Your Community Health Plan

Big Health Plan Options for Small Groups are Now Available

Groups with 5+ employees, self-funding is possible with Your Community Health Plan.

Big or small, Your Community Health Plan believes that all employers should have health plan options that work for both their employees and their bottom line. Access to an ERISA qualified Level Funded Health Plan is now accessible for groups between 5-100 lives.

Plan options include:

No Cost Primary Care Personal Pharmacist & 300 generic drugs

Plan Protections

Your employees have access under ERISA to Community Care Physician Network, the largest clinicallyintegrated network with 3,000+ primary care providers across NC. In-network primary care visits, including telehealth, are covered at 100% by the plan. The MakoRx network has over 500 locally owned hometown NC pharmacies and 16,000 across the country, all with wholesale direct pricing for all your prescriptions. Giving you a personal pharmacist for guidance and advice. Your Community Health Plan has partnered with The Phia Group for legal representation. Employers gain independent consultation and evaluation, a plan appointed claims evaluator, and a named "Fiduciary". You and your employees have legal counsel in case of surprise billing issues or fraud.

An educational series for ASHP State Affiliates | Join us for a complimentary CPE/CME Webinar!

Getting to Know the New JAKs on the Block:

Pharmacy-Focused Insights for Atopic Dermatitis and Alopecia Areata

Boston University School of Medicine’s Webinar Presentation at:

North Carolina Association of Pharmacists

Date: August 12, 2021 | 12:00 - 1:00pm EDT

Zoom Registration Link:

https://bostonu.zoom.us/meeting/registertJ0qcOiprzgvEtxGxnXfCMPUT0PfcBZsob6f

Learning Objectives

1. Explore the changing paradigm of AA and AD disease presentation and treatment approach. 2. Assess and interpret the latest clinical trial data among emerging oral agents in AA and/or AD and terms of therapeutic target, safety, efficacy, and tolerability. 3. Recognize the potential place in therapy and monitoring aspects for the emerging agents in AD and AA in order to effectively engage patients in shared decision-making for their treatment plan. 4.Outline a plan to proactively identify and remove barriers for health maintenance services and medication access in underserved patients with AA and/or AD.

Target Audience

This curriculum is intended for a broad audience of community pharmacists, dermatologic specialty pharmacists, and managed care professionals involved in the care and treatment of patients with AD and/or AA.

Speakers

Amanuel Kehasse, PharmD

Course Director Clinical Pharmacy Specialist Clinical Pharmacy Specialist in Autoimmune and Interstitial lung disease Boston Medical Center Health System Boston, MA

Peter A Lio, MD

Assistant Professor of Clinical Dermatology and Pediatrics Northwestern Feinberg School of Medicine Director, Chicago Integrative Eczema Center Founding Partner Medical Dermatology Associates of Chicago Chicago, IL

Accreditation

ACPE

The University of Rhode Island College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a

provider of continuing pharmacy education.

This is an application-based educational activity. Pharmacists will receive 1.0 contact hours (0.10 ceus) for the educational activity. No partial credit is available. ACPE Universal Activity Number (UAN): 0060-9999-21-023-L01-P

ACCME

Boston University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Boston University School of Medicine designates this live activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgement

This activity is presented by Boston University School of Medicine and The University of Rhode Island College of Pharmacy and is supported by and independent educational grant from Pfizer.

Scan to Register

Boston University School of Medicine Barry M. Manuel Continuing Medical Education Office

New Drug Monograph

Ponesmiod (Ponvory™)

By: Dr. Nakiya T. Whitfield

In March 2021, the Food & Drug Administration approved ponesimod (Janssen Pharmaceuticals), a sphingosine 1-phosphate (S1P) receptor 1 modulator, similar to Gilenya® (fingolimod), Mayzent® (siponimod), and Zeposia® (ozanimod). Ponesimod is indicated for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. (1) Ponesimod blocks the capacity of lymphocytes to migrate from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which ponesimod exerts therapeutic effects in MS is unknown but may involve reduction of lymphocyte migration into the CNS. (1) Important pharmacokinetic properties about the drug include:

