[Updated 1:33 p.m.] Intra-Cellular Therapies will have to wait another three months to see whether the FDA will approve its experimental drug for schizophrenia, which has produced mixed results in human studies but is currently under a regulatory review.
The New York company said Monday that the FDA has pushed back the deadline for its review of the drug lumateperone until Dec. 27 so the agency can review information from safety studies in animals. Intra-Cellular (NASDAQ: [[ticker:ITCI]]) is confident it can answer the agency’s questions and plans to respond in the coming weeks, CEO Sharon Mates said on a Monday morning conference call with analysts. [Story updated throughout with background on lumateperone and additional analyst comment.]
The news marks the latest twist in Intra-Cellular’s long-running quest to win approval of lumateperone, a drug that the company has been developing for schizophrenia, bipolar depression, and other psychiatric disorders. Intra-Cellular has filed for approval of the drug in schizophrenia despite a mixed clinical track record: Lumateperone succeeded in some placebo-controlled studies in schizophrenia, but failed one as well. The drug also recently came up short in a Phase 2 study in bipolar depression last month. Shortly afterwards, the company revealed that the FDA had cancelled a scheduled July 31 advisory committee meeting for lumateperone, adding more uncertainty to the drug’s future.
Intra-Cellular shares fell more than 30 percent after the disclosure and have yet to recover, but the company said at the time that the agency was looking for more information from “non-clinical studies,” not human tests like the bipolar study. The FDA had made a similar request before: In 2017, the agency flagged worrisome safety signals from a study in dogs, and asked for more data about long-term use of lumateperone. The company was able to convince the FDA that the problems wouldn’t carry over to humans, and it continued with clinical studies.
The issue has resurfaced, but Intra-Cellular still doesn’t expect any problems. On the conference call, Mates said that Intra-Cellular’s tests show that dogs and humans metabolize the drug differently. In dogs, byproducts of metabolism called metabolites are formed, some of which are associated with toxic effects, Mates said. These metabolites are chopped up in pieces and remain in the dog’s body. Human metabolism of the drug produces large, water-soluble molecules that are excreted from the body, Mates added.
Mates declined to elaborate on the nature of the drug’s toxic effects on dogs, other than to say it didn’t cause liver problems. She said metabolites were also observed in rats , but problems were only seen in dogs.
“We believe that the findings in the dogs are not relevant to humans, and therefore, we don’t need to spend our time describing what we see in the dogs,” Mates said.
Mates noted that in 2017, the FDA agreed that Intra-Cellular had provided enough data about the drug’s safety. There are no new findings now, she added. The regulator just wants laboratory data confirming the company’s assessment that the findings are not relevant to humans, Mates said. The company will analyze dog and human plasma samples from earlier studies.
While lumateperone’s future is unclear, RBC Capital markets analyst Brian Abrahams wrote that the update was reassuring in that the FDA’s lumateperone concerns “may be addressable.” The fact that the FDA allowed the company to continue giving lumateperone to patients two years ago could indicate that the regulator is generally comfortable with the drug’s safety profile, he wrote.
“Overall, while some outstanding questions and risk remain,” Abrahams wrote, “lumateperone could still have a path forward in schizophrenia.”
SVB Leerink analyst Marc Goodman said in a research note that the Intra-Cellular drug appears to be “back on track.” Only a small number of lab tests are required, and the company has already started them, he wrote. But he cautioned that there is always risk when the FDA calls for more tests, and “this appears to be the same situation that the investment community thought was resolved two years ago, so it’s clear the issue may be more significant than we had all appreciated.”
Intra-Cellular shares climbed about 5 percent on the news.
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