart Failure and Diabetes.” Professional Case Management, July/Aug. 2019, https:// pubmed.ncbi.nlm.nih.gov/31145236/.

Magellan Method

AT MAGELLAN METHOD, we are uniquely qualified to solve complex healthcare challenges. As a subsidiary of Magellan Health, a Fortune 500 company, we have access to a wide range of resources and expertise from across our PBM, Medicare, and behavioral health divisions.

We leverage up-to-date healthcare data to implement solutions that transform how care is delivered. Our team of analytic experts partners with you to develop a customized solution that delivers results.

How can we put our Method to work for you?

& Provider Insights

Contact us at MagellanMethod@magellanhealth.com to learn more.

VIEW OUR RESEARCH at magellanrx.com/read to see our insights in action!

Dry Eye Disease:

Changing Treatment and Management Landscape

As the dry eye disease pipeline e pands, preferential formulary tiering, step therapy, and formulary e clusion may all allo patients access to safe and e ective therapies, hile managing costs and ensuring appropriate use.

Lindsay C. Speicher, J.D. Project Manager Magellan Method

Dry eye disease D D is a common, chronic, episodic, multifactorial disease that a ects the tears and ocular surface. The condition is characterized by failure to produce high-quality tears or a suffcient amount of tears to moisturize the eyes 1 he condition can involve tear flm insta ility, inammation, discomfort, visual distur ance, and ocular surface damage 1 The prevalence of DED is not accurately known; estimates range from 5% to 50% and can be as high as 75% among adults over age 40. About 16 to 20 million Americans live with DED, according to various estimates.2, 3, 4 D D is signifcantly less prevalent among adults et een ages and , a ecting only appro imately 2.7% of people in this age range.3, 5 omen are more li ely to e perience D D than men 3, 5

Despite DED’s serious vision and quality-of-life consequences, the condition remains misdiagnosed or undiagnosed and undertreated. A study showed that patients whose DED went undiagnosed and untreated had a signifcant decline in their dry eye related uality of life score untreated D D can often become chronic and progressively more severe.6 D D is diagnosed via a comprehensive e am that includes a refraction evaluation to determine best-corrected visual acuity and assessment of the or ital structures Additional tests to evaluate the cornea and tear flm layer include a slit lamp iomicroscopy e am, a tear flm rea up time test, and the Schirmer s test to measure tear production from the lacrimal glands.3 Symptoms of D D include a scratchy, stinging, or urning feeling in the eyes; red eyes; sensitivity to light; and blurry vision.1 Higher-risk individuals include women, those over the age of 50, those with inadequate intake of vitamin A or omega-3 fatty acids, and those living with certain autoimmune conditions.1 Patients ith D D may e perience an improvement in symptoms by limiting the length of time spent looking at computer screens, tablets, or smartphones. In the long term, if severe DED is undertreated or left untreated, cornea damage can occur.1

he estimated cost to manage a patient ith D D is annually from the payer perspective

DRY EYE DISEASE

Trends to keep an eye on Ophthalmic Injections

Given the high prevalence of DED, the overall cost burden to the U S healthcare system is a out illion 7 Societally, D D carries a burden of $11,302 per patient annually and $55.4 billion overall, including direct and indirect costs.7

DED Treatment

DED is commonly treated with over-the-counter (OTC) eye drops called artifcial tears other O C products such as moisturizing gels and ointments can also provide relief. , There are si FDA approved therapies indicated for D D, three estasis® , Restasis MultiDose®, and CEQUA™) containing cyclosporine as the active ingredient ifestyle modifcations may improve D D symptoms and include avoiding smoke, wind, or air conditioning use of a humidifer limiting screen time earing sunglasses staying hydrated and getting sufcient sleep In addition, medications associated with DED such as antihistamines and tricyclic antidepressants can be adjusted or discontinued to help improve DED symptoms when appropriate. ,

Treatment Guidelines9

Guidelines published by the American Academy of Ophthalmology AAO in note that pharmacological and procedural treatments can be associated with improvements in symptoms and clinical signs of DED. The AAO notes

elimination of e acer ating factors to e one of the frst recommended steps in managing mild DED. With continued symptoms, artifcial tears should e used Prescription drug treatment is recommended for moderate to severe D D specifcally, topical cyclosporine is recommended, has been shown to have clinical eneft, and in some cases can lead to long term treatment free remission for patients iftegrast iidra®), a lymphocyte function associated antigen antagonist, has sho n eneft in signs and symptoms of D D ho ever, long term efcacy and safety are unknown.

