Policy & Regulation
Otsuka, Lundbeck Announce FDA Acceptance of Supplemental New Drug Application; Receive Priority Review for Treatment of Schizophrenia in Adolescents
18 October 2021 - - The US Food and Drug Administration has accepted a Supplemental New Drug Application for the treatment of schizophrenia in adolescents with Rexulti and has granted Japanese pharmaceutical company Otsuka Pharmaceutical Co., Ltd. and Danish pharmaceutical company H. Lundbeck A/S Priority Review, the companies said.

Up to one-third of patients with schizophrenia develop the disease during adolescence.

Currently, Rexulti is approved in the US for treatment of schizophrenia in adults and adjunctive treatment of major depressive disorder in adults.

The submission has been completed one year earlier than planned, with the hope of benefitting adolescent patients with schizophrenia who need more treatment options.

The acceleration of the program was made possible by doing an extrapolation analysis using data from prior studies in adult patients, pharmacokinetic results from adult and pediatric trials, and six-month data from the ongoing open-label, long-term trial in adolescent schizophrenia patients (Trial 331-10-236).

Based on an interim analysis of the ongoing open-label, long-term trial, brexpiprazole appears to be a potential treatment option for adolescent patients with schizophrenia, with a safety profile consistent of that observed in adult patients.

The most common adverse event was somnolence with an incidence of 10.2%, and the incidence of akathisia was 2.4%.

The results of the more than 100 adolescent patients treated for at least 6 months from the trial will be presented at the Psych Congress taking place October 29 to November 1, 2021, and is intended to be published in a peer-reviewed scientific journal during 2022.

The FDA is expected to complete its review of the sNDA by December 2021.

The current global pediatric clinical program includes two completed phase 1 trials and two ongoing phase 3 trials.

The two completed phase 1 trials investigated the PK, safety, and tolerability of brexpiprazole.
The pharmacokinetic extrapolation was done using data from the two pediatric phase 1 trials together with data from three adult phase 1 trials to build a model that assesses whether the blood concentration of brexpiprazole was similar in adolescents compared to that in adults.

Two phase 3 trials are currently underway in adolescents (13-17 years old) with schizophrenia to evaluate short-term efficacy and safety (Trial 331-10-234) and long-term safety and tolerability (Trial 331-10-236) of brexpiprazole as part of the initial agreement on the pediatric program with both FDA and the European Medicines Agency.

Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action for brexpiprazole is not fully understood.

However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.

Brexpiprazole exhibits high affinity (sub-nanomolar) for these receptors as well as for noradrenaline alpha1B/2C receptors.

Depending on the market, brexpiprazole is known as Rexulti or Rxulti.


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