Join the 13th Annual EveryLife Foundation Rare Disease Scientific Workshop on October 20th

Workshop Goals:

1. Identify the research, regulatory and access policy barriers to increasing the utilization of the Accelerated Approval pathway for rare disease therapeutic development by examining a series of real-world case studies.
2. Generate a 1, 3- and 5-year action plan for how the Accelerated Approval pathway can be optimized to meet the critical need for new rare disease therapies.

The Workshop will address topics such as:

1. When is a biomarker the only path forward for drug development (for example: the disease progression is very slow, ethical issues, etc.)?
2. Can we use primary biomarkers that reflect the underlying cause of disease to advance drug development in rare diseases?
3. When is a biomarker a better measure of a treatment’s efficacy?
4. Experiences with roadblocks to using the Accelerated Approval pathway (for example: qualification process, accessing the pathway, access environment, etc.).
5. The design, startup and execution of confirmatory studies.
6. Ensuring timely patient access to Accelerated Approval treatments (for example, early communication with payers, alternative/outcomes-based payment models, etc.).

Background:

The Accelerated Approval Pathway, one of FDA’s expedited pathways, was established over 25 years ago and codified in the 2012 FDA Safety and Innovation Act (FDASIA), part of PDUFA V. Accelerated Approval allows for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint, a marker, such as a laboratory measurement, that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Sponsors are required to conduct post-approval (phase 4) confirmatory studies to confirm clinical efficacy. If successful, traditional approval is then granted, however drugs can be removed if confirmatory studies fail to show clinical benefit.

In the 2012 FDASIA, language was included to increase the use of Accelerated Approval, directing that the FDA to consider “any unique issues associated with very rare diseases” and that the FDA “shall consider how to incorporate novel approaches into the review of surrogate endpoints involved in the pathophysiologic and pharmacologic evidence in such guidance, especially in instances where the low prevalence of a disease renders the existence or collection of other types of data unlikely or impractical.”

In the years since FDASIA the resulting guidance documents have failed to spur greater use of Accelerated Approval for rare diseases and (insert data point on number of rare approvals using AA compared to overall). While the pathway has had recent success in facilitating novel therapies to the market in oncology, barriers to wider adoption in rare disease remain. These barriers include upstream regulatory concerns such as lack of appropriate guidance to qualify surrogate endpoints in small populations and clinical trial design and conduct issues for the required confirmatory. More recently, downstream access concerns have emerged that could be chilling the appetite for investing in Accelerated Approval programs and leaving patients without access to a beneficial treatment.

Among the public, payers and policy makers there is a generalized misunderstanding of the Accelerated Approval pathway and the level of evidentiary requirements that approved treatments attained. Public concern has been voiced about the timing and pace of confirmatory studies and these concerns, along with questions about the overall efficacy of drugs approved via the pathway, have led to suggestions that payers treat Accelerated Approval drugs differently until confirmatory studies are done. If implemented, many of the recommendations put forth by MACPAC, ICER and others would compound an already complex access environment faced by patients and would likely contribute to lost opportunities for the 95% of rare diseases that still have no approved treatments.

The growing frustration with the regulatory factors leading to underutilization of the pathway for rare diseases and the evolving access threats were compounded by the very public conversation around the FDA’s decision to leverage the pathway to approve a novel treatment for Alzheimer’s disease in June. With science and novel technology offering unprecedented opportunities to tackle the 95% of rare diseases with no approved treatments, it is incumbent on the rare disease community to come together and identify solutions that will lead to the optimization of the Accelerated Approval pathway for the approval of and access to novel rare disease treatments.