Intra-Cellular's push into MDD with its anti-psychotic Caplyta | $ITCI
SUMMARY
Over the past four years, Intra-Cellular Therapies, Inc. (NASDAQ:ITCI) successfully launched Caplyta (lumateperone) to treat schizophrenia and bipolar depression. Net product sales of Caplyta reached $462.2 million in 2023, reflecting 86% growth from 2022. Starting at zero in March 2020, Caplyta sales increased slowly in 2020-21 during the pandemic when the drug was indicated only for schizophrenia. Annual sales in 2021 approximated $20 million. The drug, however, took off when it was indicated for bipolar depression in December 2021.
Intra-Cellular now expects it can introduce Caplyta to treat major depressive disorder (MDD), a much larger market than either schizophrenia or bipolar depression. For Intra-Cellular, the markets appear perfectly structured as three giant steps of growth. Caplyta potentially can reach about 2.6 million patients in schizophrenia, 11 million in bipolar depression and 21 million in MDD. The company likely will face more competition in MDD but Caplyta skeptics also were plentiful prior to the launches in schizophrenia and bipolar depression. Intra-Cellular has strong data to back up an approval in MDD. The company expects results from two phase III trials (501 and 502) will be the final pieces to file a supplemental NDA to indicate Caplyta in MDD.
Key catalysts
Data from phase III Caplyta (lumateperone) study 501 to treat major depressive disorder (MDD)
Data from phase III Caplyta (lumateperone) study 502 to treat major depressive disorder (MDD)
Key catalyst dates
April 2024 (501)
2Q 2024 (502)
Sentiment, MACE Score & The Edge….
SanaCurrents assigns a 66.3% overall probability Intra-Cellular will report positive data from the MDD trials.
Researchers attribute Caplyta’s success in schizophrenia and bipolar depression to its ability to act on glutamate receptors in the brain, as well as traditional dopamine and serotonin receptors. Anti-psychotic drugs acting on dopamine and serotonin receptors were introduced about 25-30 years ago but second-generation anti-psychotics continued to tinker with different formulations around the same two receptors. Intra-Cellular’s Caplyta delivered a new approach, which physicians embraced in the last four years. In 2023, about 14,000 new physicians prescribed Caplyta, a 63% increase from 2022. There are only 59,000 psychiatrists in US; 61% now have ordered Caplyta. In addition, total prescription growth was 85% during 2023, all from scrips for schizophrenia or bipolar depression.
With 61% of psychiatrists familiar with Caplyta, introducing the drug to the MDD market of 21 million patients should not require extensive education about Caplyta. One analyst forecast calls for peak Caplyta sales of $4.3 billion, with $1.3 billion of the total in MDD sales. Moreover, Intra-Cellular has the data to back up an MDD launch.
The company’s stock climbed 44% in late March 2023 when Intra-Cellular released results from a phase II trial. The company said Study 403 evaluating (Caplyta) lumateperone at a 42mg dose as monotherapy to treat MDD episodes in MDD patients with mixed features, and in patients with bipolar depression with mixed features, met the primary endpoint of symptom reduction on the Montgomery Asberg Depression Rating Scale (MADRS).
The combined (MADRS) point reduction versus placebo in MDD patients with mixed features and in patients with bipolar depression with mixed features was 5.7 (p<0.0001). In the MDD cohort only, the MADRS point reduction was 5.9 (p<0.0001).
To bolster the case for Caplyta in MDD, studies 501 and 502 each are enrolling MDD adult patients who are experiencing an inadequate response to current antidepressant monotherapy (ADT). Approximately 470 patients in each trial are randomized 1:1 to receive lumateperone or placebo, plus ADT. The primary endpoint is the change in MADRS score versus placebo at week 6.
THE EDGE
About two out of three MDD patients fail to achieve remission with first-line treatment, according to the National Institute of Mental Health. While MDD has proven to be a graveyard for companies and drugs previously, Caplyta has the edge of demonstrating success in two prior indications. No sNDA is a slam dunk when seeking approval for a new indication. However, in seeking an sNDA, as Caplyta will, the drug’s safety and manufacturing processes typically do not encounter as much scrutiny as an NDA.
As a result, Intra-Cellular’s bar for Caplyta in MDD is for the phase III trial results to deliver … satisfactorily. The p<0.0001 values in March 2023 from Study 403 more than met that bar, even though Intra-Cellular was using the trials to strengthen the Caplyta franchise, as well as the new indication in MDD.
Patients in Study 403 were randomized 1:1 to receive either lumateperone at 42mg (n=192) or placebo (n=191). Studies 501 and 502 are following the same regimen, except participants will total 470 patients in each trial (sum total of 940 participants) instead of the 383 total in Study 403. More participants in the phase III trials increases the odds for success, signaling Intra-Cellular is likely to report strong data.
Disclosure:
SanaCurrents, the parent of BioCurrents, is initiating coverage and a position in ITCI. SanaCurrents may close its position in ITCI prior to or following the expected catalyst date.