Med Check: FDA Breakthrough Status for Schizophrenia Drug, Review of Oral Film for Agitation, and More

In May the Food and Drug Administration (FDA) granted Breakthrough Therapy designation for BI 425809, Boehringer Ingelheim’s investigational oral glycine transporter-1 inhibitor, for the treatment of cognitive impairment associated with schizophrenia. The FDA’s Breakthrough Therapy designation expedites the development and review of drugs for serious conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that indicate that the drug may demonstrate substantial improvement over available therapy on at least one clinically significant endpoint.

The FDA granted Breakthrough Therapy designation based on the results of a phase 2 clinical trial that demonstrated that BI 425809 improved cognition in adult patients with schizophrenia. In the study, patients with schizophrenia in 11 countries were randomized to receive either 2 mg to 25 mg of BI 425809 or placebo daily for 12 weeks. All patients were medically stable with no hospitalization for worsening of schizophrenia in the three months before randomization. They were also psychiatrically stable with no exacerbations in their symptoms in the three months before randomization.

At 12 weeks, cognitive function improved in patients who took BI 425809, as measured by the composite Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. This series of tests assesses patients’ speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Boehringer Ingelheim also announced the planned initiation of a phase 3 trial to assess the safety and efficacy of BI 425809 for improving cognition in adults with schizophrenia.

BioXcel Therapeutics in May announced that the FDA has accepted for review BXCL501 (dexmedetomidine oral film) for the acute treatment of agitation associated with schizophrenia and bipolar disorders I and II.

The FDA accepted the company’s new drug application based on the results of two phase 3 clinical trials. Patients in both trials received either BXCL501 (120 mcg or 180 mcg) or placebo while they were experiencing agitation as measured via the Positive and Negative Syndrome Scale, Excitatory Component (PEC). SERENITY I included 381 patients with schizophrenia, and SERENITY II included 378 patients with bipolar disorder.

In both trials, patients who received BXCL501 had greater improvements in PEC scores at two hours compared with those who received placebo. Patients with schizophrenia who received the 180 mcg dose showed improvements in PEC scores as early as 20 minutes after treatment; similar rapid improvements were seen in patients with bipolar disorder who received either dose of the medication.

In May U.S. Marshals seized more than 207,000 units of dietary supplements and bulk dietary ingredients containing kratom, including more than 34,000 kilograms of bulk kratom. The seizure was carried out at the FDA’s request. The dietary supplements are manufactured by Atofil LLC and are marketed under the brand names Boosted Kratom, The Devil’s Kratom, Terra Kratom, Sembuh, Bio Botanical, and El Diablo. Kratom is a plant touted as a “natural opiate,” but there are currently no FDA-approved uses for it.

Although kratom is legal in much of the nation, the U.S. Department of Justice, on behalf of the FDA, filed a complaint in the U.S. District Court for the Middle District of Florida alleging that kratom is a new dietary ingredient for which there is inadequate information to provide reasonable assurance that it is not harmful. The complaint stated that dietary supplements and bulk dietary ingredients that are, or contain, kratom are adulterated under the Federal Food, Drug, and Cosmetic Act.

“There is substantial concern regarding the safety of kratom, the risk it may pose to public health, and its potential for abuse,” said Judy McMeekin, Pharm.D., the FDA’s Associate Commissioner for Regulatory Affairs in a statement.

The agency noted that taking kratom can cause respiratory depression, vomiting, nervousness, weight loss, and constipation. The agency added that kratom has both narcotic and stimulant effects, and that withdrawal symptoms may include hostility, aggression, excessive tearing, aching muscles and bones, and jerky limb movements.

The FDA will review Caplyta (lumateperone) for the treatment of depressive episodes associated with bipolar I or II disorder, Intra-Cellular Therapies announced in May. Caplyta is currently approved for the treatment of schizophrenia in adults.

The FDA accepted the company’s supplemental new drug application based on findings from two phase 3, placebo-controlled trials of the drug in people with bipolar depression, Study 404 and Study 402.

Study 404 evaluated lumateperone as a monotherapy in the treatment of major depressive episodes associated with bipolar disorders I and II. In the study, 381 patients were assigned to receive 42 mg lumateperone or placebo once a day for six weeks. At the end of the trial, symptoms of depression decreased in patients who took lumateperone compared with those who took placebo, as measured by a change in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Study 402 evaluated lumateperone as an adjunctive therapy to lithium or valproate in the treatment of major depressive episodes associated with bipolar disorders I and II. In the study, 529 patients were randomly assigned to receive 28 mg or 42 mg of lumateperone or placebo once a day for six weeks. The patients also took either lithium or valproate as mood stabilizers. At the end of the trial, symptoms of depression decreased in both groups of patients compared with those who took placebo. ■