• Absorption: Ponesimod reaches maximum concentration 2-4 hours post dose and has an absolute oral bioavailability of 84% with the 10mg dose. Absorption is not affected by food. • Distribution: Ponesimod is highly bound to plasma proteins (greater than 99%) and is mainly distributed in the plasma fraction of whole blood. It has a volume of distribution of 160 L. • Metabolism: Ponesimod is metabolized extensively by the cytochrome P450 system (CYP2J2, CYP3A4, CYP3A5, CYP4F3A, and CYP4F12). Ponesimod also undergoes direct glucuronidation (UGT1A1 and UGT2B7). • Elimination: Ponesimod has a half-life of 33 Potential concerns related to the use of ponesimod include transient bradycardia, infection, macular edema, elevated transaminase, hypertension, skin malignancies, and respiratory effects such as reduction in FEV1. (1) Clinical Efficacy: Oral Ponesimod Versus Teriflunomide in Relapsing Multiple Sclerosis (OPTIMUM) is the first phase III study to evaluate the efficacy and safety of ponesimod. It was a multicenter, double-blind, active-comparator, superiority randomized control trial that included 1133 patients aged 18 to 55 with multiple sclerosis (MS) with a relapsing course from the onset (relapsing remitting MS or secondary progressive MS). Additional inclusion criteria include an Expanded Disability Status Scale (EDSS) score of 0 to 5.5, and recent clinical or MRI disease activity. (2,3). A few key exclusion points include patients with significant medical conditions or therapies for such (e.g., cardiovascular, pulmonary, immunological, hepatic, ophthalmological, ocular), lactating or pregnant women, or patients with contraindications to MRI. Patients who met eligibility criteria were randomized in a 1:1 fashion to receive teriflunomide 14 mg by mouth once daily or ponesimod 20 mg daily (after following a 14-day dose titration). (4)

The primary endpoint of the study was annualized relapse rate (ARR) based on the number of confirmed relapses per patient year from randomization to the end of the study. A confirmed relapse was defined as a new, worsening, or recurrent neurological symptoms that occurred at least 30 days after onset of preceding relapse, lasted at least 24 hours, and was accompanied by a documented increase in the EDSS score. Safety assessments included treatment emergent adverse events. (2) Treatment with ponesimod reduced ARR by 30.5% compared to teriflunomide (mean ARR, 0.202 vs 0.290; rate ratio, 0.695 [99% CI 0.536-0.902]; P<0.001. Additionally, the proportion of patients who experienced at least one treatment emergent adverse even was similar between the two groups. The most common adverse events in the ponesimod group included a persistently alanine aminotransferase (ALT) at 1 and 15 days after the end of

treatment, nasopharyngitis, headache, and upper respiratory infection, increase in blood pressure, and dyspnea. Overall, adverse events leading to treatment discontinuations were more frequent in the ponesimod group (49 of 565 [8.7%] vs 34 of 566 [6.0%]).(2)

Overall, OPTIMUM showed that ponesimod is superior to teriflunomide on the primary endpoint of ARR. Ponesimod was also well tolerated, and safety results were in line with previous observations in its phase 2 study and other S1P receptor modulators in controlled studies. (2)

Before therapy with ponesimod is initiated, a workup including a complete blood count, liver function tests; ophthalmic evaluation (fundus, including the macula), and echocardiogram should be obtained. Patients with pre-existing cardiac conditions (e.g., bradycardia, first or second-degree AV block, myocardial infarction, or heart failure) should be closely monitored in a clinical setting following the first dose of ponesimod. (1)

Due to the risk of bradycardia, ponesimod should be gradually tapered for the first two weeks of therapy before the standard maintenance dose is achieved. (1)

14-day Starter Pack

Maintenance Dose Titration Day Daily Dose

Days 1 and 2 2 mg Days 3 and 4 3 mg Days 5 and 6 4 mg Day 7 5 mg Day 8 6 mg Day 9 7 mg Day 10 8 mg Day 11 9 mg Day 12, 13, and 14 10 mg Day 15 and beyond 20 mg

For patients with mild hepatic impairment (ChildPugh A) no dose adjustment is needed. However, in patients with moderate to severe liver impairment (Child-Pugh Class B or C), treatment is not recommended. (1) In patients with moderate to severe renal disease, there were no clinically significant changes in the maximum serum concentration or the area under the curve of ponesimod; therefore, no dose adjustments are recommended in those with renal impairment. (1)

Other considerations when considering treatment with ponesimod include:

• Infection - In patients with an active infection, treatment initiation should be delayed until resolution of the infection. If a patient has already begun treatment with ponesimod, consideration for interrupting treatment should be given if a serious infection develops. • Macular edema - If macular edema is diagnosed on ophthalmologic exam, individual risk and benefits should be assessed to determine if therapy should be discontinued.