Loteprednol etabonate ophthalmic suspension (Eysuvis®)10, 11

In Octo er , the FDA approved loteprednol eta onate ophthalmic suspension (Eysuvis®, ala Pharmaceuticals as the frst ocular corticosteroid for short-term treatment of DED. Approval was granted based on clinical trial results that demonstrated significant improvements in the signs and symptoms of DED. In all phase three trials, statistically signifcant results ere achieved for the endpoint of conjunctival hyperemia after two weeks of dosing. Two of the three phase three trials demonstrated statistical signifcance for the symptom endpoints of ocular discomfort and severity in oth the overall intent to treat I population and in a predefned subgroup of ITT patients with more severe ocular discomfort.

2020 ELEVENTH EDITION

Drug Manufacturer

Route

varenicline (OC-01) Oyster Point Pharma nasal nAChR agonist pending (10/17/2021)

cyclosporine CyclASol®) Novali ophthalmic immunosuppressant phase three

tim etasin GN eGen ree egene Biopharmaceuticals ophthalmic actin modulator; apoptosis inhibitor phase three

tavilermide (MIM-D3) Mimetogen Pharmaceuticals; Allergan ophthalmic TrkA receptor agonist phase three

repro alap AD Aldeyra Therapeutics topical; ophthalmic aldehyde inhibitor phase three

etanercept (HL036) HanAll Biopharma; Daewoong Pharmaceutical ophthalmic NF alpha inhi itor phase three S Mitotech; OraPharma ophthalmic antio idant phase three

per uorohe yloctane NOV Novali Bausch Health ophthalmic lipid layer stabilizer phase three BRM421 BRIM Biotechnology ophthalmic corneal SC stimulator phase three

OmegaD Softgels Omega Pharma oral omega-3 fatty acids and derivatives phase three

tivanisiran sodium S S N IS PharmaMar ophthalmic si NA phase three

A Allysta Pharmaceuticals ophthalmic adiponectin receptor agonist phase three

Abbreviations: LSC = limbal stem cell; nAChR = nicotinic acetylcholine receptor antagonist; siRNA = small interfering RNA; TBD = to be determined; TNF = tumor necrosis factor; TrkA = tropomyosin receptor kinase A

Pipeline

Varenicline (OC-01)

Varenicline (OC-01, Oyster Point Pharma), a nicotinic acetylcholine receptor agonist administered as a nasal spray, is currently under FDA revie for D D In the phase three ONS study of varenicline nasal spray, patients ere randomized to receive one of two doses of varenicline (0.6 mg/mL for 260 patients and 1.2 mg/mL for 246 patients) or a placeo for patients t ice daily for days esults sho ed that the varenicline group e perienced greater improvement in Schirmer s test score a gain of mm or more from the ase -

line y day compared to the place o group hen comparing the two varenicline groups, 47.3% of the 0.6 mg/mL group showed improvement, while 49.2% of the 1.2 mg/mL group sho ed improvement in the place o group, sho ed improvement Both varenicline groups e perienced greater reduction in eye dryness score from the baseline at week 2 compared to the placebo group. The most common adverse reaction reported as sneezing he FDA s decision to approve varenicline nasal spray is e pected on Oct ,

Table 1. DED Expanded Pipeline

Management Strategies

Currently, cyclosporine is the primary prescription agent used in the treatment of DED, and the cyclosporine treatment landscape is set to e pand ith single use estasis ® potentially losing e clusivity in and a ne cyclosporine product in the pipeline, payer management strategies for DED may shift. Ne competition in the D D space may decrease costs, specifically with the launch of generic alternatives. Additionally, the potential approval of varenicline nasal spray alternative therapy may alleviate some of the unmet need in the DED population as this unique route of administration may appeal to DED patients who are averse to self-administering eye drops. Pricing is unknown, but this agent may be priced higher due to its route of administration.

