CURE THE PROCESS 2:Improving the Development Process

for Rare Disease Treatments

Emil D. Kakkis, M.D., Ph.D.President and Founder

October 29, 2014

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About the Foundation:• Dedicated to Accelerating Biotechnology

Innovation for Rare Disease Treatments• Advocating practical and scientifically sound

change in policy and law to increase the predictability of the regulatory process through scientific analysis and dialogue, grassroots support & expert-led workshops.

• Foundation Mission:– No disease is too rare to deserve treatment– All treatments should be safe & effective– We could be doing more with the science we

already have2

Roadblocks in the Development of Rare Disease Treatments• More challenges for rare diseases than common diseases

– Due to their rarity, there is often limited understanding of the clinical disease, even if the science underlying the disease is clear

• Lack of a defined regulatory pathway based on: – Limited prior clinical study experience and no natural history

information – Challenges defining new clinical endpoints to assess efficacy– Lack of acceptable biomarkers indicating clinical improvement– Fewer variable patients to participate in clinical trials, thus

requiring alternative clinical trial designs and analysis.

• Potential treatment development cost requirements are too great and too uncertain for many rare diseases, making them less attractive to investors

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• Launched May, 2009 at the Rare Disease Summit in Washington, DC

• Tasked with improving the clinical development and regulatory process for rare diseases through science-driven changes in public policy

First Cure The Process Campaign

Original Goals of theCURETHEPROCESS Campaign• Specialize Review: Establish a new Office of

Drug Evaluation specifically for Biochemical and Genetic Diseases

• Increase Accelerated Approvals :Create new qualification criteria for surrogate endpoints to allow Subpart H Accelerated Approvals

• Improve Clinical Designs and Analyses: Devise acceptable optimal statistical analyses and alternative designs for clinical endpoint driven pivotal studies

Moving a Vision to Reality• Goal: Science-driven public policy changes • Initiated Workshop Series

– Science-based discussion– Rational strategies– Development solutions– Drive policy ideas

• Organized & educated patient groups– A unified force to compel change

• Published White Papers • Worked with Congress to move Legislation

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Success in Moving Legislation Through Congress: ULTRA/FASTNew law expands access to Accelerated Approval process

• Drafted legislation with Reps. Stearns & Towns –ULTRA/FAST Acts

• Vigilant communication and cooperation with key stakeholders

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• FAST language inside the PDUFA V bill (FDASIA, S. 3187)• Organized the patient community as a political force

• 300+ patient organizations signed on to support ULTRA/FAST• 3,675 emails were sent to Congress to support ULTRA/FAST

FDASIA signed by President Obama July 9, 2012• Working with Stakeholders to Implement Legislation

Thank You to Our 181 Partners

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FDASIA is a Great Start but More Needs to be Done

• Lack of expertise and specialization on complex rare diseases in drug review divisions

• Early stage clinical trials start first oversees, delaying access to treatments for US patients

• Companies are not repurposing drugs for rare diseases, forcing patients to use off label drugs with no safety or efficacy data

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Introducing Cure The Process 2

• Rationalize: Encourage the FDA to accommodate a more scientifically rational and flexible application of safety data to allow US patients to have access to early stage clinical trials.

• Incentivize: Enact legislation encouraging industry to repurpose major market drugs for rare disease patents or “rare-purpose” drugs to ensure patients have access to safe, effective and affordable treatments.

• Specialize: Encourage the FDA to create more specialized drug review divisions and allow reviewers access to the latest science to facilitate a better understanding of the diseases they are reviewing.

