FDA Grants MDA Kickstart Program Rare Pediatric Disease Designation and Orphan Drug Designation in Congenital Myasthenic Syndrome

According to a recent announcement, the FDA has granted the Muscular Dystrophy Association (MDA) Kickstart program both rare pediatric disease designation and orphan drug designation for congenital myasthenic syndrome (CMS) caused by choline acetyltransferase (CHAT) gene deficiency. This designation helps to encourage and facilitate the development of gene therapies for ultra-rare neuromuscular diseases, which typically have limited commercial appeal despite addressing significant unmet medical needs. ¹

"Receiving these important designations from the FDA for our pilot MDA Kickstart indication is an essential first step in supporting our ability to bring life-changing treatments to patients living with this rare disease," Sharon Hesterlee, PhD, chief research officer at MDA, said in a statement.¹ "This is a critical step toward fulfilling our mission to ensure that no patient is left behind in the era of genetic medicines."

The MDA Kickstart program, launched in 2023, is a novel initiative designed to bridge the therapeutic gap for neuromuscular diseases affecting fewer than 1000 patients in the United States. Its primary goal is to accelerate the transition from early-stage research to clinical trials, reducing risk and streamlining the development of gene therapies for ultra-rare conditions. The program's first project, initiated in September 2024 in collaboration with UC Davis and biomanufacturing partner Forge Biologics, focuses on CMS caused by mutations in the CHAT gene.

CMS linked to CHAT gene mutations is an extremely rare condition, with fewer than 250 known cases in the United States. It is characterized by severe muscle weakness and potentially life-threatening episodes of respiratory failure. Ricardo A. Maselli, MD, a neurologist at UC Davis Health, has developed a gene therapy that targets this condition by replacing the defective CHAT gene. This approach offers a promising therapeutic option for patients who currently lack approved treatments.

“For many of the young patients that I see in the clinic battling CMS, these designations are a crucial first step towards developing an effective therapy. These designations unlock a pathway to treatments that can profoundly change their lives and it's nice to see the FDA acknowledge CMS as a condition of unmet need,” Maselli, said in a statement.¹

In partnership with Forge Biologics, MDA will leverage advanced AAV gene therapy process and analytical development manufacturing services. All production activities will be conducted at Forge’s 200,000-square-foot cGMP facility in Columbus, Ohio, utilizing the company’s proprietary technology to ensure high-quality manufacturing standards.

"We are excited to support the MDA Kickstart Program and help advance these critical projects to the next stage of development through our leading AAV manufacturing expertise and services," John Maslowski, president and chief executive officer at Forge, said in a statement.¹ Collaborating with MDA embodies our mission at Forge to help deliver potentially life-changing treatments to patients."

Additionally, the rare pediatric disease designation granted to the MDA Kickstart program for CMS reflects ongoing federal efforts to incentivize the development of therapies for rare childhood diseases. However, the Priority Review Voucher program supporting these efforts is set to expire on December 20, 2024, unless Congress acts to extend it, underscoring the need for continued advocacy to maintain support for rare disease innovation.

"We’re proud to have made an impact with advocates for the reauthorization of the Rare Pediatric Disease PRV program as it is essential for continuing progress in rare disease treatment," Paul Melmeyer, MPP, executive vice president of public policy and advocacy at MDA, said in a statement.¹ "On September 10, an MDA contingent of more than 100 advocates urged lawmakers to extend this program so that more therapies, like the ones being developed through MDA Kickstart, can reach the patients who desperately need them. Their voices were heard and we’re extremely proud of this progress.”

“These designations enable us to synchronize a development plan with regulatory initiatives and incentives at an early stage.” Marina Kolocha, PharmD, PMP, project manager of the MDA Kickstart program, said in a statement.¹

At the 2023 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 19-22, in Dallas, Texas, Hesterlee chaired a session that presented an overview of the Kickstart program and its potential. The session also focused on opportunities to derisk gene therapies, the current barriers to furthering the development these agents, collaborative framework and data management.² After the session, Hesterlee sat down with NeurologyLive® to discuss the role industry plays in the commercialization of drugs and the cost of therapies for neuromuscular diseases compared with rare diseases. In addition, she also summarized a potential treatment for patients with CMS who experience episodic apnea.