Psychiatry Month in Review: April 2024

Following a slow month of advancement in the psychiatry pipeline, April showers positive phase 3 data and approvals from the US Food and Drug Administration (FDA).

This month in review captures the top headlines in psychiatry, all the way from the approvals of iloperidone for acute treatment of bipolar I disorder to the promising data on KarXT and brilaroxazine in the pivotal trials of EMERGENT and RECOVER, respectively. Both drugs provide unique mechanisms which can be a game-changer for schizophrenia treatment. The month in review also features a piece on the misconceptions of Autism to feature for national autism awareness month.

FDA News to Know

FDA Approves Iloperidone (Fanapt) for Acute Treatment of Bipolar I Disorder

Vanda Pharmaceuticals announced on April 2, 2024, the FDA approved iloperidone (Fanapt) for the acute treatment of bipolar I disorder. The decision was based on the findings of a phase 3, randomized, double-blind, placebo-controlled study, which found iloperidone demonstrated significant improvement compared to placebo at week 4 for the primary and secondary endpoints, as well as had a comparable tolerability and safety profile to other clinical trials.

Despite the previous controversy of iloperidone for schizophrenia, iloperidone for bipolar disorder demonstrated significant improvements in the Young Mania Rating Scale (P = .000008). Investigators observed significant differences between iloperidone and placebo by day 28.

FDA Approves Over-the-Counter Naloxone Nasal Spray for Opioid Overdose

The FDA approved the over-the-counter naloxone hydrochloride (Naloxone HCI) nasal spray for emergency treatment of an opioid overdose, announced by Amneal Pharmaceuticals on April 24, 2024. The approval followed an Abbreviated New Drug Application (ANDA0 for naloxone hydrochloride (Naloxone HCI) nasal spray at 4 mg.

Naoloxone HCI is the generic, more affordable equivalent to the Narcan HCI Nasal Spray 4 mg, approved in March 2023. Both Narcan HCI Nasal and Naloxone HCI are used to treat drug overdose from opioids, such as heroin, fentanyl, and prescription opioid medications. The Narcan HCI Nasal spray was also approved for nonprescription, over-the-counter use.

FDA Issues a CRL for Ketamine’s Abbreviated New Drug Application

PharmaTher announced on April 18 the FDA issued a Complete Response Letter (CRL) for Ketamine’s Priority Original Abbreviated New Drug Application (ANDA). The letter stated the same quality deficiencies as the FDA review letter PharmaTher received on February 12, 2024, but not any new deficiencies.

The ANDA intended to increase access to ketamine, a drug used to treat pain, mental health, anesthesia, sedation, and neurological indications. With limited ketamine on the market, people may turn to compounded ketamine for mental health issues. However, this ketamine form is not approved by the FDA for psychiatric disorders and thus can pose risks.

Pivotal Data in the Pipeline

KarXT Effective in Improving Schizophrenia Symptoms at 52 Weeks

Xanomeline-trospium (KarXT) significantly improved ≥ 30% of schizophrenia symptoms in ≥ 75 participants, Bristol Myers Squibb announced on Friday, April 6, 2024. The data came from the phase 3 EMERGENT-4 open-label extension trial assessing the long-term efficacy, safety, and tolerability of xanomeline-trospium, an investigational muscarinic antipsychotic that acts as a dual M1/M4 muscarinic acetylcholine receptor agonist in the central nervous system, in adults with schizophrenia. The drug stands apart from other schizophrenia drugs in development or on the market as it does not directly block dopamine receptors.

“This particular compound of KarXT is unique and is potentially really differentiated from the others,” investigator Rishi Kakar, MD, from Segal Trials, told HCPLive back in December.

Check out this recent interview regarding the new KarXT data: Insight on the Promising 52-Week KarXT Data with Rishi Kakar, MD

Phase 3 Data on Brilaroxazine for Schizophrenia with Larry Ereshefsky, PharmD

A new phase 3 study found brilaroxazine at 50 mg and 15 mg significantly reduced symptoms of acute schizophrenia. Investigators from Reviva Pharmaceuticals conducted RECOVER, a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the safety and efficacy of brilaroxazine in patients with acute schizophrenia for 28 days. Participants on brilaroxazine 50 mg had a 10.1-point reduction compared to placebo (P < .001) and significant reductions in positive, negative, and negative marder systems, PANSS social cognition, excitement/agitation, and CGI-s. The drug also helps control inflammatory cytokines.

In an interview with HCPLive, Larry Ereshefsky, PharmD, chief scientific officer at CenExcel Research and Follow the Molecule, discussed the positive data.

Read more:

Larry Ereshefsky, PharmD: Brilaroxazine Improves Schizophrenia Symptoms

Advancing Brilaroxazine Research in Schizophrenia with Larry Ereshefsky, PharmD

Spotlighting Autism Awareness Month

All About Autism: Misconceptions, Stigma, Lack of Females in Research

Females are often underrepresented in clinical trials evaluating autism spectrum disorder (ASD). Due to this, people may not realize a girl has autism since they are looking for characteristics males present. ASD manifests differently for females and males, with the language they use and the way they play. Females are also better at camouflaging their disorder, actively doing something that suppresses their neurodiverse behavior and makes them look “typical.” A chief science officer at the Autism Science Foundation shared what it was like to recognize and diagnose autism in her daughter.