Comments on Depressive Disorder Guidance
The National Alliance on Mental Illness (NAMI) says an FDA draft guidance on developing drugs to treat major depressive disorder “is long overdue. It is important for the agency to take steps to improve the drug review process and ensure greater transparency and improvement about the review process…. This guidance is an important first step, but more effort is needed to ensure alignment with the advances in patient-focused drug development that were mandated by the PDUFA V and VI agreements and the 21st Century Cures Act.”
NAMI’s comment letter says the group is concerned that the draft guidance does not contain any reference to patient-focused drug development as a critical element of the drug review process. The draft also appears to lack a focus on innovative trial design or structured risk-benefit framework that were part of both PDUFA VI and 21st Century Cures, it says. It asks that the final guidance explore both additional primary and secondary endpoints and include language encouraging development of novel therapies beyond existing categories.
Janssen’s letter says it would be helpful if the final guidance provided advice to help ensure that study designs are rigorous while making the path to approval more efficient. Specifically, it says, the updated guidance should encourage sponsors to implement promising new methodologies in development programs and show a clear regulatory pathway towards acceptance of novel endpoints.
“Recognizing recruitment challenges and high unmet need for safe and more effective treatments for pediatric and adolescent patients with major depression,” the letter says, “Janssen requests the agency to consider innovative approaches and flexibility in the required number of adequate and well-controlled short-term clinical studies in these patient populations.” The company also provides specific line-by-line comments.
Boehringer Ingelheim says it welcomes the high level of harmonization between the draft guidance and the current European Medicines Agency guideline allowing for multi-regional development programs ensuring the timely availability of novel drugs to patients in need globally. The company also says it welcomes the openness for novel approaches, such as development of drugs with fast onset of action.
Takeda’s comment recommends flexibility to design clinical trials for this patient population and not restrict them to monotherapy. “Digital health technologies are being used to collect real-world patient data so it would be helpful for FDA to provide guidance,” the comment says. “The draft guidance should provide specific recommendations to develop and use digital technologies to collect patient data in clinical trials that can be used in regulatory decision-making and labeling.” And it recommends that the draft address development strategies for an antidepressant to demonstrate an effect on specific symptoms.