Agenda: Opportunities in Developing Orphan Drug Products. Mukesh Kumar, PhD, RAC

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1 This Seminar is Brought to you by Amarex Clinical Research Washington DC metro area A Product Development Services Company From Lab to Market Approval FDA Meetings Global Regulatory Submissions Global Clinical Trials Statistics & Data management Strategy Implementation Pre-Clinical Assays Opportunities in Developing Orphan Drug Products Mukesh Kumar, PhD, RAC Senior Director, Regulatory Affairs Amarex Clinical Research Germantown, MD Contact: Patrick Burke at patrickb@amarexcro.com Nov 2009 Agenda: Definition of Orphan Products Designation of status Incentives available Facts and Myths Strategic considerations for development What is an Orphan Drug? A drug (or biologic) intended to treat a rare disease or condition affecting fewer than 200,000 persons in the United States or A drug (or biologic) which will not be profitable within 7 years following approval by the U.S. Food & Drug Administration. 3 What are Orphan Diseases? Affects <200,000 persons in the US Affects >200,000 in US, no expectation that therapeutic development costs will be recovered from sales in the US Includes over 6,000 rare diseases Collectively affects approximately 25 million Americans Frequently serious/life threatening The U.S. Orphan Drug Act (ODA) Signed in 1983 US Congress established the public policy that the Federal Government could/would assist in the development of products for the diagnosis, prevention or treatment of rare diseases or conditions. Established Office of Orphan Product Development (OOPD) within the FDA 1

2 The Mission of OOPD To assist and encourage the identification, development, and availability of safe and effective products (drugs, biologics, devices and medical foods) for people with rare diseases/disorders by offering: Incentives Fee waivers Grants Assistance The First Step: DESIGNATION of ORPHAN STATUS What Drugs Can Be Designated? Eligibility: New Drug New orphan indication for an approved drug 505(b)(2) drug (generic drugs are not eligible) Designation request submitted prior to filing a New Drug Application (NDA) DESIGNATION vs. APPROVAL DESIGNATION = A product obtains an ORPHAN STATUS for the particular indication and becomes eligible for the available incentives. APPROVAL = Product receives US marketing approval for one or more specific indication. OOPD is not involved in approval decision What are the Incentives for Orphan-Drug Designation? 7-year marketing exclusivity to the first sponsor obtaining FDA approval of a designated drug Tax credit equal to 50% of clinical investigation expenses Exemption/Waiver of application (filing) fees (PDUFA) Assistance from OOPD during the development process May be helpful for obtaining Orphan Grants Marketing Exclusivity Company receives 7 years of marketing exclusivity upon FDA approval of a specific orphan drug for a specific indication. How does this help the developer? FDA cannot approve the same drug for the same indication during the exclusivity period 2

3 Tax Credits for Orphan Designated Products A 50% tax credit for clinical research and testing expenses How does this help the developer? The credit can be applied to Federal taxes incurred in the prior year and for up to 20 years against future taxes NDA Review Fee for Orphan Designated Products Congress exempted designated orphan products from the user fee requirement How does this help the developer? A developer saved the user-fee of $1,247,200 per application, which would otherwise be paid to FDA at the time of submission of NDA. How to obtain a Designation? Sponsor submits a designation request to FDA/OOPD OOPD Staff review requests. Criteria includes: Is population < 200,000 in the U.S. (prevalence)? Is there rationale for the use of the drug in the proposed indication/disease condition? How to obtain a Designation? Definition of rare disease credible literature or database National Organization of Rare Diseases (NORD) OOPD s earlier findings WHO, UN reports of disease incidence Dissection of an indication Sub-set of a larger indication to define a smaller population Occurrence rate in the US per year Personalized medicine not yet defined And then what? Once designated the OOPD may act as a liaison with the sponsor and the review division in the development of the product OOPD does not review the product for safety or efficacy OOPD does not approve the product for marketing New Joint Template Form for US and EMEA Established 11/2007 Can be submitted for designation to US and EMEA Form FDA 3671 ( _508.pdf) 3

