VALUE-BASED HIV FORMULARIES by Integritas Communications

VALUE-BASED HIV FORMULARIES Optimizing Use of Clinical Evidence and Pharmacoeconomic Models in Managed Care

Learning Objectives • Discuss the latest efficacy, safety, and clinical and health-care− utilization outcomes data for new and emerging HIV regimens • Describe the effects of key patient, provider, and system-based factors on viral persistence, treatment durability, treatment adherence, and utilization outcomes among patients with HIV • Assess complex cost and quality concerns in HIV management using pharmacoeconomic instruments and strategies • Improve value-based HIV formulary decision-making to reflect recent clinical evidence, best-practice pharmacy utilization processes, and prevailing pharmacoeconomic assessment strategies

Faculty Richard A. Elion, MD

Clinical Professor of Medicine George Washington University School of Medicine Codirector, HIV/HCV Program Providence Hospital Washington, DC

James A. Jorgenson, RPh, MS, FASHP Chief Executive Officer and Board Chair Visante Inc. & Visante Ltd. St. Paul, Minnesota

Robert LoNigro, MD, MS EVP, Clinical Operations Health Care Partners Austin, Texas

Disclosures • Richard A. Elion, MD – Consultant: Gilead Sciences Inc.; Speakers Bureau: Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc.; Honorarium: Gilead Sciences Inc. and Janssen Pharmaceuticals , Inc.; Expert witness: Gilead Sciences, Inc.

• James A. Jorgenson, RRh, MS, FASHP – Consultant at Visante, Inc. and Visante Ltd.; Speaker Bureau at Novartis

• Robert LoNigro, MD, MS – Has nothing to disclose

Evolving Healthcare and HIV-Management Strategies • Universal issues –Access –Affordability –Adherence to therapy

• Global and individual treatment considerations –Clinical –Economic –Regulatory

2017: THE REALITIES OF HIV DISEASE AND CURRENT TREATMENTS Richard A. Elion, MD

Individualizing ART and Its Formulary Implications • Initial regimens • Switch regimens

Topics for Discussion

– Efficacy of simplified 2- vs 3-drug regimens – Efficacy and safety of long-acting 2-drug IM maintenance therapy

• Patient-centered factors – Tolerability – Toxicity – Adherence

• Shorter treatment courses for HCV coinfection • Targeted PrEP strategies for MSM ART, antiretroviral therapy; IM, intramuscular; HCV, hepatitis C virus; PrEP, pre-exposure prophylaxis; MSM, men who have sex with men.

First-Line ART Regimens DHHS and IAS-USA Guidelines DHHS1

Class

Integrase Inhibitor–Based Regimens Should Be Initial Therapy for Most People with HIV • DTG/ABC/3TCa (if HLA-B*5701–negative) • DTG + TDF/FTCa or TAF/FTCa Integrase Inhibitor-Based • EVG/c/TDF/FTC or EVG/c/TAF/FTC • RAL + TDF/FTCa or TAF/FTCa Boosted PI-Basedb

• • • •

DRV/c or DRV/r + TDF/FTCa or TAF/FTCa ATV/c or ATV/r + TDF/FTCa or TAF/FTCa DRV/c or DRV/r + ABC/3TCa (if HLA-B*5701–negative) ATV/c or ATV/r+ ABC/3TCa (if HLA-B*5701–negative and HIV RNA levels are <100,000 copies/mL)

IAS-USA2 • • • •

DTG/ABC/3TCa DTG + TAF/FTC EVG/c/TAF/FTC RAL + TAF/FTC

• No recommendations

/, drugs in combination formulations; +, separate pills in medication regimens; 3TC, lamivudine; ABC, abacavir; ATV, atazanavir; c, cobicistat; DHHS, US Department of Health and Human Services; DRV, darunavir; DTG, dolutegravir; EVG, elvitegravir; FTC, emtricitabine; HLA, human leukocyte antigen; IAS-USA, International Antiviral Society-USA Panel; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; r, ritonavir; RAL, raltegravir; RNA, ribonucleic acid; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate. a3TC may substitute for FTC or vice versa, if a non–fixed-dose NRTI combination is desired; bIn general, boosted DRV is preferred over boosted ATV. 1. DHHS. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living With HIV. 2017. Updated October 17, 2017. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/11/what-to-start. Accessed November 3, 2017; 2. Günthard HF, et al. JAMA. 2016;316(2):191-210.

