FDA Creates a New Advisory Committee for Genetic Metabolic Diseases – Could This Be an Opportunity to Support Rare Disease Product Development More Broadly?

December 14, 2023By Mark A. Tobolowsky & James E. Valentine & Charles G. Raver & Frank J. Sasinowski

On December 12, 2023, FDA announced the creation of a new advisory committee specifically for treatments for genetic metabolic diseases, the Genetic Metabolic Diseases Advisory Committee, or “GeMDAC.”  As described by FDA’s press release, genetic metabolic diseases are conditions whereby a genetic mutation, generally one that leads to dysfunction of a key protein or enzyme, disrupts the chemical processes (metabolism) responsible for converting food into energy and eliminating metabolic byproducts and waste from the body.  There are hundreds of known genetic metabolic diseases, most of which are rare and carry significant morbidity.

GeMDAC was established to advise FDA regarding treatments under the purview of CDER’s Division of Rare Diseases and Medical Genetics (DRDMG), within the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine.  Dr. Janet Maynard, Director of this Office, highlighted in the press release that “[g]enetic metabolic diseases include very rare diseases that individually affect a limited number of patients. Drug development for these conditions has unique and complex challenges, therefore few treatments are available to patients.”

GeMDAC’s mandate is to advise the Agency on these complicated issues in this challenging area of medical product development.  The advisory committee’s website notes that membership will be selected not just “from among authorities knowledgeable in the fields of medical genetics, [and] manifestations of inborn errors of metabolism” but also experts in “small population trial design, translational science, pediatrics, epidemiology, or statistics and related specialties” (emphasis added).  Note that FDA is currently soliciting applications to staff this committee.

Here at HP&M, we applaud this announcement and hope that it leads to a greater understanding of the challenges faced by rare disease patients, caregivers, and medical product developers, and, hopefully, to the successful development and approval of treatments for rare and ultra rare disease patients.  However, the challenges faced by these stakeholders are not isolated to products overseen by DRDMG alone.  Given that Dr. Maynard described that a primary focus of the advisory committee is for rare diseases, and its membership will include experts in the science of small trials, FDA’s establishment of GeMDAC creates an opportunity to support all rare disease drug development broadly, that is, not only for genetic metabolic conditions but rare diseases that fall under the purview of any FDA review division.

An Opportunity to Convene this New Advisory Committee for All Rare Disease Therapies

In 2018, HP&M attorneys Frank Sasinowski and James Valentine proposed a Rare Disease Center of Excellence (which we blogged about here).  The proposal outlined how a new Rare Disease Center of Excellence (COE) could leverage the skills of experts experienced in rare diseases to help expedite rare disease drug development across CDER, CBER, and CDRH, as well as other offices across FDA.  Importantly, the proposal also included a call to create a Rare Disease Advisory Committee, which could be called jointly with disease area-specific advisory committees to advise on the review of new products for any rare disease.  Members for this advisory committee would be selected “from among authorities knowledgeable and experienced in rare disease research and development.”

As the Agency fills out GeMDAC’s roster, particularly with those knowledgeable in the fields of small population trial design and other areas related to rare disease medical product development more broadly, it is a significant opportunity for FDA to leverage this expertise beyond products overseen by DRDMG.  The membership of the committee would not need to change beyond what FDA has proposed, nor would its primary mandate of serving DRDMG NDAs and BLAs.  However, there is tremendous potential in such a committee to advance rare disease drug development broadly.  GeMDAC could be used in conjunction with other advisory committees for rare disease products overseen by other divisions as well as CBER and even CDRH, as described in our 2018 proposal.  In addition, the rare disease experts included in GeMDAC’s membership could serve as ad hoc members of other advisory committees.

Volume of Genetic Metabolic Diseases Therapies Suggests Capacity to Serve Whole Agency

DRDMG was formed in 2020 as part of the CDER Office of New Drugs reorganization, so it is a fairly new Division.  However, our research reflects that of the orphan-designated novel drugs approved since 2013 by DRDMG or its predecessor, the Division of Gastroenterology and Inborn Errors Products (DGIEP), only 1 out of 18 went to an advisory committee meeting.  The online records of the Gastrointestinal Drugs Advisory Committee, the advisory committee of choice for DRDMG/DGIEP prior to the establishment of GeMDAC, only list 7 meetings total in these 10 years, likely none of which would have been in DRDMG after the split (e.g., irritable bowel syndrome, primary biliary cholangitis).

Presumably, the Agency foresees greater use of advisory committees in the future for genetic metabolic disease products, but this still leaves significant bandwidth and potential to address rare disease issues more broadly.  Meanwhile, other Divisions have referred a multitude of rare disease drugs to other advisory committees with issues on which the proposed constituency of GeMDAC, with its rare disease expertise, would be well-positioned to provide meaningful advice.

Again, we heartily applaud CDER’s creation of GeMDAC.  It is a significant step forward for rare disease patients whose diseases bring them within the oversight of DRDMG.  In addition, many other rare disease patients could (and we hope WILL) benefit from this committee’s expertise, so long as FDA extends the reach of GeMDAC to benefit all rare disease patients, and not only those with genetic metabolic conditions.