Alkermes has started a rolling application to market its twice-failed antidepressant ALKS 5461, hoping that the sum of all its clinical evidence will be enough to convince the FDA of its value.
ALKS 5461 is remarkable in that it has a completely new mechanism of action, unlike the current array of drugs for major depressive disorder (MDD). If approved, it could open up a new line of treatment for people—estimated to be in the millions worldwide—who struggle to control symptoms despite drug therapy.
The decision follows a pre-New Drug Application (NDA) meeting with the FDA that set up the company to file with a dossier based on more than 30 clinical trials, including the positive FORWARD-5 trial and two earlier studies that failed to hit the mark because of what Alkermes said was a high placebo response.
Overall, the dataset shows "consistent efficacy and safety profile of ALKS 5461 demonstrated throughout the entirety of the development program," according to Alkermes Chairman Richard Pops.
While the FDA has agreed to accept the rolling NDA, Alkermes still has some way to go before it can be anything more than optimistic about approval. Unlike the earlier FORWARD-3 and FORWARD-4 trials, FORWARD-5 relied on averaging out Montgomery-Åsberg Depression Rating Scale (MADRS) scores, which the firm believes is a more accurate way of showing how well a drug is working over time. There is no guarantee however that the FDA will be happy to look at the data in that way, however.
Also, Alkermes' trials program for the drug has used sequential parallel comparison design (SPCD), which can be used to reduce the confounding effect of a high placebo response, which is a commonly cited issue in trials of psychiatric medicines. According to Pops, the ALKS 5461 NDA will also be the first to be reviewed by the FDA based on SPCD efficacy analysis.
Analysts at Leerink said in a recent research note that there are "multiple approvability questions" for the new drug, particularly the tweaked FORWARD-5 endpoint and novel trial design, although they also suggested that the FDA has shown flexibility when considering drugs for poorly served psychiatric conditions.
ALKS 5461 is a once-daily pill combining samidorphan and buprenorphine, a centrally acting opioid modulator, and thanks to its novel mechanism has picked up a fast-track designation from the FDA for its potential to address an unmet medical need.
"The initiation of the rolling submission for ALKS 5461 is an important first step in the registration process for ALKS 5461, as we work to bring this potential new medicine to patients suffering from major depressive disorder," said Elliot Ehrich, M.D., Alkermes' R&D head.
"We expect to complete the submission of the NDA by year-end 2017 and will continue to collaborate closely with the FDA as we work expeditiously toward making ALKS 5461 available to patients and their healthcare providers."