At Long Last, FDA Unveils Plan for Rare Disease Innovation Hub

On July 17, 2024, FDA announced the establishment of a Rare Disease Innovation Hub (the “Hub”) to enhance and improve outcomes for patients with rare diseases and conditions by focusing on rare disease drug and biological product development across the Agency’s Center for Drug Evaluation and Research (“CDER”) and Center for Biologics Evaluation and Research (“CBER”). Importantly, the Hub is intended to establish a new model within FDA, which leverages cross-Agency expertise in providing guidance and conducting reviews for products for rare disease populations. First announced by Dr. Peter Marks at James Valentine’s FDA Rare Disease Town Hall session at the DIA Annual Meeting last month (see Pink Sheet coverage here), this Hub is intended to serve as the Center of Excellence that we in the rare disease community have been calling for its establishment over the last several years.

The creation of the Hub comes on the heels of relentless advocacy by the rare disease community for a Rare Disease Center of Excellence that was first proposed by Hyman, Phelps & McNamara’s own Frank Sasinowski and James Valentine nearly 6 years ago (see the initial call to action here). We commend FDA for implementing this vision (yes, even if called a Hub rather than a Center of Excellence) as it is critical that lessons learned and best practices be implemented more consistently across the Agency as we now have significant experience in the science of small trials and innovative approaches to establishing the safety and effectiveness of orphan drugs.

We also commend and congratulate the legions of rare disease patient advocates and the leadership of the EveryLife Foundation for Rare Diseases (“ELF”) who championed the advocacy efforts that led to this important milestone.

Early Direction for the Rare Disease Innovation Hub

The Hub, which will be co-chaired by Drs. Peter Marks and Patrizia Cavazzoni, spans across both Centers, and will collaborate with the Center for Devices and Radiological Health, Oncology Center of Excellence, Office of Orphan Products Development, and Office of Combination Products.  Thus far, FDA has announced three primary functions for the Hub:

1. Serve as a single point of contact for engagement with rare disease community stakeholders, including patient advocacy organizations, trade organizations, and academia;
2. Enhance inter-Center collaboration on scientific, clinical, and policy issues related to rare disease product development, including approaches related to product review, and promote consistency across Centers and offices; and
3. Advance regulatory science with dedicated workstreams on key opportunities to advance rare disease product development, such as clinical outcome assessments, biomarkers, innovative trial designs, real world evidence, and statistical approaches.

FDA also announced the creation of a new senior leadership position within the Hub, the Director of Strategic Coalitions, who will also serve as the Associate Director of Rare Disease Strategy in CDER, similar to how many Oncology Center of Excellence leadership held positions both within the Center of Excellence but also within the medical product centers.  This individual will play a key role in overseeing the new integrated Hub model and helping to develop and implement its strategic agenda action plan.

Implementation of the Hub, particularly in these early days, will be critical to ensuring its effectiveness, so seeing this and hopefully additional investment in its staffing and infrastructure will be key.

An Opportunity to Leverage the Newly Created Rare Disease Advisory Committee across CDER and CBER

In Frank and James’ 2018 proposal there was also a recommendation for the formation of a Rare Disease Advisory Committee, which would allow FDA access to experts in the science of small trials and other aspects of rare disease research.  As originally proposed, this new Committee could be convened in conjunction with the existing medical specialty area-focused advisory committees, akin to the Drug Safety and Risk Management Advisory Committee.

In December 2023, FDA established the Genetic Metabolic Diseases Advisory Committee (also called “GeMDAC,” which we blogged about here) to advise FDA regarding treatments for genetic metabolic diseases (i.e., those reviewed by the CDER Division of Rare Diseases and Medical Genetics). However, the expertise represented on the committee was to include small population trial design, translational science, and pediatrics, among others, which would be broadly applicable to rare diseases of other etiology. As such, there is an opportunity to leverage the GeMDAC in a similar fashion as the originally-proposed Rare Diseases Advisory Committee.

Earlier this month the FDA announced the first meeting of the GeMDAC will be held on August 2, 2024 to discuss a novel treatment for Niemann-Pick disease type C (and Frank and James are looking forward to being there!).

Next Steps for the Hub and Beyond

The FDA plans on holding an open public meeting this Fall, including a docket for public comment, to provide further information about the Agency’s vision for the Hub and receive feedback from the community to help shape the Hub’s priorities and initiatives.

According to FDA, the new Hub will have special focus on products intended for smaller populations and also for diseases where the natural history is variable and not fully understood. These are exactly the types of things that were addressed at ELF Scientific Workshop in May 2024 which addressed challenges in developing therapies for ultra rare diseases (see our blog about this here, which includes a link to the recording). In fact, at this Scientific Workshop, Frank called for the creation of an alternative effectiveness standard for ultra rare diseases that relies on all available scientifically valid evidence (e.g., clinical pharmacology/biomarkers, animal models, real-world evidence and other externally controlled comparisons [e.g., natural history studies]), not just evidence from adequate and well-controlled studies, which would be consistent with and further the mission of the Hub.

With the establishment of GeMDAC and the Hub (nearly in line with Frank and James’ 2018 proposal), we are eager to see whether sooner than 6 years from now there is a new alternative effectiveness standard for therapies to treat rare diseases where the feasibility of conducting a conventional adequate and well-controlled trial may be daunting or simply not possible (such as for products intended for smaller populations and also for diseases where the natural history is variable and not fully understood!). In the meantime, just as we never stopped advocating for both the Rare Disease Center of Excellence and the Rare Disease Advisory Committee (which are both now, in some fashion, a reality!), we are committed to continuing to help evolve sound regulatory science in order to bring more and better therapies to patients with rare, too often ultra rare, serious conditions.