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‘No holes to poke:’ Intra-Cellular’s Caplyta delivers sweeping win in depression trial

While forging ahead in this year’s #FierceMadness Drug Ad Tournament, Intra-Cellular Therapies’ Caplyta has ginned up what analysts view as a sweeping trial win in two distinct mood disorders.

Caplyta’s phase 3 data in mood disorder patients with mixed features were “unequivocally good,” leaving “no holes to poke,” Mizuho analyst Graig Suvannavejh, Ph.D., said in a Wednesday note to clients.

Analysts at SVB Securities shared similar optimism. Tested as a monotherapy, Caplyta demonstrated “consistently significant effect, rapid onset of action and large effect size” on all endpoints in Study 403, the team said in a Tuesday note.

The trial is evaluating Caplyta in treating depression episodes in mixed features patients with either major depressive disorder or bipolar depression. Both patient subgroups benefited from the treatment, the SVB team noted.

Caplyta, as an atypical antipsychotic, is currently approved in the U.S. to treat schizophrenia. It’s also endorsed as a monotherapy and as an adjunctive therapy for depressive episodes associated with bipolar depression.

“Strong,” “robust” and “favorable” were the words analysts from other institutions used to describe the Study 403 data during an Intra-Cellular conference call on Tuesday.

But compared with the trial’s seemingly overwhelming success, Caplyta’s regulatory path for a new indication in mixed features depression is not as clear. As Mizuho’s Suvannavejh pointed out, no precedent exists for an indication in mixed features depression.

During Tuesday’s call, analysts repeatedly pressed Intra-Cellular’s management for guidance on its FDA filing plan and whether additional data will be needed to get an approval in mixed features depression. But Sharon Mates, Intra-Cellular’s chair and CEO, said the company is still only gathering the data to request a meeting with the FDA.

“I think that we can ask the question in any way we like, and the answer is still the same: We need to go to the FDA and talk to the FDA, and determine the next steps for the program,” Mates said.

“We are very pleased with the fact that we have shown that [Caplyta] has a very broad breadth associated with it, that we believe that it’s possible to treat across many of the mood spectrum disorders,” the CEO added.

On the primary endpoint of Study 403, Caplyta 42mg given once daily significantly reduced the severity of depressive episodes compared with placebo as measured by the MADRS score. The trial’s patients had a mean baseline MADRS of about 31, and Caplyta on average led to an additional 5.7-point reduction versus placebo.

The average reduction in patients with bipolar depression and major depressive disorder was 5.7 points and 5.9 points, respectively.

Caplyta also showed “statistically significant and clinically meaningful” reductions on another depression severity scale called CGI-S in both patient populations, the SVB team noted.

Study 403 targeted a large patient population. By Intra-Cellular’s estimates, about a third of patients with either major depression or bipolar depression show mixed features, which is defined by having co-occurring manic or depressive symptoms during a depressive or manic episode. These patients are more severe and more difficult to treat, according to Intra-Cellular Therapies.

Meanwhile, besides the lack of regulatory precedent in mixed features depression, Intra-Cellular’s path is also complicated by a mid-trial protocol change. Study 403 was originally designed to test Caplyta for bipolar depression. But after another trial win, Intra-Cellular amended the study to its current mixed features form and excluded the patients it had initially enrolled.

While Study 403 appears to be a decisive win, industry watchers are still focusing on two ongoing phase 3 trials for Caplyta as adjunctive treatment in major depressive disorder. As one expert told Mizuho, major depression represents a total market that’s about 10 times that of the drug’s existing bipolar disease indication.

Both SVB and Mizuho argued that the mixed features depression trial win bodes well for Caplyta’s major depression studies, which are expected to read out in 2024.

All told, if Intra-Cellular’s expansion plan pans out in all indications, Caplyta could reach peak sales of $4.3 billion, Mizuho figured, including $1.3 billion from a major depressive disorder. Last year, Caplyta tripled sales year over year to $249 million.