New FDA Guidance Documents for Drug Development in Neurological Conditions Aiming to Ease the Drug Approval Paths

This month, we saw FDA issued five guidance documents for drug development in five different neurological conditions/diseases (Alzheimer’s disease, DMD, ALS, Migraine, and Pediatric epilepsy). These newly issued guidance documents are intended to ease the drug approval requirements or offer the charities for the drug development pathway.

We think that this is a general trend in FDA and we expect that the similar guidance documents will be issued for other conditions/diseases aiming to ease the requirements for drug development – eventually speed up the drug development process, and the innovative drugs available to patients.

According to Statement from FDA Commissioner Scott Gottlieb, M.D. on advancing the development of novel treatments for neurological conditions; part of broader effort on modernizing FDA’s new drug review programs

“Today I’m pleased to issue five guidance documents that benefited from the streamlined approach of this pilot as part of a broader, programmatic focus on advancing treatments for neurological disorders that aren’t adequately addressed by available therapies. These guidance documents provide details on how researchers can best approach drug development for certain neurological conditions – Duchenne muscular dystrophy (DMD) and closely related conditions, migraine, epilepsy, AD and ALS. These guidance documents provide our current thinking and sound regulatory and scientific advice for product developers so that safe and effective treatments can ultimately be made available to patients. These documents are each a culmination of thoughtful scientific collaboration within the agency and incorporate important input from patients, researchers and advocates. We hope that providing up-to-date, clear information about our scientific expectations, such as clinical trial design and ways to measure effectiveness, will save companies time and resources and ultimately, bring effective new medicines to patients more efficiently.”

Below is a table to summarize the key points from these five guidance documents:

Indication	Guidance Title	Key Points
Alzheimer's disease	Early Alzheimer’s Disease: Developing Drugs for Treatment	No longer requiring co-primary efficacy endpoints to show the benefit in both cognitive and functional (or global) measures Staging the AZ as four different stages accepting different endpoints for different stages Allowing biomarker effects to be the primary endpoint in patients with Alzheimer pathology but no current symptoms
Duchenne muscular dystrophy (DMD) and related conditions	Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment	Emphasizing the difficulties in designing trials of drugs for these conditions.  Efficacy endpoints, which basically leave it up to individual study sponsors to discuss with FDA staff the best approach on a case-by-case basis the DMD guideline did not do, is open a path for approval based solely on biomarker effects such dystrophin levels in muscle, although, effects on objective measures such as respiratory and cardiac muscle function can be used to support approval.
Amyotrophic lateral sclerosis (ALS)	Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment	Offering more clarity Efficacy must be demonstrated at "clinically meaningful" levels for symptoms, function, or survival -- period
Migraine	Migraine: Developing Drugs for Acute Treatment	Sponsors would no longer be required to conduct trials addressing four different classes of symptoms: pain, nausea, photophobia, and phonophobia. Trials will only need two primary endpoints: pain reduction and effects on individual patients' "most bothersome symptom."
Pediatric epilepsy	Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Efficacy from Adults to Pediatric Patients 4 Years of Age and Older	For drugs intended for children age 4 and older with partial onset seizures, the FDA will no longer require that efficacy trials be conducted in children. The agency will now consider efficacy data from adult patients to be sufficient for pediatric approval.