July in Review: Updates on the Psychiatric Treatment Pipeline

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Take a look at this month’s developments in the psychiatric treatment pipeline. We compiled a recap of the latest news here, just in case you missed any of the updates.

FDA Requires New Label Warning of Weight Loss Risk in Pediatric Patients Taking Extended-Release Stimulants for ADHD

The US Food and Drug Administration (FDA) announced it has revised the label of all extended-release stimulants indicated to treat attention-deficit/hyperactivity disorder (ADHD), including certain formulations of amphetamine and methylphenidate, to warn about the risk of weight loss and other adverse effects in patients younger than 6 years of age. According to analysis of data from clinical trials of extended-release formulations of amphetamine and methylphenidate for ADHD treatment, patients younger than 6 years have higher plasma exposures and higher rates of adverse effects than older children taking the same medication at the same dosage.

Positive Results From the Phase 2b Study of BPL-003 in Patients With Treatment-Resistant Depression

In the largest controlled clinical study to investigate mebufotenin and the only blinded phase 2b study of mebufotenin to include the United States, BPL-003in patients with treatment-resistant depression demonstrated rapid, robust, and durable antidepressant effects with a single dose. For the primary endpoint, at day 29, a single 12 mg dose of BPL-003 demonstrated a statistically significant reduction in depressive symptoms, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), with a mean decrease of 11.1 points from baseline compared with a 5.8 point reduction in the 0.3 mg comparator group (P = 0.0038). For the key secondary endpoints, a single 8 mg dose of BPL-003 also showed significant improvement at day 29, with a mean MADRS score reduction of 12.1 points (P=0.0025 for change vs 0.3 mg control). Investigators noted that both the 8 mg and 12 mg doses of BPL-003 showed statistically significant improvements in MADRS scores as early as a single day after dosing and maintained effects until week 8.

sNDA Submitted: Lumateperone for the Prevention of Relapse in Schizophrenia

Johnson & Johnson submitted a supplemental New Drug Application (sNDA) to the FDA based upon long-term data evaluating the safety and efficacy of lumateperone (Caplyta) for the prevention of relapse in schizophrenia. Caplyta 42 mg is an oral, once daily atypical antipsychotic approved for the treatment of adults with schizophrenia and depressive episodes associated with bipolar depression, as both monotherapy and as adjunctive therapy with lithium or valproate. Caplyta significantly reduces schizophrenia relapse risk, with a 63% reduction compared with placebo in a phase 3 trial.

TSND-201 Receives Breakthrough Therapy Designation From FDA for PTSD

The FDA granted Transcend Therapeutics with the Breakthrough Therapy designation for their compound TSND-201 for (methylone) for the treatment of posttraumatic stress disorder (PTSD) following positive results from its IMPACT-1 study. TSND-201 showed significant efficacy in reducing PTSD symptoms, with improvements seen as early as Day 10 and sustained through Day 64.

First Patient Dosed in Phase 2b Study of GlyphAllo for Patients With Major Depressive Disorder, With or Without Anxious Stress

The first patient has been dosed in the phase 2b BUOY-1 study of GlyphAllo (Glyph Allopregnanolone, or SPT-300) in major depressive disorder (MDD) with or without anxious distress. If successful, GlyphAllo could be a first-in-class treatment for patients with MDD, with or without anxious distress. GlyphAllo is a novel oral prodrug of allopregnanolone, designed to overcome previous clinical use limitations.

FDA Advisory Committee Votes Against Recommending Brexpiprazole Plus Sertraline for PTSD

The FDA Advisory Committee voted not to recommend brexpiprazole (Rexulti) in combination with sertraline for posttraumatic stress disorder (PTSD). The panel believed the efficacy was not well-enough established to recommend its approval. The vote was 10-1. The discussion attempted to balance the disappointment in the phase 3 results with the potential hope this treatment could offer. Discussion participants cited “confusing, contradictory datasets” and “discordant results."

Potential Label Expansion for Igalmi: Pre-Supplemental New Drug Application Meeting Package Submitted

BioXcel Therapeutics has submitted a pre-supplemental New Drug Application (pre-sNDA) meeting package to the FDA for Igalmi in support of a potential label expansion for outpatient use for the acute treatment of agitation associated with bipolar disorders or schizophrenia. Igalmi is an investigational, orally dissolving film formulation of dexmedetomidine, a selective alpha-2 adrenergic receptor agonist. Igalmi is the first and only FDA-approved orally dissolving sublingual film for mild, moderate, or severe agitation in patients with schizophrenia or bipolar I or II disorder, administered under the supervision of a health care provider.

