Denali, Neurogene among FDA picks for 'Operation Warp Speed' rare disease efforts

In September 2023, the FDA unveiled the Support for Clinical Trials Advancing Rare Disease Therapeutics pilot program, or START. This initiative aims to expedite drug development for rare diseases by providing selected companies with frequent interactions and guidance from FDA staff. These interactions are focused on aiding study design, patient selection, and product characterization. Participants collaborate with the FDA to establish milestones and success metrics.

The selection process involved criteria from the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER), with each center empowered to choose up to three sponsors. CBER sought sponsors developing cell or gene therapies for rare conditions that can cause severe illness or death before age 10. Conversely, CDER focused on sponsors with treatments for rare neurodegenerative diseases.

Among the companies selected for the START program are Denali Therapeutics, Neurogene, Larimar Therapeutics, and Grace Science, each announced on June 3.

Denali Therapeutics is advancing its program to tackle mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A. This genetic neurodegenerative lysosomal storage disease results from a missing enzyme due to a gene mutation. Their candidate, DNL126, aims to replace this enzyme and is currently undergoing a phase 1/2 clinical trial.

Neurogene is participating with NGN-401, a gene therapy designed to treat Rett syndrome, a genetic disorder that impedes brain development in young girls. NGN-401 is also in a phase 1/2 trial, with interim data anticipated later this year.

Larimar Therapeutics' contribution to the START program is nomlabofusp (CTI-1601), aimed at Friedreich’s ataxia, a genetic disorder affecting mobility and cognition beginning in late childhood. Interim data from an ongoing phase 2 trial are expected by the fourth quarter of 2024.

Grace Science has introduced GS-100, a gene therapy addressing NGLY1 deficiency, an extremely rare disorder causing various neurological symptoms from early childhood. Grace Science has treated two patients with GS-100 in a single-arm, dose-finding phase 1/2/3 trial, with a third patient set to receive treatment later this summer. Carolyn Bertozzi, Ph.D., co-founder of Grace, expressed optimism about the therapy's potential to transform drug discovery and development, stating that the START program could improve the lives of patients suffering from NGLY1 deficiency and pave the way for treating other rare and common diseases.

The FDA's START program might soon announce additional participants. According to an email from CBER, four participants have been chosen for the pilot, while CDER has selected three. Following the evaluation of the initial cohort, a second pilot group with more participants may be launched, the FDA indicated.

This initiative represents a concerted effort by the FDA to accelerate the development of therapies for rare diseases by fostering closer collaboration between the agency and pioneering biotechnology companies. The hope is that such a program will not only bring effective treatments to market more swiftly but also set a precedent for future drug development endeavors.