The FDA has recently approved several significant treatments, marking advancements in the management of nonalcoholic steatohepatitis (NASH), Duchenne muscular dystrophy (DMD), schizophrenia, and breast cancer. These approvals address critical unmet needs and offer new hope for patients with these conditions.
First Specific Treatment for NASH
On March 14, the FDA approved Madrigal Pharmaceuticals' Rezdiffra (resmetirom) as the first specific treatment for NASH. NASH is characterized by the buildup of fatty tissue in the liver, leading to potential scarring and liver damage. It is a leading cause of liver transplants in individuals aged 65 and older. Rezdiffra, a small-molecule treatment, stimulates the thyroid hormone receptor β, reducing fatty tissue buildup in the liver. Prior to Rezdiffra, treatment options were limited to lifestyle changes and liver transplantation.
Nonsteroidal Treatment for Duchenne Muscular Dystrophy
Italfarmaco's Duvyzat (givinostat) received FDA approval on March 21 for treating individuals aged 6 and older with DMD. Duvyzat is the first nonsteroidal treatment approved in the US for all genetic variants of DMD, a rare and deadly neurological disorder causing progressive muscle weakening due to a lack of dystrophin. Duvyzat, administered orally, inhibits histone deacetylase enzymes, reducing inflammation and muscle loss. While steroids are used more broadly, they only slow the disease's progression, making Duvyzat a significant advancement.
Novel Schizophrenia Treatment
On September 26, the FDA approved Cobenfy (xanomeline and trospium), formerly known as KarXT, for the treatment of schizophrenia. Developed by Karuna Therapeutics (now part of Bristol Myers Squibb), Cobenfy represents the first new class of antipsychotic medication in 35 years. Cobenfy combines xanomeline, a muscarinic agonist that modulates dopamine pathways, and trospium, which reduces peripheral side effects. Traditional antipsychotics antagonize D2 dopamine receptors, which can cause side effects like tremors, stiffness, weight gain, and hyperprolactinemia. Cobenfy offers an alternative approach by indirectly modulating dopamine levels.
Breast Cancer Treatment Targeting PI3Kα
Genentech's Itovebi (inavolisib) received FDA approval on October 10 for treating certain types of breast cancer in combination with palbociclib and fulvestrant. Itovebi selectively inhibits and degrades mutant PI3Kα, a common cancer target. Mutations or amplification of the PI3Kα gene are frequently observed in solid tumors, particularly in breast cancer, where aberrant PI3Kα signaling is present in approximately 29% of cases. The FDA granted breakthrough therapy designation to the Itovebi-palbociclib-fulvestrant combination based on Phase 3 clinical trial results demonstrating a 57% reduction in the risk of disease progression or death compared to palbociclib and fulvestrant alone.
Setback for MDMA in PTSD Treatment
Lykos Therapeutics faced a setback when the FDA rejected its application for using MDMA to treat posttraumatic stress disorder (PTSD) on August 9, requesting an additional Phase 3 trial. This decision coincided with retractions of three papers from the company in the journal Psychopharmacology due to data integrity issues and ethical concerns. Lykos has since reorganized and is planning another Phase 3 trial.