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Specialization for Review Decisions on Rare Diseases

• Specialized experience and training• Allowing for concurrent academic activities will let

reviewers keep informed on the latest science• Allow sufficient therapeutic focus to be an expert• Allow sufficient time to research complex target

indications and to hone skills

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The needs of the increasingly complex rare disease therapeutic areas are

creating additional challenges for FDA

No Disease Is Too Rare to Deserve Treatment 12

Rationalizing Safety Requirements• The FDA’s requirements are causing early stage clinical trials

to be moved outside the US• US patients are being denied access to these potentially

lifesaving trials• To avoid delays, many rare disease programs have left

the US• FDA should follow the same ICH guidelines and risk-based

flexibility that are applied by other competent authorities• Rationalizing treatment safety:

• Refine current toxicology requirements to a model using better risk-based scientific justification

• Most importantly, always ensure treatments are safe & effective

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Rare Disease Scientific Workshop

• Hosted Scientific Workshop in 2014 on “Rationalizing Safety Testing to Enable Clinical Studies and Approval in the US for Rare Disease Treatments”• Developing paper based on Workshop outcomes

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Incentivize the Investment inRare Disease Drug DevelopmentIntroducing Orphan Product Extensions Now Accelerating Cures & Treatments (OPEN ACT) before Congress in November

• Hundreds of large market patented drugs exist with novel technologies and diverse possible uses

• Companies will not invest to test these drugs in rare diseases– No financial incentive– Increased risk that adverse events might taint the

product when treating very sick orphan diseases

• Can we create an incentive to study patented drugs in rare diseases as soon as they are approved?

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How a New Orphan Product Repurposing Exclusivity Could Work:Qualifying for OPEN-Act Extensions• Sponsor receives FDA approval for their major market

drug or has a current approved drug still under patent protection

• Sponsor could seek rare disease indications to extend its patent life & protect revenue from market competition for 6 months• Must be a Rare Disease – under 200,000 patients in

the US• Must qualify for Fast Track Designation: serious or

life-threatening disease• Must obtain data to place the new rare disease

indication on the label 16

How a New Orphan Product Repurposing Exclusivity Could Work:The Development Process

• Sponsor begins rare disease indication development:• multiple trials for multiple rare diseases• Establish the dose, the safety and the efficacy• High quality rigorous studies conducted

• Company receives new rare disease indication on the label• Safety, efficacy and dosing demonstrated

• Obtains 6 months additional market exclusivity at the end of the product’s patent life or NCE exclusivity period• Would stack on top of BPCA to provide an additional

incentive to develop pediatric cancer & rare pediatric disease treatments 17

Key Benefits of Rare-Purposing*in the OPEN-ACT to Speed Development• Sponsor already exists for the program • Leverages existing expertise of clinical development

staff and scientists• Manufacturing and toxicology work complete• Safety is known in humans• Reduced time for development trials & approval

• Focus on science, and rare disease clinical studies • Rare-purposed Orphan Drugs will likely cost less than

typical orphan products: Drug price will be set by the large market indication; less than typical orphan drugs

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Outcomes – Win Win WinPatients, Companies, Economy

• Public Health: Patients have access to safe & effective treatments more quickly

• Reduced Drug Prices: Repurposed drugs will be priced at major-market rates

• FDA: Improved academic excellence, increased specialization, and the best science will ensure the US maintains the best regulatory standards

• Economy: Increased biotech investment, renewed innovation and more high quality US jobs in biotechnology

21st Century Cures Initiative

• Implementation of the Cure The Process 2 goals has already begun with the 21st Century Cures Initiative• Submitted White Paper comments on first series of

21st Century Cures Roundtables• PDF of comments available on EveryLife Foundation Website

• Working closely with Energy & Commerce Committee Leadership

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Help Us Reach Our Goal of 200 Partner Organizations

• Endorsement packet included in webinar confirmation email, or visit www.CureTheProcess.org to download

• Review the provided materials, and have the endorsement letter signed by the organization’s most-senior executive

• Submit your endorsement letter to CureTheProcess@everylifefoundation.org

• Promote the campaign to your members & partner organizations 21

How to get involved:

Questions?

Be Sure to Follow us • www.CureTheProcess.org• @CureTheProcess on Twitter

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