Immediate/Continuous ART Reduces Various Disease Risks

Combined Analysis of the SMART and START Studies • Complications in the combined study populations (N=10,157) – – – – – –

Hazard Ratios and 95% CIs AIDS

AIDS eventsa (n=123) Serious non-AIDS event Serious non-AIDS eventsb (n=244) Cardiovascular disease Cardiovascular disease (n=103) Cancer Cancer (n=117) Death Death (n=118) AIDS or serious non-AIDS event AIDS and serious 0.5 1.0 non-AIDS events (n=359)

Increased Risks With Interrupted (SMART) or Delayed (START) ART

2.0

5.0

10.0

Immune preservation via immediate and continuous ART significantly reduces risks of AIDS and non-AIDS events AIDS, acquired immunodeficiency virus; CI, confidence interval; ESRD, end-stage renal disease, SMART, Strategies for Management of AntiRetroviral Therapy; START, Strategic Timing of AntiRetroviral Treatment. aAIDS events: death from AIDS, any AIDS-defining event, or Hodgkin lymphoma; bSerious non-AIDS events: cardiovascular disease or death from cardiovascular disease, ESRD or death from ESRD, decompensated liver disease or death from liver disease, non–AIDS-defining cancer (except basal cell or squamous cell skin cancer) or death from cancer, or any death not attributable to AIDS. Borges AH, et al. 24th Conference on Retroviruses and Opportunistic Infections; February 13‒16, 2017; Seattle, WA. Abstract 474.

Transmitted HIV Antiretroviral Drug Resistance

Support for Integrase Inhibitors as First-Line ART Genotypic Resistance Test Resultsa

Resistance, %

30 25

2013

30.2

2014 2015

24.2

22.6

15.9 13.2

10.2

9.9

5.7

4.5

4.4

3.4 0

0 Overall

NRTI

NNRTI

Integrase Inhibitor

NNRTI, nonnucleoside reverse transcriptase inhibitor. a339 genotypic test results from 1060 HIV patients identified as ART-naĂŻve (Stanford University HIV Drug Resistance Database). future research is needed to evaluate transmitted drug resistance for integrase inhibitor in a larger database. Volpe JM, et al. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17â&#x20AC;&#x2019;21, 2015; San Diego, CA. Abstract LB3389.

Integrase Inhibitor vs Boosted PIs

Treatment Failures at Week 96 in ACTG A5257 Study Virologic Failurea

Favors

Atazanavir/r vs raltegravir Darunavir/r vs raltegravir Atazanavir/r vs darunavir/r

Neither Neither Neither

3.4% 5.6% -2.2%

Tolerability Failurea

Favors

Atazanavir/r vs raltegravir Darunavir/r vs raltegravir Atazanavir/r vs darunavir/r

12.7% 3.6% 9.2%

Virologic or Tolerability Failurea

Raltegravir Neither Darunavir/r

Favors

Atazanavir/r vs raltegravir Darunavir/r vs raltegravir Atazanavir/r vs darunavir/r

14.9% 7.5% 7.5% -20

-10

Raltegravir Raltegravir Darunavir/r

Pairwise Difference in Cumulative Incidence at Week 96 (97.5% CI) N=1809 treatment-naĂŻve patients with HIV RNA levels >1000 copies/mL randomized to emtricitabine/TDF with atazanavir/r, raltegravir, or darunavir/r. aEquivalence predefined as 2-sided 97.5% CI on pairwise differences in 96-week cumulative incidence of each endpoint falling within â&#x2C6;&#x2019;10% and +10%. Lennox JL, et al. Ann Intern Med. 2014;161(7):461-471.