4 Orphan Drug Designation Increases Probability of Success Reduced clinical and non-clinical testing requirements Faster review by the FDA (via a separate Fast-Track Designation) Small application size, i.e., low cost Fee waivers NDA amendment later to include other indications Orphan Drug Designation Increases Probability of Success 2/3 Designation requests are successful More than 330 orphan-designated products have received FDA approval for marketing. Total market size for Orphan drugs is about 25 million patients in the US alone In Billions, combined An individual drug could be quite profitable Humanitarian Use Device (HUD) Designation What are HUDs? A HUD is a medical device intended to treat or diagnose a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year (incidence): id Designation by OOPD A HUD then undergoes further FDA/CDRH review to determine if it qualifies for a Humanitarian Device Exemption (HDE). FDA/CDRH approval of a HDE authorizes marketing of the HUD. Why Humanitarian Device Exemptions? Premarket approval applications for new medical devices ordinarily must show that products are safe and effective. For very rare diseases, FDA will approve such devices if manufacturers demonstrate the safety and probable benefit to patients. HDE provision is the exemption from the effectiveness standard. Contacts Request for HUD Designation goes to Office of Orphan Products Development: HDE application goes to CDRH/ODE: e/1381.pdf 4

5 Orphan Products Grants Program OOPD Grants Program Goal of the Grants Program: to encourage clinical development of products, including drugs, biologics, medical devices, or medical foods, for use in rare diseases or conditions (affecting <200,000 individuals) in the U.S. Also a practical program for advancing marketing approvals and relevant publications that impact care for rare diseases Orphan Products Grants Program Application, review, and scoring much like NIH grant application Request for Application (RFA) available at Electronic submissions: Orphan Products Grants Program Approximately 80 applications per year from Domestic or foreign, public or private, for-profit or nonprofit entities Competitive grant program Fund about new grants per year Supports academic and industry sponsored research Orphan designation is not a grant requirement Grants Program: Requirements Clinical studies to be conducted under: Active IND or IDE Good Clinical i l Practices (GCP) Human Subjects Assurance from OHRP Federal-Wide Assurance or FWA ( IRB approval Grants Program: Budget The current annual budget for grant funding is approximately $14 million Clinical trials may be awarded (in total costs (direct and indirect)): Up to $200,000 (Phase 1) per year for up to 3 years Or Up to $400,000 (Phase 2 and 3) per year for up to 4 years 5

6 Grants Program: Review Process Primary Review: Grants scored by independent ad hoc expert panels for technical merit Criteria are in the RFA Funding based on scores ( lower scores are better) The recent fundable range was Summary Statements contain review specifics Second Level review by a National Council (process approval) OPD Project Officer checks prefunding certifications prior to funding (check IRB, foreign sites, etc.) Other Incentives OOPD assistance in drug development process Protocol Assistance Liaison with FDA Reviewing Divisions Working with the public-interest and advocacy groups to identify concerns and resources. Informing academia and industry of the incentives and opportunities for developing products for use in rare diseases or conditions. Challenges For the Development of a Drug for a Rare Disease The development of a drug product to treat a rare disease same as for a common disease 2 well controlled clinical i l trials (preferred) Must meet the FDA statutory standards for safety and effectiveness. Myths Orphan drugs have limited profit Nich markets Low competition Longer exclusivity Loyal customers Once Orphan always Orphan NDA amendments to add non-orphan indications Multiple Orphan designations for the same product Pricing and Insurance control by regulators No price control in the US Insurance companies cannot deny FDA-approved treatments 34 Strategic Planning for Orphan Products First target indication for a new product Block-buster Vs Orphan Request for Designation Discussions with the FDA Pre-IND meeting(s) Protocol assistance Liaison requests First NDA approval Subsequent NDA amendments Thank You! Mukesh Kumar, Ph.D. Sr. Director, Regulatory Affairs and Quality Assurance Amarex Clinical Research Century Boulevard, Suite 450 Germantown, MD Tel: (240) Fax: (301) mukeshk@amarexcro.com