Alkermes has been hit hard by the FDA’s rejection of antidepressant candidate ALKS 5461 – citing a lack of evidence that it was clinically effective.
The US regulator issued a ‘refusal to file’ letter to the company yesterday for the drug, which is a fixed-dose combination of buprenorphine, an opioid used for many years to treat addiction, and samidorphan, a new mu-opioid receptor antagonist. Shares in the company closed down more than 20% after the decision.
Despite a clinical efficacy and safety package with data from more than 30 clinical trials and around 1,500 patients with major depressive disorder (MDD), the FDA has said it wants to see “additional well-controlled trials” plus a bioavailability study – likely setting the programme back a lengthy period. Analysts at Jefferies have put a possible launch date for the drug back to 2021 from 2019.
Alkermes is unhappy about the decision, saying the FDA gave no indication that it had issues with the level of evidence included in the dossier. The rejection doesn’t come out of the left field however as the AKLS 5461 trials programme saw two phase III failures in 2016 in the FORWARD-3 and FORWARD-4 studies, with Alkermes’ dossier relying on a third positive trial to prop up the overall data set. The company maintained that the negative trials were scuppered by a larger-than-expected placebo response.
Alkermes was hoping that the massive unmet need in patients with MDD would help sway the FDA. Despite the large number of approved agents, the majority of MDD patients treated with standard antidepressants do not achieve adequate relief.
According to the company, there’s been minimal progress in developing antidepressants with novel mechanism of action since the introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine 30 years ago. Currently patients with an inadequate response to first-line medications have limited options.
Alkermes does have another phase IIIb clinical trial ongoing with ALKS 5461, but the company’s CEO Richard Pops said until the FDA’s specific concerns about the deficiencies in the file are revealed there is no guarantee that will answer the regulator’s concerns.
“Alkermes strongly disagrees with the FDA’s conclusions and plans to appeal the FDA’s decision,” said the company in a statement.
The setback for ALKS 5461 will leave Alkermes more reliant on a positive read-out for schizophrenia candidate ALKS 3831, with two phase III trials due to report later this year.
The company said it is evaluating the impact of this update on its financial guidance for 2018.