By Dr. Bob Roth
A most interesting drug development issue is currently playing out in the media. Drug development companies and FDA have long struggled with finding the practical balance between costly development requirements and financial inducement so that innovation in medical care is promoted, especially for those diseases which are poorly treated with present options. The current situation with a novel neurologic drug for Amyotrophic Lateral Sclerosis (ALS) being developed by Genervon Biopharmaceuticals, LLC is an excellent case in point.
Genervon has requested that FDA consider their program according to the Accelerated Approval paradigm, and has taken their case to the public. Accelerated approval allows marketing of a drug that demonstrates an effect on a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality, or based on findings from a “surrogate endpoint” which is reasonably likely to predict clinical benefit. This pathway is particularly useful for diseases with a long time course such that a very prolonged clinical investigation would be needed to demonstrate clear evidence of efficacy. For the ALS indication, beneficial effects on a secondary efficacy endpoint such as quantitative lung function may be demonstrated relatively quickly whereas a mortality benefit would require a considerably longer investigation. Genervon believes they have evidence of such a secondary endpoint, and have also produced surrogate endpoint evidence using biomarkers which suggest beneficial effects on disease-related biochemical factors.
The fact that Genervon is requesting Accelerated Approval is not unexpected given the time and cost involved in ALS clinical investigation. Further, the clinical importance of the disease and utility of preliminary evidence for the potential of Genervon’s drug is supported by Fast Track status which was granted previously. What is quite novel about this situation is the media attention and FDA’s action to publish a Drug Information Update for ALS specific for the Genervon drug. Recognizing the great interest in the ALS community for any potentially new and useful therapies for this otherwise untreatable disease, FDA has publically requested that Genervon provide their clinical data for public evaluation. We suspect that this step by FDA, not part of the usual process, reflects the power of the patient advocacy voice. Previously, the principal role for patient advocacy in the drug approval process has been at the level of participation in Advisory Committee meetings rather than influencing FDA’s decisions about the applicability of the various abbreviated development programs.
The Genervon study is appropriately listed at the NIH’s publically available clinical trials site (www.clintrials.gov), though as is typical without presentation of study results. It is not clear exactly how FDA’s request to Genervon to make the study results publically available fits with the company’s request for Accelerated Approval apparently still pending.
Robert Roth, M.D., Ph.D., is Vice President and Worldwide Medical Director at The Weinberg Group, the world’s leading food and drug consulting firm. If you have any questions or thoughts on this blog post or others, please reach out to us by email.