Dolutegravir-Based Regimens in Treatment-NaÃ¯ve Patients Week 48 Outcomes

SPRING-2 Dolutegravir + FTC/TDF or ABC/3TC (n=411) Raltegravir + FTC/TDF or ABC/3TC (n=411)

Patients with <50 HIV RNA copies/mL, %

Favors Comparator

Favors Dolutegravir

88 85

2.5%

SINGLE Dolutegravir + ABC/3TC (n=414) Efavirenz/FTC/TDF (n=419)

88 81

7.4%

90 83

7.1%

FLAMINGO Dolutegravir + FTC/TDF or ABC/3TC (n=242) Darunavir/r + FTC/TDF or ABC/3TC (n=242)

ARIA Abacavir/dolutegravir/lamivudine (n=248) Atazanavir/r + FTC/TDF (n=247)

82 71

10.5% -20

-10

Adjusted Treatment Difference, % Clotet B, et al. Lancet. 2014;383(9936):2222-2231; Johnson M, et al. J Int AIDS Soc. 2016;19(suppl 7):40-41. Raffi F, et al. Lancet. 2013;381(9868):735-743; Walmsley SL, et al. N Engl J Med. 2013;369(19):1807-1818.

Elvitegravir-Based Regimens in Treatment-NaĂŻve Patients Week 48 Outcomes

Study 102 Elvitegravir/cobicistat/FTC/TDF (n=348) Efavirenz + FTC/TDF (n=352)

Patients with <50 HIV RNA copies/mL, %

Favors Comparator

Favors Elvitegravir

88 84

3.6%

Study 103 Elvitegravir/cobicistat/FTC/TDF (n=353) Atazanavir + RTV + FTC/TDF (n=355)

90 87

2.7%

92 90

2.0%

Studies 104 and 111 Elvitegravir/cobicistat/FTC/TAF (n=866) Elvitegravir/cobicistat/FTC/TDF (n=867)

WAVES Elvitegravir/cobicistat/FTC/TDF (n=289) Atazanavir/r + FTC/TDF (n=289)

87 81

6.5% -20

-10

Adjusted Treatment Difference, % DeJesus E, et al. Lancet. 2012;379(9835):2429-2438; Sax PE, et al. Lancet. 2012;379(9835):2439-2448; Sax PE, et al. Lancet. 2015;385(9987):2606-2615; Squires K, et al. Lancet HIV. 2016;3(9):e410-e420.

Bictegravir/FTC/TAF

• Noninferior to DTG/ABC/3TC with no resistance seen in either study arma • Improved tolerability profile (less nausea)b • No renal eventsc

Virologic Outcomes, % of Patients

Comparative Efficacy, Tolerability, and Toxicity 100 90 80 70 60 50 40 30 20 10 0

92.3

BIC/FTC/TAF (n=314) DTG/ABC/3TC (n=315)

Favors DTG/ABC/3TC

Favors BIC/FTC/TAF

-0.6 (-4.8, 3.6) P=0.78 1

2.5

6.7

4.4

<50 HIV-1 RNA ≥50 HIV-1 RNA No Virologic Data copies/mL copies/mL

-12

-8

-4

Treatment Difference, % Achieving HIV-1 RNA <50 copies/mL (95% CI)

BIC/FTC/TAF, a novel STR for treatment-naïve HIV-1−positive adults, has an improved tolerability profile with less toxicity. BIC, bictegravir; BMD, bone mineral density; CD4, CD4 T lymphocyte; eGFR, estimated glomerular filtration rate; STR, single-tablet regimen. N=629 patients randomized to BIC/FTC/TAF or ABC/DTG/3TC; at baseline 16% had viral load >100,000 copies/mL and 11% had CD4 <200 cells/mL. aNo resistance mutations emerged in either group; bComparing BIC/FTC/TAF to ABC/DTG/3TC, most common AEs diarrhea (13%, 13%), headache (11%, 14%), and nausea (10%, 23%); cAt W 48, mean % changes from baseline in BMD were -0.83% vs -0.60% (P=0.39; lumbar spine) and -0.78% vs -1.02% (P=0.23; total hip). No differences between treatments noted in changes from baseline for eGFR and proteinuria at W 48. Gallant J, et al. 9th International Antiviral Society Conference on HIV Science. July 23−26, 2017; Paris, France. Abstract MOAB0105LB.

