The Food and Drug Administration (FDA)’s Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 21 to 2 that the benefit-risk profile of ALKS 5461 was not adequate to support approval. ALKS 5461 is an investigational adjunctive treatment for major depressive disorder (MDD) in patients with an inadequate response to standard antidepressant therapies.
ALKS 5461 is a once-daily, oral medicine that acts as an opioid system modulator. It consists of a fixed-dose combination of buprenorphine (BUP), a partial mu-opioid receptor agonist and kappa-opioid receptor antagonist, and samidorphan (SAM), a mu-opioid receptor antagonist.
In the meeting documents, the panel presented a scenario which illustrated their concerns regarding potentially complex drug interactions that may occur in the population for which the drug is intended. “Consider the following hypothetical scenario of a patient taking BUP/SAM as adjunct therapy for major depression who develops back pain. The patient might be prescribed an opioid analgesic by a primary care or emergency department provider, or might even obtain opioids from a friend or family member. If BUP/SAM reduces the analgesic efficacy of the opioid, the patient may increase the dose in an attempt to achieve adequate pain control. However, if the µ-opioid antagonist effect diminishes or the patient misses doses or discontinues BUP/SAM while taking this high dose of opioid, he or she could be at increased risk for respiratory depression and overdose from the now unopposed full opioid agonist, particularly if also using benzodiazepines or other CNS depressants.”
Alkermes’ Chief Executive Officer Richard Pops said that the Company was “disappointed and surprised” with the outcome of the committee vote. The NDA included data from more than 30 clinical trials involving >1500 patients with MDD. “[We] will continue to work with the FDA as it completes its review of the ALKS 5461 regulatory submission,” said Pops.
The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date for the ALKS 5461 New Drug Application (NDA) for January 31, 2019.
FDA advisory committees are made up of independent experts who provide recommendations to the Agency regarding potential new treatments. Their decisions are not binding but their recommendations are considered when the FDA reviews NDAs.
For more information visit FDA.gov.