Alkermes has cleared the first major hurdle in its bid to advance schizophrenia candidate ALKS 3831, showing an improvement over placebo in its first phase 3 trial—but a much bigger test is still to come.
The oral antipsychotic candidate combines olanzapine—currently the third-most prescribed drug for schizophrenia—with an opioid antagonist that is designed to alleviate some of olanzapine's side effects.
Olanzapine is known to cause weight gain and metabolic changes that could elevate the risk of Type 2 diabetes, and as a result the drug is no longer recommended as a first-line therapy in treatment guidelines. Alkermes hopes to counteract these by adding its samidorphan compound to the formulation.
ENLIGHTEN-1 was a four-week, hospital-based study that compared ALKS 3831 to placebo and olanzapine in patients with acute schizophrenia, measuring efficacy using the widely used Positive and Negative Syndrome Score (PANSS) rating scale as well as physician assessments.
Alkermes says its drug performed significantly better than placebo in reducing PANSS scores and physician impression ratings at week four. It also showed a numerically superior improvement compared to olanzapine—something that was also observed in its phase 2 trial of the drug—although this wasn't statistically significant.
"I don't want to overstate this finding, but this is the second study in which we have observed his trend and we're going to continue to investigate this as we move beyond the top-line data," said Elliot Ehrich, M.D., Alkermes' vice president of R&D, on a conference call.
Both ALKS 3831 and olanzapine groups gained weight in ENLIGHTEN-1, but that was likely to be a result of the higher level of care and nutrition that goes hand in hand with hospitalization for acute schizophrenia.
So far so good, but the acid test for Alkermes will come when it unblinds the ENLIGHTEN-2 study—comparing the new drug to olanzapine on weight gain and metabolic parameters over six months—sometime next year.
"This data set will determine the potential market opportunity of 3831," said Jefferies analysts in a research note. "In our view we would need to see at least a 15% relative improvement in weight gain vs olanzapine for physicians to choose 3831."
Before then however Alkermes is expecting some readouts from a phase 1 trial that will give some initial comparisons on those side effects. It has also started a study to see if ALKS 3831 can avoid the glucose monitoring requirement of olanzapine, with results due later this year, as well as a study in 250 young adults who it believes are more susceptible to weight gain with olanzapine that should read out in early 2019.
"We're moving ahead full steam … and look forward to the exciting data readouts ahead of us," said Richard Pops, Alkermes' CEO, on the call.