ACTG A5353

Pilot Study of Dolutegravir + Lamivudine in Treatment-Naïve Patients • Phase 2 single-arm, 52-week study (n=120) – HIV RNA ≥1000 to <500,000 copies/mL; no NRTI, integrase, or PI resistance; no HBV coinfection – Age (30 years), male (87%), CD4 count (350 to 413 cells/mL), HIV RNA (4.2−5.2 log10 copies/mL)

Week 24 Virologic Outcomes Baseline HIV RNA (copies/mL)

• Primary efficacy outcome – 90% achieved HIV RNA <50 copies/mL at week 24 (FDA snapshot algorithm), regardless of baseline HIV RNA level – Virologic failure (n=3) was uncommon and associated with suboptimal adherence

>100K (n=37)

≤100K (n=83)

HIV RNA <50 copies/mL, % Virologic nonsuccess, %

• 1 virologic failure had emergent R263RK and M184V

HIV RNA >50 copies/mL • No discontinuations due to adverse events • GEMINI-1 and -2 are underway and should Other reasons provide more data on the resistance barrier to dolutegravir + lamivudine HBV, hepatitis B virus. Taiwo BO, et al. 9th International Antiviral Society Conference on HIV Science. July 23−26, 2017; Paris, France. Abstract MOAB0107LB.

ANDES Study

Darunavir/r + Lamivudine in Treatment-NaĂŻve Patients Patients With HIV-1 RNA Levels <400 copies/mL, %

24-Week Results With the 2-Drug vs 3-Drug Regimen Triple Therapy, 97%

Triple Therapy (n=68) Double Therapy (n=71)

100 80

Double Therapy, 95% Difference (95% CI): -2.5% (-7.9, 2.9)

60 40 20 0 0

Week

24 Study Ongoing

No virologic failure in 2-drug study arm and all patients with baseline HIV RNA >100,000 copies/mL in either study arm responded to therapy. Darunavir/ritonavir (DRV/r) plus lamivudine (3TC) versus DRV/r plus tenofovir/3TC. Sued O, et al. 9th International Antiviral Society Conference on HIV Science. July 23-26, 2017; Paris, France. Abstract MOAB0106LB.

IM vs Oral Maintenance Regimens

Patients With Various Virologic Outcomes, %

IM CAB+RPV LA vs Oral CAB + ABC/3TC (LATTE-2) Comparative Efficacy at 96 Weeks 100 90 80 70 60 50 40 30 20 10 0

Oral Regimen

IM CAB+RPV LA Q8W (n=115) IM CAB+RPV LA Q4W (n=115) ORAL CAB+ABC/3TC (n=56)

IM Regimen

Q8W IM 10.0 (-0.6, 20.5)

Q4W IM 3.0 (-8.4, 14.4) 13 4 HIV-1 RNA <50 copies/mL

No Virologic Data HIV-1 RNA ≥50 copies/mL

-12

-9

-6

-3

Treatment Difference, % Achieving HIV-1 RNA <50 copies/mL (95% CI)

The LA 2-drug regimen injected IM either Q8W or Q4W resulted in higher virologic response rates and was well tolerated. CAB, cabotegravir; IM, intramuscular; LA, long-acting; Q4W, every 4 weeks; Q8W, every 8 weeks; RPV, rilpivirine. Randomized, open-label, phase 4 study. Eron J, et al. 9th International Antiviral Society Conference on HIV Science. July 23−26, 2017; Paris, France. Abstract MOAX0205LB.

Switching to Dolutegravir + Rilpivirine

Pooled Outcomes From SWORD 1 and SWORD 2 Efficacy at 48 Weeks Patients With <50 HIV-1 RNA copies/mL, %

• DLT + RPV was noninferior to standard ARTa • No integrase-inhibitor treatment-emergent resistance in either study arm

100 90 80 70 60 50 40 30 20 10 0

DLT + RPV (n=513)

Standard ART (n=511)

DLT + RPV is a promising option when switching to a 2-drug regimen aStandard ART,

prior ART regimen that resulted in undetectable viral load. Llibre JM, et al. 24th Conference on Retroviruses and Opportunistic Infections; February 13−16, 2017; Seattle, WA. Abstract 44LB.

