Breakthrough designations granted by CDER's Office of Neuroscience in 2024

Many companies developing drugs for conditions with unmet needs have one urgent regulatory question: How—and how soon—can we get FDA Breakthrough Therapy Designation (BTD)? Sponsors know BTD can confer valuable benefits, including increased agency interactions and intensive guidance that could expedite development. They also know it often provides external validation to a company’s investors that, based on preliminary clinical data, an investigational product has shown significant potential to the FDA and for patients. At Parexel, we monitor the utilization of the FDA’s BTD program by tracking publicly announced BTDs. Between January 1 and September 30, 2024, nine biopharmaceutical companies announced BTDs for investigational neuroscience drugs.

Regulatory observations on the 9 BTDs granted by CDER’s Office of Neuroscience in 2024

• The number of BTDs granted for neurology and psychiatry drugs in 2024 provides some optimism:
  • To date, 9 BTDs have been granted this year, compared to 14 in the prior four years combined.
  • Additionally, we see BTDs granted for novel drugs intended to treat commonly occurring psychiatric disorders (such as lysergide d-tartrate for generalized anxiety disorder).
• BTD does not necessarily require novel efficacy or safety assessments. A substantial improvement in benefit as measured by usual endpoints (such as MADRS in depression trials) can support the designation.
• A demonstration of substantial benefit in a treatment-resistant population (such as DEEs, which are severe epilepsies characterized by drug-resistant seizures) can support BTD.
• The FDA may accept natural history studies (matched cohorts) as a comparator when considering BTD (as it did for diazoxide choline XR and delpacibart etedesiran).
• The FDA may grant BTD based on an agent's activity on disease biomarkers as long as the biomarker is an established surrogate for a clinically significant endpoint or is considered reasonably likely to predict clinical benefit (such as progranulin levels in FTD-GRN).
• Five of the nine drugs granted BTD in 2024 were for orphan indications, underscoring the FDA’s commitment to expediting the development of new products for rare conditions.

Contributing Experts