Key FDA approvals in 2024

Rezdiffra became the first specific treatment for NASH

The FDA approved the first treatment for nonalcoholic steatohepatitis (NASH) on March 14: Madrigal Pharmaceuticals’ Rezdiffra, or resmetirom. NASH is characterized by the buildup of fatty tissue in the liver and is not caused by alcohol use disorder. The disease can cause permanent damage, like scarring, and it is a leading cause of liver transplants in people aged 65 and older. Madrigal’s small-molecule treatment stimulates the thyroid hormone receptor β, which decreases fatty tissue buildup.

Before Rezdiffra, people with NASH did not have specialized treatment options—only recommendations to change things like diet and exercise and the option of a liver transplant if the disease progressed. While Rezdiffra is the first NASH treatment approved in the US, it likely won’t be the last: Galmed Pharmaceuticals’ Aramchol, Inventiva’s lanifibranor, and Cirius Therapeutics’ azemiglitazone are all in late-stage trials.

Duvyzat offered a nonsteroidal treatment for all types of Duchenne muscular dystrophy

Italfarmaco’s Duvyzat (givinostat) got the FDA’s approval on March 21 to treat people aged 6 and older with Duchenne muscular dystrophy (DMD). This is the first nonsteroidal treatment approved in the US for people with all genetic variants of the rare and deadly neurological disorder, which causes muscles to progressively weaken because of a lack of the muscle protein dystrophin. Duvyzat, which is taken orally, inhibits histone deacetylase enzymes and thereby reduces inflammation and muscle loss.

Although other nonsteroidal drugs can treat DMD, most are approved to treat only a small subset of people. Meanwhile, steroids can be used more broadly, but they only slow the disease’s progression. Patient advocates say Duvyzat’s approval is an important step forward for people with DMD.

People with schizophrenia got another treatment option for the first time in 35 years

The FDA approved Cobenfy, formerly known as KarXT, on Sept. 26. This gave people with schizophrenia an alternative to traditional antipsychotics, which are dopamine receptor agonists. Cobenfy is the first new class of antipsychotic approved since clozapine got the green light in 1989.

Cobenfy was developed by Karuna Therapeutics which was bought by Bristol Myers Squibb in March. The treatment is a combination of xanomeline and trospium. Xanomeline is a muscarinic agonist, which engages regulatory paths in the brain that lower dopamine. This indirect action alleviates symptoms and is thought to lessen side effects associated with directly blocking dopamine receptors. Trospium blocks xanomeline’s activity outside the brain to reduce side effects.

Until Cobenfy’s approval, all available antipsychotics antagonized D2 dopamine receptors in the brain. These treatments lower dopamine levels in some people, but they don’t work for everyone, and they can also cause side effects like tremors, stiffness, weight gain, and hyperprolactinemia.

Breast cancer treatment Itovebi inhibits and degrades a mutant of a popular cancer target

Phosphoinositide 3-kinase (PI3K) is a popular cancer target, and mutations in or amplification of the gene that encodes its isoform PI3Kα is often associated with solid tumors. This link is particularly apparent in breast cancer, in which scientists have identified aberrant PI3Kα signaling in 29% of those cancers.

Genentech’s Itovebi (inavolisib) selectively inhibits and degrades mutant PI3Kα. On Oct. 10, the FDA approved Itovebi in combination with palbociclib and fulvestrant to treat people with certain types of breast cancers. The FDA had granted breakthrough therapy designation—which expedites a drug candidate’s review process—to the Itovebi-palbociclib-fulvestrant combination on the basis of Phase 3 clinical trial results that showed a 57% reduction in the risk of disease progression or death compared with people who took palbociclib and fulvestrant.

FDA rejected MDMA amid a turbulent period for Lykos Therapeutics

Not every prospective new treatment had good luck with the FDA this year. The agency rejected Lykos Therapeutics’ application for using methylenedioxymethamphetamine (MDMA) to treat posttraumatic stress disorder on Aug. 9, requesting the company perform another Phase 3 trial.

This decision was just one part of a tough period for Lykos: the journal Psychopharmacology retracted three papers from the company over data integrity problems, failure to disclose conflicts of interest, and unethical conduct. Lykos says the retracted papers were not part of its application.

The company reorganized after the FDA’s decision and laid off 75% of its employees. In October, the company met with the FDA and announced that the “path forward” includes another Phase 3 trial and a possible third-party review of the data therein.