Regimen Simplification

Darunavir + 3TC vs Darunavir + TDF/3TC (ANDES) Patients With HIV-1 RNA Levels <400 copies/mL, %

24-Week Results With the 2-Drug vs 3-Drug Regimen Triple Therapy, 97%

Triple Therapy (n=68) Double Therapy (n=71)

100 80

Double Therapy, 95% Difference (95% CI): -2.5% (-7.9, 2.9)

60 40 20 0 0

Week

24 Study Ongoing

ACTG A5257 Study

Genotypic Analysis for Resistance at Virologic Failure • Virologic failure with resistance Virologic Failure, Numbers at Week 96 ATV/r RAL DRV/r was rare but more frequent in (n=95) (n=85) (n=115) the raltegravir arm Genotypic testing 75 65 99 Resistance • 3.0% in raltegravir arm • Any 9 18 4 – 2 patients developed intermediate-level resistance to dolutegravir

• <1.5% in boosted PI arms – Integrase inhibitor–resistance in 2 patients could not be explained All patients received emtricitabine/TDF. Lennox JL, et al. Ann Intern Med. 2014;161(7):461-471.

• PI

• Overall

• Emtricitabine

• Tenofovir DF

• Emtricitabine and TDF

Integrase inhibitor-only NRTI and integrase inhibitor

• Overall

• Emtricitabine and raltegravir

• Emtricitabine, TDF, and raltegravir

NRTI-only

No One Right Option for Everyone Limitations of Current First-line Regimens

• Elvitegravir/cobicistat

• Raltegravir-based regimens

– Low barrier to resistance

– Twice-daily administration

– Drug-drug interactions

– Relatively low barrier to resistance

• Dolutegravir – Only available with abacavir/lamivudine (limited to HLA-B*5701−negative patients)

– Not available as a single-tablet regimen

• Ritonavir-boosted darunavir regimens – Higher pill count – Drug-drug interactions – Gastrointestinal toxicity – Not available as a single-tablet regimen

EXPEDITION-2: Glecaprevir/Pibrentasvir Treating HCV in Patients Coinfected With HIV-1

Patients With SVR12, %

Efficacy at 8 Weeks 100 98

80 60 40 20

150 153

150 151

ITT

mITT

• On-treatment virologic failure detected at week 8 in 1 patient with GT3 infection and cirrhosis – Patient was <85% adherent to treatment regimen – Evaluation at posttreatment week 24 showed that the patient achieved SVR

Will shorter courses of HCV therapy matter to payers and patients? GT3, genotype 3; ITT, intention to treat; mITT, modified intention to treat; SVR, sustained virologic response; SVR12, sustained virologic response for ≥12 weeks following the end of therapy. Rockstroh J, et al. 9th International Antiviral Society Conference on HIV Science. July 23−26, 2017; Paris, France. Abstract MOAB0303.

Two Emerging Trends in ART and HCV Treatment

Moving from 3-drug to 2-drug ART regimens

Shorter treatment courses for HCV in patients with HIV coinfection

Targeting High-Risk MSM Subgroups With HIV PrEP PrEP NNT to Prevent 1 HIV Infectiona

70 60

70 49.4

NNT Incidence Reduction Prevalence Reduction

50 40

30 20 10

14.7 10.4 3.9

10 13.1

13.9

2.9

3.9

9.4 3.1

Reduction in HIV Incidence or Prevalence, %b

Model’s Estimated Effects of PrEP as a Prevention Strategy Shows Overall Lower NNT and Higher Public Health Benefit Statin NNT to prevent 1 myocardial infarction=56

0 MSM BMSM YBMSM HMSM YHMSM CDC, Centers for Disease Control and Prevention; MSM (B, black, YB, young black; H, Hispanic; YH, young Hispanic); NNT, number needed to treat. aPrEP offered to all MSM at high risk for HIV infection (HIV Incidence Risk Index for MSM >10); bAgent-based microsimulation model calibrated to represent HIV prevalence by race among MSM in US (2010−2013; data from CDC). Elion R, et al. 9th International Antiviral Society Conference on HIV Science. July 23−26, 2017; Paris, France. Abstract 1579.