Positive Phase 2 Data: Alixorexton for the Treatment of Adults With Narcolepsy Type 1

Alkermes announced positive topline results from the randomized double-blind treatment period of the Vibrance-1 phase 2 study evaluating alixorexton in patients with narcolepsy type 1 (NT1). Treatment with alixorexton led to statistically significant and dose-dependent improvements in sleep latency among patients with NT1. Alixorexton, formerly referred to as ALKS 2680, is a novel, investigational, oral orexin 2 receptor agonist in phase 2 development as a once-daily treatment for NT1, narcolepsy type 2, and idiopathic hypersomnia. Alixorexton met the primary endpoint across all doses tested, demonstrating statistically significant, clinically meaningful, and dose-dependent improvements from baseline compared with placebo in wakefulness.

Positive Topline Results From Phase 3 Trial of AD109, First Oral Pill for Obstructive Sleep Apnea

Apnimed announced positive topline results from the LunAIRo study, its second pivotal phase 3 clinical trial of their lead candidate, AD109 (aroxybutynin 2.5 mg/atomoxetine 75 mg) for obstructive sleep apnea (OSA). AD109 is a first-in-class, anti-apneic neuromuscular modulator that targets the root cause of OSA by increasing upper airway muscle tone during sleep. It is designed to be a once-daily pill taken at bedtime. Participants treated with AD109 achieved clinically meaningful and statistically significant reductions in airway obstruction at 26 weeks. AD109 also demonstrated improvements in additional topline secondary and exploratory endpoints in the LunAIRo study, such as meaningful improvements in oxygenation as assessed by reductions in hypoxic burden (P<0.0001) and oxygen desaturation index (P<0.001) at week 26 and at end of study (week 51).

New Insights on Alzheimer Disease Treatments and Diagnostic Tools: Trontinemab and the Elecsys pTau217

According to data presented at the Alzheimer’s Association International Conference (AAIC) in Toronto, Canada, trontinemab demonstrated significant amyloid plaque reduction and a favorable safety profile in the phase 1b/2a Brainshuttle AD study. Phase 3 TRONTIER studies will evaluate trontinemab's efficacy in early symptomatic AD, focusing on cognitive and functional outcomes. Additionally, the Elecsys pTau217 blood test, comparable with PET scans, received FDA Breakthrough Device Designation, enhancing AD diagnostic accessibility.

Cingulate Receives $4.3 Million PDUFA Fee Waiver for ADHD Treatment, CTx-1301

Cingulate announced that it has received a fiscal year 2025 Prescription Drug User Fee Act (PDUFA) fee waiver from the US Food and Drug Administration (FDA) for its new drug application (NDA) for dexmethylphenidate HCI (CTx-1301) for the treatment of ADHD in patients aged 6 years and older. The waiver, granted through the small business waiver provision of the Federal Food, Drug, and Cosmetic Act, will save Cingulate approximately $4.3 million as it prepares to submit its NDA at the end of this month. CTx-1301 is a novel, investigational, trimodal, extended-release tablet formulation of dexmethylphenidate and Cingulate’s lead candidate.

New Data: Zervimesine for the Treatment of Dementia With Lewy Bodies and Alzheimer Disease

Investigators presented data at the Alzheimer’s Association International Conference (AAIC) in Toronto, Canada on zervimesine (CT1812). Zervimesine showed safety and efficacy in dementia with Lewy bodies, improving neuropsychiatric symptoms by 86% compared with placebo in the SHIMMER study. The SHINE study revealed zervimesine halted cognitive decline in Alzheimer patients, especially those with lower p-tau217 levels, indicating a potential biomarker for treatment response. Research posters highlighted zervimesine's impact on neuroinflammation and synapse health, suggesting its potential to modify Alzheimer disease biology.

FDA Clearance of IND for Ketamir-2, Novel Oral NMDA Receptor Antagonist for Neuropathic Pain

MIRA Pharmaceuticals announced that the FDA cleared its Investigational New Drug (IND) application for Ketamir-2, a novel oral NMDA receptor antagonist for the treatment of neuropathic pain. The IND application for Ketamir-2 includes comprehensive preclinical data, demonstrating no neurotoxicity and potent analgesic effects. Ketamir-2 showed superior efficacy and safety in preclinical neuropathic pain models compared to gabapentin and pregabalin. Ongoing phase 1 trials are nearing completion, with plans for a phase 2a study in diabetic peripheral neuropathy and potential trials for chemotherapy-induced neuropathy.

Positive Phase 2b/3 Open-Label Extension Trial Results: Blarcamesine for Treatment of Early Alzheimer Disease

Anavex Life Sciences shared promising results from a phase 2b/3 open-label extension trial of extended oral blarcamesine for the treatment of early Alzheimer disease (AD) at the 2025 Alzheimer's Association International Conference (AAIC) in Toronto. Blarcamesine demonstrated significant cognitive (ADAS-Cog13: -5.43, P=0.0035) and functional (ADCS-ADL: +9.50, P<0.0001) improvements in patients with early AD. The trial demonstrated up to 84.6 weeks (19.5 months) of 'time saved' in disease progression for patients who started treatment early.

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