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Sage's Zulresso (brexanolone) nears US approval for postnatal depression after a positive FDA vote, potentially becoming the first PPD-specific drug. Alkermes' ALKS 5461 faces rejection for treatment-resistant MDD due to efficacy concerns. Sage also explores brexanolone for bipolar disorder and advances SAGE-217 for MDD.

James Mannion, incarcerated in Maine, died from an opioid overdose after being denied buprenorphine, a medication for opioid use disorder. His death highlights the U.S. criminal justice system's widespread resistance to addiction medications like buprenorphine and methadone, despite their proven effectiveness in reducing overdose deaths and recidivism. Many jails and prisons do not offer these medications, perpetuating a cycle of addiction and incarceration. Legal actions and changing attitudes among law enforcement suggest a slow shift towards recognizing the importance of these treatments.

Dr. Horan, Dr. Sauder, Dr. Ramsay, and Dr. Yohn are Bristol Myers Squibb employees. Dr. Harvey has affiliations with multiple companies, including Bristol Myers Squibb. Dr. Ramsay holds Bristol Myers Squibb stock. Dr. Keefe consults for various companies and has received royalties. Dr. Davis consults for several companies. Dr. Paul has roles at Karuna Therapeutics, Sage Therapeutics, and Voyager Therapeutics. Dr. Brannan was with Karuna Therapeutics and now consults for Bristol Myers Squibb.

OLZ/SAM (Lybalvi) maintained symptom control over 4 years in patients with schizophrenia, schizophreniform disorder, or bipolar I disorder, with lower weight gain and fewer AEs compared to olanzapine alone.

Axsome Therapeutics' AXS-12 met primary endpoint in Phase III ENCORE trial, reducing cataplexy attacks by 72% at one month and 82% at six months. The company plans to submit an NDA to the FDA.

Hal Pyzyna, who relapsed during the COVID-19 pandemic, died from a drug overdose after being pressured to take Vivitrol at Crown Recovery Center. His mother, Kristine Pyzyna, believes Vivitrol and improper administration at ARC contributed to his death and seeks stricter oversight. ARC, Kentucky's largest treatment provider, faces an FBI investigation and staff cuts, but maintains commitment to quality care.

K.W. is a member of the ACTIVE Workgroup supported by Alkermes, Dicerna, Ethypharm, Lundbeck, Mitsubishi, and Otsuka. J.L.M., B.P.L., and M.C.M. are consultants for GlaxoSmithKline, Novo Nordisk, HepaTX, and Prodigy. M.C.M. also serves on the Board of Amygdala Neuroscience and receives research support from Durect. Other authors declare no competing interests.

The Inflation Reduction Act (IRA), effective 2026, aims to reduce Medicare spending by $6 billion in 2026, sparking debate over its impact on drug innovation and availability. It targets high-spending Medicare drugs, potentially reducing small molecule development and affecting therapeutic areas like oncology and endocrinology. Industry reactions are mixed, with some companies adjusting strategies in response. The IRA's long-term effects on innovation and patient access remain uncertain.

Centessa's ORX750, an OX2R agonist, showed significant wakefulness improvements in a phase 1 trial, with the 2.5 mg dose restoring normal wakefulness. ORX750 was safe and well-tolerated, prompting plans for phase 2 trials in narcolepsy types 1 and 2, and idiopathic hypersomnia starting late 2024.

Centessa Pharmaceuticals plans to rapidly advance its experimental drug after a small study showed significant increase in time to sleep in healthy volunteers. The company intends to start mid-stage studies by year-end, evaluating the drug against narcolepsy and idiopathic hypersomnia. Centessa's CEO, Saurabh Saha, noted the data exceeded expectations, leading to accelerated development. The drug targets orexin proteins, with potential for a 1 mg, once-daily treatment, comparing favorably to Takeda's candidate. The study used Maintenance of Wakefulness Tests, showing the drug restored normative wakefulness with favorable safety and tolerability.