Clinical Data Needs and Resources How Does the Clinician Use the Data?

• Most current clinical research data – Efficacy, safety, and other clinical outcomes with ART regimens – Regimen adherence

• Most current nonclinical data – Access and affordability – Payer-specific ART options

• Considerations when using clinical data – Select data types that are useful when developing practice patterns – Use data types and forms that can be easily communicated to payers and facilitate synthesis of clinical benefits and pharmacoeconomic evaluations

THE MEDICAL-DIRECTOR PERSPECTIVE Robert LoNigro, MD, MS

ART Adherence Is Now Key to Optimizing Viral Suppression • AIDS Case management • HIV disease Medication adherence • Good adherence to currently recommended ART regimens can virtually eradicate the viral load • Disorders associated with immunocompromise are now rare – Pneumocystis carinii pneumonia (ie, P jiroveci) – Cryptococcosis – Kaposi sarcoma – Exceptions usually caused by poor adherence and/or treatment resistance

A New Focus for HIV Care Management • Payers and providers no longer primarily focus on HIV-related medical complications • Increasingly devoted to maximizing medication adherence –Prevents treatment resistance –Reduces treatment failure –Inhibits reemergence of an immunocompromised state

Formulary Management Strategies Out With the Old and In With the New

• Traditional formulary management generally fails to optimize clinical and cost-related outcomes in HIV management • Limiting access to effective drugs can prevent clinicians from Formulary individualizing ART regimens management based on psychosocial factors • Newer formulary management strategies address psychosocial determinants of successful outcomes

Clinical and cost-related outcomes

Psychosocial Determinants of Successful Treatment Outcomes

Cost-control measures

Potential Barriers to ART Adherence • Side effects • Dosage frequency • Ability to obtain follow-up care • Financial and transportation needs • Housing concerns • Comorbid conditions

Psychosocial Determinants as the Primary Cause of Treatment Failure â&#x20AC;˘ Drug resistance develops when the medication is taken intermittently â&#x20AC;˘ Unrecognized drug resistance leads to treatment failure and immunocompromise â&#x20AC;˘ A collaborative approach between payers and providers can prevent these treatment outcomes

Drug Cost Is a Small Piece of the Puzzle Effective HIV treatment can virtually eliminate opportunistic disease

Preprescribing laboratory testing can help determine the preferred treatment regimen

Cost

Cost burdens of immunocompromised states far exceed the overall cost of ART regimens

Expertise in Current HIV Management Informs Formulary Decisions • Improve access and treatment adherence – Avoid step therapy – Cover brand-name drugs – Limit effects of older formulary management strategies

• The complexities of available prescribing options require expertise in HIV care • Pharmacy programs should communicate with local and national experts regularly

A Collaborative Approach to Treatment Decision Making • The decision-making team – Prescriber – Patient – Pharmacist – Case manager – Family/social support services

• Identify barriers to effective care….We ALL have them • Develop a treatment plan to mitigate poor adherence • Ensure all members of the treatment team understand the plan • Monitor, monitor, monitor!

Barriers to the 3 A’s of ART

• Access barriers

• Affordability barriers

– Transportation – Formulary design – Provider follow-through – Psychosocial support – Personal/family resources – Community supports – Benefit design • Copay • Cost sharing

IQ, intelligence quotient.

• Adherence barriers – Treatment-team relationships – Functional/intellectual capacity – Health IQ – Influence of social media – Comorbid behavioral issues, including substance abuse – Comorbid medical conditions – Adverse effects of therapy

Individualized HIV Treatment Is Key • Medication therapy for HIV disease no longer fits clinical and cost paradigms from older managed-care strategies • Effective care teams consider all possible barriers and develop treatment plans that minimize poor adherence and treatment failures • HIV is an eradicable disease when effective treatment is delivered and received

HOW AND WHERE DO THESE PERSPECTIVES AND CONSIDERATIONS INTERSECT? James A. Jorgenson, RPh, MS, FASHP

Trends in Overall Drug Costs • US prescription-drug expenditures topped $450B in 20151 • Drugs represent 16.7% of total US healthcare expenditures1 • By 2018, drug costs in the US could hit $535B1 • 2013 saw the most newly available molecular entities in the last 10 years2 – Innovative new products serving unmet medical needs or otherwise advancing patient care and public health

1. The Alliance for Health Policy Web site. The Sourcebook: Essentials of Health Policy. Chapter 5: Health Care Costs. 2017. www.allhealthpolicy.org/sourcebook/health-care-costs/. Accessed October 4, 2017; 2. US Food and Drug Administration. Approved Drugs 2013. www.fda.gov/downloads/drugs/developmentapprovalprocess/druginnovation/ucm381803.pdf. Accessed October 4, 2017.

