re: ITCI
December 23, 2019 10:56 AM EST
Natalie Grover
Regulatory
Intra-Cellular's checkered developmental path ends in schizophrenia approval, shares skyrocket
It may be almost the end of the year, but the FDA’s stamina for approvals has persevered.
On Monday, Intra-Cellular Therapies secured the regulator’s blessing for its antipsychotic drug, Caplyta, despite two late-stage schizophrenia studies that left much to be desired. But as is custom with most antipsychotics, trials that fall short do not necessarily deter a drug’s path to approval.
Caplyta, known chemically as lumateperone (or ITI-007), is engineered to “selectively and simultaneously” modulate three neurotransmitter systems implicated in a range of mental illnesses: serotonin, dopamine, and glutamate.
Mixed data emerged from the first late-stage study, which compared two doses of the drug to placebo. Only the high dose surpassed the placebo in improving symptoms of schizophrenia.
In the second pivotal trial, two doses of lumateperone were evaluated against placebo as well as an existing antipsychotic, risperidone. Intra-Cellular’s drug performed slightly worse than placebo and significantly worse than risperidone.
But the company blamed a high placebo response — a common occurrence in psychiatric drug development — in certain trial sites as the primary culprit. Investors did not buy what Intra-Cellular was selling though — its stock took a nosedive, evaporating a lion’s share of its market cap. Still, the New York-based biotech kept the faith, hedging its bet on the entirety of data supporting the drug, including a mid-stage trial.
“The FDA approval of ITCI’s Lumateperone this morning reaffirms that the agency is more flexible than average for neuroscience drugs, again setting (a) precedent that the agency will often look at a mixed efficacy package in CNS through a “glass half full lens,” Stifel’s Paul Matteis wrote in a note. “The Lumateperone news offers another example where (the) FDA was willing to accept a large ph2 study as one of two necessary pivotals.”
Intra-Cellular’s shares $ITCI catapulted more than 141% to $30 in Monday morning trading.
Schizophrenia, which affects roughly 1% of the adult US population, is a minefield for drug developers.
Antipsychotic medicines often provide dramatic symptomatic relief for hallucinations and delusions, and improve disorganized thoughts and behavior — but carry an array of vexing side-effects from minor tolerability issues (such as mild sedation) to unpleasant (such as constipation, sexual dysfunction) to painful (such as acute dystonias) to disfiguring (such as weight gain, tardive dyskinesia) to life-threatening (such as myocarditis, agranulocytosis). Experts and guidelines therefore typically recommend choosing drugs based on side effect profiles, which vary considerably, rather than efficacy, which is largely similar.
Intra-Cellular executives highlighted Caplyta’s safety profile in an interview with Endpoints News.
The most common side-effect associated with the drug (and twice the rate of placebo) was somnolence/sedation (24% for Caplyta and 10% for the placebo).
Mark Neumann
“The hallmark, if you will, of the schizophrenia marketplace is this frequency cycling for patients through multiple anti-psychotics either due to relapse of the disease or due to discontinuation of their current antipsychotic because of the safety and tolerability issues that each of the anti-psychotics has some limitation for, ” the company’s chief commercial officer, Mark Neumann, noted.
“Given that, we believe that there is financial opportunity across a range of patients for a product like Caplyta and the clinical data that we have…the label that demonstrates efficacy for the treatment of schizophrenia, with favorable effects with regard to weight metabolic parameters and extrapyramidal (motor control and coordination) symptoms.”
In pooled data from short term studies, mean changes in weight gain, fasting glucose, triglycerides, and total cholesterol were similar between Caplyta and placebo, and the incidence of extrapyramidal symptoms was 6.7% for Caplyta and 6.3% for placebo, the company said.
The company declined to provide details on its pricing plans for Caplyta, which is set for launch in the first quarter of 2020.
“We estimate the annual course of therapy for atypical antipsychotics range between $4-10K to $8-20K (under a dose titration schedule),’ Jefferies’ analysts noted. “Interestingly, caplyta’s label indicates a fixed 42 mg dose, suggesting no dose titration requirement which adds further differentiation over standard of care.”
Wall Street is projecting $500 million in peak schizophrenia sales, they said. “We acknowledge some recent neuro launches have been slow (e.g. ACAD’s Nuplazid, TEVA’s Austedo, ADMS’ Gocovri, ACOR’s Inbrija), but luma’s comparable efficacy but differentiated safety should allow for a modest launch at the very least.”
Intra-Cellular also harbors ambitions in Europe. “We really will, in all likelihood, go into Europe with a partner. And we haven’t solidified all of those plans yet but that’s going to come next,” CEO Sharon Mates told Endpoints.
Investors should not rule out an eventual M&A for Intra-Cellular, given that big pharma has launched 10 of 12 of the last atypical antipsychotics for schizophrenia, Jefferies’ analysts added.
Intra-Cellular is also testing lumateperone in other mental health ailments, including bipolar and depressive disorders.
Stifel’s Matteis, meanwhile, suggested the FDA approval bodes well for other CNS drug developers whose therapies have seen a setback or two. “While the details for each of the following are unique, we believe the news are incrementally positive for Sage Therapeutics, Acadia Pharmaceuticals and Karuna Therapeutics and to an extent Biogen.”
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