Utilization management strategies will continue to be key in this category Payer tools may help guide patients to ard e ective lower-cost products. Preferential formulary tiering, step therapy, and formulary e clusion may all allo patients access to safe and e ective therapies for D D hile managing costs and ensuring appropriate use. Policy and formulary development should focus on the availability of generics in the coming year.

References

1. “Dry Eye.” National Eye Institute, 22 Dec. 2020, https://www.nei.nih. gov/learn-about-eye-health/eye-conditions-and-diseases/dry-eye.

2. Stapleton, Fiona, et al FOS D S II pidemiology eport The Ocular Surface, July 2017, https://pubmed.ncbi.nlm.nih. gov

3. Rouen, Patricia, and Mary White. “Dry Eye Disease: Prevalence, Assessment, and Management.” Home Healthcare Now, Mar./Apr. , https pu med nc i nlm nih gov

4. “2016 Dry Eye Products Report: A Global Analysis for 2015 to 2021.” Market Scope, 2016.

5. Farrand, im erly, et al Prevalence of Diagnosed Dry ye Disease in the United States Among Adults Aged ears and Older American Journal of Ophthamology, Oct. 2017, https://pubmed.ncbi.nlm.nih. gov

6. amanishi, yutaro, et al Characteristics of Individuals ith Dry ye Symptoms ithout Clinical Diagnosis Analysis of a e Based Survey Journal of Clinical Medicine, 21 May 2019, https://pubmed. ncbi.nlm.nih.gov/31117304/.

7. u, unhua, et al he economic urden of dry eye disease in the United States a decision tree analysis Cornea, Apr. 2011, https:// pubmed.ncbi.nlm.nih.gov/21045640/.

Kenny, Kathleen. “Dry Eye Disease: Higher Rates in View.” Pharmacy Times, 11 May 2017, https://www.pharmacytimes.com/view/dry-eyedisease-higher-rates-in-view.

9. Dry ye Syndrome PPP American Academy of Ophthalmology, Nov , https aao org preferred practice pattern dry eye syndrome ppp

10. ala Pharmaceuticals Announces FDA Approval of SUVIS for the Short erm reatment of the Signs and Symptoms of Dry ye Disease.” BioSpace, 27 Oct. 2020, https://www.biospace.com/article/ releases/kala-pharmaceuticals-announces-fda-approval-of-eysuvisfor-the-short-term-treatment-of-the-signs-and-symptoms-of-dryeye-disease/.

11. FDA approves ysuvis for short term dry eye disease treatment Healio News, 27 Oct. 2020, https://www.healio.com/news/ ophthalmology/20201027/fda-approves-eysuvis-for-shortterm-dryeye-disease-treatment.

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sintilimab Eli Lilly and Company NSCLC (metastatic, EGFR exon 20 insertion mutations) IV BLA March 2022

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A reviations ADHD attention defcit hyperactivity disorder AMD age related macular degeneration ANCA antineutrophil cytoplasmic anti odies AS an ylosing spondylitis B A iologics license application CD Crohn s disease C D chronic idney disease C C colorectal cancer HFr F heart failure ith reduced e ection fraction HIV human immunodefciency virus HSC hematopoietic stem cell transplant; IM = intramuscular; IV = intravenous; JIA = juvenile idiopathic arthritis; NDA = new drug application; NSCLC = non-small cell lung cancer; PAH = pulmonary arterial hypertension; PsA = psoriatic arthritis; PSO = psoriasis; RA = rheumatoid arthritis; RCC = renal cell carcinoma; sBLA = supplemental biologics application; sNDA = supplemental new drug application; SQ = subcutaneous; UC = ulcerative colitis

This information is up to date as of Sept. 20, 2021.