If a patient misses fewer than 4 consecutive doses during the initial titration, resume treatment with the first missed titration dose and resume the titration schedule. If 4 or more consecutive doses are missed, reinstate treatment with a new starter pack at day 1 and complete first-dose 4-hour ECG monitoring in appropriate patients.

If a patient misses fewer than 4 consecutive maintenance doses, resume treatment with the maintenance dosage. If 4 or more consecutive maintenance doses are missed, reinitiate treatment with a new starter pack at day 1 of the titration regimen and complete first-dose 4-hour ECG monitoring in appropriate patients.

Ponesimod is available in a 14-day starter pack [2 mg, 3 mg, 4 mg (two each); 5 mg, 6 mg, 7 mg, 8 mg, 9 mg (one each); 10 mg (three each)] and as a 20mg tablet. The current average wholesale price of ponesimod is $323.34 per tablet.

Important patient counseling tips should include: (1)

• Ponesimod should be swallowed whole and may be taken with or without food. • Slow heart rate may occur (especially when first starting the medication).

• Ponesimod can increase the risk of infections. Contact the provider if symptoms of infection develop. • Receiving some live vaccines should be avoided while taking ponesimod. Be sure to be current on vaccines before starting therapy with ponesimod. • Follow the titration schedule closely. If doses are missed, consult with the pharmacist or other provider before resuming therapy. Write down the date you start taking ponesimod so it is easier to keep track of any day(s) you miss. • If more than 4 days of therapy is missed (either in the titration or maintenance phase), do not resume therapy without speaking to the provider.

Summary/Use in Clinical Practice: Ponesimod is a once-daily oral selective S1P1 modulator, used to treat adults with relapsing forms of MS including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. (5) Current guidelines for the treatment of MS recommend the use of disease modifying therapies for all people with relapsing forms of MS. (6)

When comparing ponesimod to other S1P receptor modulators, there are several similarities between the agents including the required baseline labs, adverse effects, and once daily dosing. There are also notable differences between the approved agents. For example, fingolimod requires patient observation for 6 hours following the administration of the first dose, whereas with ponesimod, this is only necessary for patients with pre-existing cardiac conditions. (7)

Additionally, unlike siponimod which requires CYP2C9 genotype testing prior to initiating therapy, ponesimod does not have additional requirements. (8)

Ponesimod is unique in that if treatment needs to be stopped, it leaves the blood within one week, with effects on the immune system wearing off in one to two weeks for most patients.This may offer additional flexibility and a distinct advantage in treatment management if patients need to receive vaccines, address potential infections, or begin family planning. (5)

References:

1. Product Information: PONVORY(TM) oral tablets, ponesimod oral tablets. Janssen Pharmaceuticals Inc (per manufacturer), Titusville, NJ, 2021. 2. Kappos L, Fox RJ, Burcklen M, et al. Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator phase 3 optimum study: a randomized clinical trial . JAMA Neurol. 2021;78(5):558. 3. Kappos L, Fox RJ, Burcklen M, et al. Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator phase 3 optimum study: a randomized clinical trial [Supplemental Appendix 1]. JAMA Neurol. 2021;78(5):558. 4. Kappos L, Fox RJ, Burcklen M, et al. Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator phase 3 optimum study: a randomized clinical trial [Supplemental Appendix 2]. JAMA Neurol. 2021;78(5):558. 5. Janssen Announces US FDA Approval of Ponvory (Ponesimod), an Oral Treatment for Adults with Relapsing Multiple Sclerosis Proven Superior to Aubagio (teriflunomide) in Reducing Annual Relapses and Brain Lesions [news release]. Janssen Pharmaceuticals; March 19, 2021.https:// www.janssen.com/us/news-center/press-releases.

Accessed May 25, 2021. 6. Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-Modifying Therapies for Adults with Multiple Sclerosis: Report of the

Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(17):777-788 7. Gilenya (fingolimod) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; December 2019. 8. Mayzent (siponimod) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; January 2021.