Newly released FDA data and approvals signal a more welcoming regulatory environment for neuroscience clinical trials

As 2023 advances, so too does the evidence that we have entered a new era in the FDA regulatory environment for neurology and related therapies. Across approval and development decisions in difficult conditions such as Alzheimer’s, ALS, Duchenne, and limb-girdle muscular dystrophy, a new FDA willingness to accept the greater uncertainties associated with accelerated approval and surrogate endpoints seems apparent.

But as the regulatory landscape tilts in favor of the neurosciences, and patients, industry, investors, and researchers adjust to this regulatory inflection point, how poised is the neuro R&D pipeline to respond?

Neuroscience Trials 2020 - 2022.jpg

Our analysis of Center for Drug Evaluation and Research (CDER) data indicates that neurology novel approvals outnumbered cancer novel approvals in the first half of 2023. Although clinical trial starts across all therapeutic areas were down overall last year, CNS clinical trials starts were still relatively high compared to previous FDA data (considering clinical trial disruptions due to COVID-19). Active neuroscience trials show continued growth, with an increase of 16% from 2020-2022. This includes an increase in neurodegenerative/ movement/ neuromuscular trials by 24.1% and an increase in psychiatry trials by 17.6% from 2020-2022.

Although there was a slight pause in 2022 for neuroscience clinical trial starts, this followed a surge in activity during 2021, with neurodegenerative/movement/neuromuscular starts soaring by 75%. Neurology starts for TBI, migraine, seizures, and epilepsies increased by 47%, with psychiatry jumping up by 65% in 2021. 

Neuroscience clinical trials, perhaps the only therapeutic area rivaling oncology in terms of patient unmet needs, have often faced high development costs, lower clinical development success rates, and a longer and less certain road to regulatory approval. The science hasn’t always provided the endpoints necessary to instill confidence with the FDA, and achieving accelerated approval was often met with controversy.  

But more recently, the FDA has taken a different posture, showing confidence in surrogate endpoints for accelerated approvals, as shown by the April 2023 approval of an ALS treatment (tofersen) on the basis of a surrogate endpoint. Although tofersen is the third drug approved for ALS in the last six years, it is the first ALS treatment ever approved through the accelerated approval pathway. Prior to this, in September of 2022, approval of Relyvrio was also granted by the FDA, reflecting forward-thinking regarding drug effectiveness for neurodegenerative diseases. 

Another positive regulatory move occurred in June 2023, when CBER Director Peter Marks, MD, overruled his CBER review team to grant accelerated approval for Elevidys, a Sarepta gene therapy for treating Duchenne Muscular Dystrophy within a narrow pediatric patient population (children 4-5 years old). 

In a CBER FDA Memo, Marks outlined his decision, agreeing with the review team’s conclusions regarding product quality and safety but disagreeing with certain interpretations of the efficacy data. Accounting for the totality of the available evidence and noting the high unmet medical need in a serious disease affecting a relatively small number of individuals, Marks stated that the data demonstrates an effect on the surrogate endpoint that is reasonably likely to predict clinical benefit in the specific population of individuals ages 4 through 5 years.1

The FDA’s conversion of lecanamab’s accelerated approval for Alzheimer’s into a conventional approval in July 2023 also signified an important milestone, validating the amyloid hypothesis, a defining pathophysiological feature of the disease. Approval was based on phase II biomarker data, not on clinical benefit, despite ongoing industry debate on the limitations of a drug’s effect based on biomarkers.

These advancements along with BridgeBio’s July 2023 announcement of the FDA’s intention to consider accelerated approval for a limb-girdle muscular dystrophy therapy based on a new surrogate endpoint (glycosylated alpha-dystroglycan levels), reflect an unprecedented openness to change and a forward-thinking momentum in the field. This is especially critical in scenarios that hinge on smaller, fewer studies, as in the case of Reata’s approval for the treatment of Friedreich’s ataxia, the first-of-its-kind in that it is based on just a single study, focusing on the same set of patients over time.

Even beyond recent accelerated approvals, the FDA has seemingly become more open to RWE in support of submission packages, especially in rare, progressive, neuromuscular disease cases. 

Although the field has faced great setbacks in the past and neuroscience remains one of the most challenging areas for clinical development, recent advancements and investments in the field signal a changing regulatory and clinical development landscape. This requires smarter development strategies, a patient-focused mindset, and proactive engagement with regulators. 

As we navigate these changes, we anticipate different hurdles, but our focus remains the same – adapting to change and harnessing new opportunities to advance our understanding of neuroscience and develop new therapies where there is a great unmet patient need.

1Center Director Decisional Memo - ELEVIDYS (, CBER Director Peter Marks, MD, June 2023

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