Novel Treatments for Orphan Diseases: a Promising Future September 20Th, 2019

Novel Treatments for Orphan Diseases: A Promising Future September 20th, 2019

Lauren Megargell, Pharm.D. Director, Clinical Services

Amanda Williams, Pharm.D. Pharmacist, Clinical Market Intelligence Learning Objectives

• Define the Food and Drug Administration (FDA) orphan designation

• Identify orphan drugs recently approved and in the near-term pipeline

• Describe disease prevalence and alternative treatment options

• The presenters for this activity has been required to disclose all relationships with any proprietary entity producing health care goods or services, with the exemption of non-profit or government organizations and non-health care related companies.

• Lauren Megargell, Pharm.D. – PerformRx Employee • Amanda Williams, Pharm.D. – PerformRx Employee – ApotheCare Services, Managing Partner

Which of the following drugs is used to treat an orphan disease?

A. Botox® (onabotulinumtoxinA) B. Humira® (adalimumab) C. Zolgensma® (onasemnogene abeparvovec-xioi) D. All of the above

An orphan disease affects less than ______people in the United States.

A. 50,000 B. 100,000 C. 200,000 D. 500,000

Which of the following is disease – drug pairings is not correct?

A. Tuberculosis – Avapritinib B. Duchenne Muscular Dystrophy – Golodirsen C. Erythropoietic Protoporphyria – Afamelanotide D. Atypical Hemolytic Uremic Syndrome – Ravulizumab- cwvz

• Orphan Drug Act of 1983 • Drug to treat or prevent a rare disease (e.g. affecting < 200,000 people in the United States) OR that affects > 200,000 people but is not expected to recover development and marketing costs • Designation is specific to a unique drug/disease combination • “Orphan” subset – a drug for only a subset of persons with a particular disease or condition that otherwise affects 200,000 or more people

• Approximately 7,000 orphan diseases affecting 25-30 million people in the U.S. • More than half of those afflicted are children • Treatments are available for ~5% of the estimated 7,000 diseases • 80% are genetic in nature • 7.9% of drug spending in the United States is attributed to orphan indications – 20% of drugs are priced at less than $6,000/year – 1% of drugs are priced in excess of $500,000/year

IQVIA National Sales Perspectives, Jun 2017; FDA Orphan Drugs Database, Feb 2017; IQVIA Institute, Aug 2017

• Financial incentives – development costs for orphan drugs are LOWER than non-orphan – Tax credits for clinical testing – Research and development grants for clinical trials – Waive User Fee associated with the application (currently $2.5M) • Extended market exclusivity – New drug – 5 years – Orphan drug – 7 years – Biologic – 12 years

• Development process – IND, Phase I-III, NDA/BLA • Office of Orphan Products Development (OOPD) • Expedited review pathways – Priority Review – from standard 10 month review to 6 month review – Accelerated Approval – approval based on surrogate endpoint – Breakthrough – for drugs that demonstrate a substantial improvement compared to currently available therapies – Fast Track – for drugs to treat serious conditions and fill unmet medical needs

• Difficulty in identifying and enrolling patients • Multiple sites, including international • Defining and measuring outcomes • Limited sample size means treatment effect needs to be high to achieve power

Development Timeframes

Ultra-orphan drugs

Orphan drugs

All new drugs

0 2 4 6 8 10 12 14 16 18 20 Years

Orphan Drug Approvals by Year 100

40 Designation Approvals Number of Drug/ Unique 30

0 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Year

Market share sales growth 2019 - 2024 ─ Orphan drugs: +25% ─ Brand drugs: -4.3% ─ Generic drugs: -9.7% Worldwide Sales Forecast 1400

1200

1000

800

Sales ($bn) 600

400

200

0 2019 2020 2021 2022 2023 2024 Year

Orphan Generic Brand

Drug Approval Date Manufacturer Indication Pricing Acquired CabliviTM Thrombotic $277,400/ (caplacizumab 02/06/2019 Sanofi Thrombocytopenic course -yhdp) Purpura (aTTP)

• Unique Designator: Fast Track • IV, SQ Inhibits the interaction between von Willebrand factor (vWF) and platelets, thereby reducing both vWF-mediated platelet adhesion and platelet consumption • First agent to carry a labeled indication for aTTP • Prevalence is estimated at 3 cases per 1 million adults per year