- New clinical results are helping make the case that an antipsychotic from Alkermes is more effective than a rival drugmaker's former blockbuster treatment.
- The key Phase 3 trial, one of two in the ENLIGHTEN program, pitted the Dublin-based pharma's ALKS 3831 against placebo in more than 400 patients demonstrating acute exacerbation of schizophrenia. After four weeks, participants taking the investigational drug showed significant improvement on the Positive and Negative Syndrome Scale (PANSS) versus placebo.
- The study also had a comparator arm that administered olanzapine, the active ingredient in Eli Lilly's Zyprexa and the third most prescribed antipsychotic for schizophrenia, according to Alkermes. Olanzapine therapy resulted in a similar PANSS score reduction compared to the control group, but at a p-value of 0.004 — higher than the 0.001 observed with ALKS 3831.
Alkermes' aim with ALKS 3831, a mixture of samidorphan and olanzapine, is to show it's just as effective as the latter drug alone, but with a better safety profile. Zyprexa, for instance, carries both a black box warning for increased mortality in elderly patients with dementia-related psychosis, and its label also warns about the potential for weight gain and metabolic disorders.
On the effectiveness front, ALKS 3831 and olanzapine both led to significantly lower scores on PANSS, a tool used to determine the severity of schizophrenia symptoms, compared to placebo. Yet, Alkermes touted the slightly higher numerical difference between its drug and the control arm over that of olanzapine and the control arm.
"The difference was not statistically significant and the analysis is exploratory so I don't want to overstate this finding, but this is the second study in which we have observed this trend and we're going to continue to investigate this," Elliot Ehrich, Alkermes' head of R&D, said during a June 29 investor call.
Perhaps more importantly, though, are the possible safety disparities. Topline results only revealed that both ALKS 3831 and olanzapine treatment resulted in dry mouth, sleepiness and weight gain, and the company disclosed little more during the investor call. Another late-stage study, ENLIGHTEN-2, is looking at how the two drugs affect weight gain, and should have data coming out in the first half of 2018.
"This dataset will determine the potential market opportunity of 3831," investment bank Jefferies said in a June 29 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."
In ENLIGHTEN-1, Alkermes' drug also hit the key secondary endpoint, with patients demonstrating better scores on the Clinical Global Impression – Severity (CGI-S) scale versus placebo. Across the ALKS 3831, olanzapine and control arms, 91%, 89% and 83% of patients persisted to the end of the study.
Alkermes plans to reveal more complete data from the trial at a later medical meeting.
The schizophrenia space has already proven profitable for Alkermes. The company launched the original version of the antipsychotic Aristada (aripiprazole lauroxil) in October 2015, and an extended release injection earlier this month. Net sales in 2016 for Aristada reached $47 million.
Zyprexa, which fell off patent protection in the U.S. several years ago, continues to be a big revenue generator. The drug brought in $725 million last year, though non-stateside sales represented more than 90% of that total.