Alkermes has suffered a major setback in its late-stage pipeline after depression candidate ALKS 5461 failed pass muster in two late-stage trials.
The Ireland-domiciled company insists it is not giving up on its lead drug development project, however, and says it will press on with a third phase III trial in the hope of showing a benefit of the drug.
The two phase III trials – FORWARD-3 and FORWARD-4 – involved patients with major depressive disorder (MDD) who had failed to respond to established antidepressants.
ALKS 5461 failed to show an improvement over placebo in both studies, although Alkermes said there was a trend towards efficacy in FORWARD-4, while an unexpectedly high placebo response in FORWARD-3 may have masked any benefit for the drug.
Now, the company says it will step up enrolment of patients into a third trial – called FORWARD-5 – in a bid to improve the chances of demonstrating a positive result.
If that occurs, Alkermes said bundling that dataset with a successful phase II trial and the FORWARD-4 results could be enough to build a marketing application for ALKS 56461.
“We are building a large body of evidence supporting our belief in the clinical utility and the novel mechanism of action of ALKS 5461,” said Alkermes’ chief executive Richard Pops.
“We await the results of FORWARD-5 and will determine our next steps along the regulatory path with those results in hand.”
Investors seemed to be unswayed by the reassurances coming from Alkermes’ management and voted with their feet yesterday, driving the company’s share price down almost 45% yesterday, wiping around $4bn off the value of the company.
ALKS 4561 is a once-daily oral formulation of two drugs – mu opioid receptor antagonist samidorphan and mixed mu agonist/kappa antagonist buprenorphine – and represents a completely new approach to treating depression.
Buprenorphine is thought to have antidepressant effect via the kappa receptor, but its stimulation of the mu receptor means it has abuse potential. This is overcome by giving it alongside samidorphan.
Samidorphan is also being tested in combination with olanzapine in schizophrenia in a product known as ALKS 3831, which is in phase II trials. The aim of the combination is to preserve the therapeutic effects of olanzapine but avoid weight gain, a key side effect of the drug.
Alkermes is in the throes of launching its new long-acting schizophrenia treatment Aristada (aripiprazole lauroxil), which was approved by the FDA in October.
However, the scale of the sell-off reflects the importance attached to the ALKS 5461 project, which some analysts had previously suggested could become a $500m product at its peak.