Intra-Cellular Therapies has unveiled another positive late-stage trial readout for Caplyta, taking another step toward a potential blockbuster label expansion for the depression drug.
In what CEO Sharon Mates, Ph.D., called an “overwhelmingly positive” study, Intra-Cellular said Caplyta significantly bested placebo at improving depression severity when used as an adjunctive therapy on top of existing antidepressants in patients with major depressive disorder (MDD).
Specifically, on a clinician-administered questionnaire called the Montgomery-Åsberg Depression Rating Scale (MADRS), Caplyta led to an average 4.9-point reduction compared with placebo at Week 6, the phase 3 Study 501 showed.
Caplyta is currently approved for schizophrenia and bipolar depression. MDD represents a much larger patient population—and a more competitive market—that’s about three times that of bipolar depression, according to analysts at Leerink Partners. An approval in MDD could give Caplyta at least $1 billion in additional peak sales, the analysts said in a note in January.
Caplyta’s data appear competitive to those from AbbVie’s Vraylar in their respective clinical trials. AbbVie CEO Rick Gonzalez has previously put Vraylar’s peak sales potential at $4 billion.
In Vraylar’s phase 3 trial as an adjunctive MDD therapy, two different dosage strengths of the drug posted 2.4- and 2.9-point MADRS improvements over placebo at Week 6. Notable efficacy emerged at the one-week point for Caplyta, whereas Vraylar’s advantage over placebo only started to show after two weeks.
Such cross-trial comparisons should be viewed with a grain of salt because of different trial designs and patient characteristics, but industry watchers and doctors rely on them anyway to make projections and treatment decisions, respectively.
Besides the clinician-administered MADRS score, Caplyta also demonstrated a statistically significant reduction on the patient-reported Clinical Global Impression Scale for Severity of Illness (CGI-S) score compared to placebo at Week 6, according to Intra-Cellular.
On the safety side, commonly reported adverse events for Caplyta included dry mouth, fatigue and tremors. The problems were mostly mild to moderate and resolved within a short period of time, Intra-Cellular said.
The latest Study 501 results followed another positive phase 3 report last year from Study 403 in MDD or bipolar depression patients with mixed features.
Because Study 501 also allowed some patients with psychotic features, one analyst on a Tuesday conference call wondered whether those patients could have driven the overall benefits for Caplyta. The Intra-Cellular team refuted that possibility, noting that those patients only made up a small, single-digit percentage proportion of the overall trial population.
Now, Intra-Cellular is waiting for a readout from a third phase 3 trial, Study 502, which is expected by the end of June. While Study 501 is a global trial, Study 502 is being conducted in the U.S. alone. Besides that feature, the two studies are very similar if not exactly the same, Mates noted.
“The first thing we’re going to do is get that data,” Mates said on an investor call Tuesday. “We will then go to the FDA, with both studies, and all of our supporting studies, which includes our mixed features [study].”
Intra-Cellular has already shared the mixed features data with the FDA. Pending the Study 502 data, the company now plans to file for MDD with the FDA this year, Mates said. It remains unclear whether the company needs to submit two separate applications for MDD and mixed features.
Should Caplyta be approved in MDD, Intra-Cellular plans to increase its current sales force to target more primary care physicians, Leerink analysts noted in a March note after hosting the company’s execs at its investor event.
On Tuesday’s call, Mates said the company will talk more about its commercialization plan on its next quarterly earnings call.
Riding a 23% stock-price jump thanks to the positive readout, Intra-Cellular on Tuesday announced a $500 million stock offering to help fund its operations, including commercialization of Caplyta and advancement of its R&D pipeline.
Editor's Note: The story has been updated to include information about Intra-Cellular's $500 million stock offering.