Caplyta achieves second Phase III success in depression

Intra-Cellular Therapeutics' antipsychotic drug Caplyta (lumateperone) has demonstrated significant effectiveness in treating major depressive disorder (MDD). This was evidenced by a second successful Phase III trial, which occurred just two months after its initial success. These results enhance Caplyta’s profile as a promising new option for MDD treatment, potentially leading to substantial market success.

In a study known as Study 502, involving 480 participants, Caplyta met its primary and key secondary endpoints when used alongside standard antidepressants. The 42mg dose of Caplyta resulted in a 4.5-point reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS) after six weeks, compared to a placebo. In total, patients on Caplyta showed an improvement of 14.7 points on the MADRS scale, whereas those on placebo showed an improvement of just 10.3 points.

CEO Sharon Mates expressed optimism about Caplyta's potential, stating that these results support the drug as a leading option for treating mood disorders. The recent success builds on the findings from April's first Phase III trial, Study 501, where Caplyta also proved effective, showing a 4.9-point advantage over placebo.

With these favorable outcomes, RBC Capital Markets analyst Brian Abrahams predicts a clear path toward approval and commercialization in the MDD market. This could potentially add $1.7 billion in revenue for Caplyta, boosting its total U.S. sales to more than $3 billion annually. Initially approved by the FDA in 2019 for schizophrenia and later for bipolar depression in 2021, Caplyta is a butyrophenone-class atypical antipsychotic administered as a once-daily oral treatment.

Abrahams further suggested that the strong, consistent data might increase the drug’s market value, potentially making Intra-Cellular Therapeutics an attractive buyout target. Christoph Correll, a key opinion leader, indicated optimism for Study 502 outcomes based on the data from Study 501. He also mentioned that Intra-Cellular likely wouldn’t need results from a third trial, Study 503, which is focused on long-term safety, before pursuing a label expansion.

Intra-Cellular Therapeutics plans to submit a supplemental new drug application for Caplyta in MDD during the second half of the year. The drug's favorable safety profile further strengthens its case. Combined safety data from Studies 501 and 502 indicated mostly mild-to-moderate side effects such as dizziness, dry mouth, somnolence, and nausea, all of which resolved during the trials. Importantly, the absence of metabolic issues like weight gain could set Caplyta apart from other antidepressants like AbbVie’s Vraylar (cariprazine) and Rexulti (brexpiprazole) from Otsuka and Lundbeck.

Correll predicted that Caplyta might take market share from Vraylar and Rexulti. Efficacy data showed that Vraylar improved symptoms by 2.1 to 2.6 points on the MADRS scale compared to placebo, while Rexulti showed an improvement of 2 to 3.2 points.

Overall, Caplyta's success in the recent trials positions it as a potential game-changer in the treatment landscape for MDD, offering a new, effective option with a favorable safety profile.