Lumateperone (Caplyta) - ITCI’s Undervalued Mental Health Drug?
Bipolar disorder includes type 1 (BD-1) and type 2 (BD-II), and affects 1-4% of the population (2). Treatment of depression associated with bipolar disease (bipolar depression) remains unsatisfactory but includes some antipsychotics such as lurasidone and quetiapine (1, 2). Some other widely prescribed drugs for treating bipolar disorder include valproate and especially lithium (1, 2). All of these have unfavorable side effect profiles (See Table 1). Another concern with lithium is toxicity, which requires careful monitoring/dosing and kidney function monitoring (3). Furthermore, lithium has drug interactions that need to be taken into account (3). Thus, there remains a need for effective drugs with better safety profiles in bipolar depression
ITCI has a promising clinical drug candidate in late-stage development that may bring us a treatment option for treating bipolar depression with a more favorable safety profile. ITCI recently released data on lumateperone (Caplyta) as adjunctive therapy to valproate or lithium for the treatment of depression in BD-I and BD-II patients (Study 402). This trial met its primary and major secondary endpoints with impressive results (Study 402).
The major side effects of Lumateperone observed in this trial, similar to those on the label of its marketed version for schizophrenia, Caplyta, were somnolence, dizziness, and nausea. Overall, lumateperone (Caplyta) has a side effect (i.e. adverse event) profile that seems less severe than other treatment options for bipolar depression (See Table 1). For example, although lumateperone appears to share a high degree of somnolence with other anti-depressants used to treat bipolar depression, it does not have the prevalence of agitation, headache, extrapyramidal symptoms, and other issues seen with the current drugs used to treat bipolar depression. Of course, when combined with lithium and valproate, as in the most recent trial, the side effects that correspond to those drugs still occur as well. It is noteworthy that the black box label of ITCI’s Caplyta does not have the “SUICIDAL THOUGHTS AND BEHAVIORS” language found on the labels of antipsychotics like quetiapine and lurasidone (See Table 1).
This most recent trial provides additional data to support the safety and efficacy of lumateperone in BD-I and BD-II. In a prior lumateperone trial (Study 404), the drug candidate was used alone vs placebo and demonstrated significant single-agent activity for both BD-I and BD-II patients (Study 404). However, as is common in CNS drug development, the clinical trial history of lumateperone in BD is not entirely positive. Another trial (Study 401) that ITCI conducted for lumateperone vs. placebo in bipolar depression did not meet its major primary and key objective secondary endpoints (Study 401). All of the prior trial data can be found in our AmpCard for lumateperone in BD (Amp Card).
With its mixed clinical trial history, will lumateperone obtain FDA approval for the lumateperone sNDA for treating depression in bipolar disorder? We think the chances of lumateperone being approved for the treatment of bipolar depression is good, similar to lumateperone in schizophrenia where there were two positive and one negative trial (4). However, there is an ongoing confirmatory trial in bipolar depression, and it is possible that the FDA conditionally approves the sNDA pending positive results for that study.
In addition to the question about FDA approval, there is an ongoing question currently of whether lumateperone’s disappointing sales to date are not only because it is being launched during the COVID pandemic, or whether there are other factors. The lumateperone (Caplyta) schizophrenia launch is the first drug launched by ITCI’s commercial organization and it is possible that this newly formed organization is not set up to operate effectively. However, with lumateperone’s favorable safety profile and adequate efficacy data, it is likely that ITCI will be able to grow its revenue substantially in the coming quarters/years, especially of course if it can get the bipolar depression indication sNDA approved. Although there are generic options, these are very large markets. For example, for schizophrenia alone, the U.S. market in 2007 was $12 billion (5). Peak sales of drugs in these markets typically are $100s of millions and many times in the billions (See table 1). Given lumateperone’s properties, clinical status, and the size of the markets for schizophrenia and bipolar depression, it seems that ITCI would be an attractive M&A target for a large cap pharma with a commercial team already in place that targets these markets.
What do you think, is ITCI undervalued given the promise of lumateperone? Will the drug get to $500M of sales or even $1 billion at its peak?
Written by Maggie @Ampbioresearch, Reviewed by Manny @Ampbioresearch
Cites:
Pharmacological treatment of adult bipolar disorder | Molecular Psychiatry
Lithium Prescribing and Monitoring in Clinical Practice - A Primer
#ITCI #Caplyta #Lumateperone #Bipolardepression #schizophrenia