HIV Medications • Options1 – Nucleoside reverse transcriptase inhibitors (NRTIs) – Nonnucleoside reverse transcriptase inhibitors (NNRTIs) – Nucleotide reverse transcriptase inhibitors (NtRTIs) – Protease inhibitors – Entry inhibitors, including fusion inhibitors – Integrase inhibitors – Combinations of medications from different classes

• Costs2,3 – Average monthly cost: $2,000−$5,000 – Average lifetime cost: $500,000 1. DHHS. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2016. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed October 5, 2017; 2. CDC. HIV Cost-effectiveness. Updated March 2017. www.cdc.gov/hiv/programresources/guidance/costeffectiveness/index.html. Accessed October 5, 2017; 3. Nakagawa R, et al. PLoS ONE. 2015;10(4):e0125018.

Payer Actions

Addressing Rising Costs With Cost-Control Measures • Narrowed networks • Out-of-pocket costs • Formularies/preferred-drug lists • Specialty tiers • Step therapy or fail-first paradigms • Prior authorization • Exclusion of recently launched drugs • Rejection of third-party premium assistance • Increased premiums

Pharmacoeconomic Evaluations â&#x20AC;˘ Evaluate the cost and value of a drug considered for formulary admission â&#x20AC;˘ Compare the drug to available alternative therapies based on efficacy, safety, and cost â&#x20AC;˘ Assess costs and clinical, economic, and humanistic outcomes for different therapies within the same drug class or across classes

Drug Under Consideration

Available Alternative Therapies

Is the Therapy Good Value for the Cost?

More Effective More Expensive

Less Effective Less Expensive

More Effective Less Expensive

Costs

Less Effective More Expensive

Effectiveness

Calculating Drug Costs â&#x20AC;˘ A drugâ&#x20AC;&#x2122;s calculated value should include not only the price of the medication, but also costs related to the entire treatment approach Direct medical costs

Indirect costs

Direct nonmedical costs

Intangible costs

Integrating Multiple Perspectives • Different perspectives on these analyses should be considered – Society – Provider – Patient – Payer

• Most managed-care formulary decisions focus primarily on direct medical costs

BOTTOM LINE: Is the therapy a good value for the cost?

Types of Pharmacoeconomic Evaluations • Cost-identification/cost-minimization –Estimates costs, but not benefits, of an intervention –Appropriate when 2 equally effective therapies are compared –Comparisons of generic drugs to trade-name equivalents

• Cost-effectiveness analysis –Estimates costs as well as outcomes that may not be equivalent or monetizable –Expressed as a ratio with measurable gain in health as the denominator

Types of Pharmacoeconomic Evaluations (Cont’d)

• Cost-utility evaluation –Special type of cost-effectiveness analysis –Costs are valued in monetary units and outcomes are valued in quality-adjusted life years

• Cost-benefit evaluation –Costs and outcomes are valued as monetary units –Adjusted for the time value of money –Expressed as net present values

AMCP Dossier

A Format for Submission of Clinical and Economic Evidence of Pharmaceuticals in Support of Formulary Consideration • Intended to improve timeliness, scope, quality, and relevance of information • Streamlines evidence gathering and review process • Supports formulary decisions – Standardizes communication about product information – Requires projections of product’s benefits and risks – Provides information on product value – Makes evidence more clear, transparent, and evaluable for decision-makers AMCP, American Managed Care Pharmacy. AMCP Format for Formulary Decisions. Version 3.1. AMCP. 2012. http://www.amcp.org/practice-resources/amcp-format-formulary-submisions.pdf. Accessed September 28, 2017.