What’s Coming Down the Pike: Drug Approvals in the Second Half of ’24

For the drug industry, 2023 turned out to be a banner year for FDA drug approvals with a total of 55. The FDA has approved 21 novel drugs so far this year, including Rezdiffra (resmetirom), the first treatment approved for noncirrhotic nonalcoholic steatohepatitis, and Tryvio (aprocitentan), the first novel antihypertensive in almost 40 years.

Not included in that new drug approval tally are vaccines, such as Moderna’s messenger RNA respiratory syncytial virus vaccine and added indications for drugs that have already passed muster for another use, such as Wegovy’s (semaglutide) new cardiovascular indication.

The second half of 2024 also looks promising for new approvals. Here are some drugs that the FDA might approve before the end of the year.

OX124 for opioid overdose

Swedish pharmaceutical company Orexo AB is developing a high-dose naloxone product for potential use as a nasal rescue medication in opioid overdoses involving potent synthetic opioids, such as fentanyl. According to the Centers for Disease Control and Prevention, approximately 90% of fatal opioid overdoses in the U.S. are caused by synthetic opioids.

The investigational agent called OX124 was designed using Orexo’s proprietary delivery platform, amorphOX, a powder-based technology that allows for rapid absorption and high bioavailability of naloxone. Additionally, OX124 is designed to remain stable at variable temperatures, including freezing temperatures. Narcan (naloxone) nasal spray requires storage at temperatures between 36 F and 77 F and should not be frozen or exposed to temperatures above 104 F.

The company filed a new drug application for OX124 based on results from a pivotal trial in healthy volunteers. The study met its primary end point, demonstrating a significantly faster and higher absorption compared with intramuscular administration of an injectable reference product.

In a separate exploratory study in healthy volunteers, OX124 demonstrated a faster absorption and higher and more sustained blood concentration of naloxone compared with the current market-leading naloxone rescue product.

The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of July 15, 2024. The PDUFA date is the target date for the FDA to finalize the review of submitted applications and indicate whether it will approve the drug.

Alpha-1062 for
Alzheimer’s disease

Biopharmaceutical company Alpha Cognition Inc., based in Vancouver, British Columbia, Canada,is developing Alpha-1062, a new generation acetylcholinesterase inhibitor (AChEI) for the potential treatment of mild to moderate Alzheimer’s disease. Alpha-1062 is a prodrug of galantamine, an AChEI approved to treat mild to moderate dementia due to Alzheimer’s disease.

The investigational drug is designed to bypass acetylcholinesterase binding in the gastrointestinal tract, thereby reducing the risk of gastrointestinal side effects often associated with other AChEIs. The company filed an application for FDA approval of Alpha-1062 based on four studies demonstrating its bioequivalence to galantamine and galantamine ER. A PDUFA target action date is set for July 27, 2024.

Seladelpar for primary biliary cholangitis

Gilead Sciences closed a $4.3 billion deal acquiring biopharmaceutical company CymaBay Therapeutics and its lead investigational drug seladelpar.

Seladelpar is a potential first-in-class, oral, selective peroxisome proliferator-activated receptor delta agonist under development for the treatment of primary biliary cholangitis (PBC) including pruritus. PBC is a rare, chronic, inflammatory liver condition that primarily affects women. The disease is characterized by inflammation and destruction of the bile ducts, reducing bile flow. Impaired bile flow leads to bile acid accumulation in the liver and eventual liver damage. In the pivotal phase 3 RESPONSE trial, seladelpar met primary end points of biochemical response, normalization of alkaline phosphatase at 12 months, and improvement in pruritus at six months.

Prior to the merger with Gilead, the FDA had granted CymaBay Therapeutics priority review status of seladelpar with a PDUFA action date of Aug. 14.

KarXT for schizophrenia

Bristol Myers Squibb recently acquired Karuna Therapeutics and rights to its investigational antipsychotic, KarXT (xanomeline-trospium). The agent has a novel mechanism of action, targeting both M1 and M4 muscarinic receptors. Conventional antipsychotics inhibit dopamine receptors. KarXT has not been associated with side effects, such as movement disorders, increased prolactin levels, weight gain and drowsiness, often reported with
those conventional antipsychotics. The investigational drug is also being studied for use in Alzheimer’s-related psychosis and bipolar disorder.

In a phase 3 trial, KarXT demonstrated significant improvement in positive and negative schizophrenia symptoms compared with a placebo. Bristol Myers Squibb filed for approval of KarXT for treating schizophrenia in adults, and the FDA set a PDUFA action date of Sept. 26.

Acoramidis for rare form of cardiomyopathy

BridgeBio Pharma, based in Palo Alto, California, is developing acoramidis, a small-molecule stabilizer of transthyretin, for the treatment of adults with transthyretin amyloid cardiomyopathy (ATTR-CM), a rare, genetic, chronic heart condition. The disease is potentially fatal and can result in complications such as heart failure.

The phase 3 ATTRibute-CM trial evaluated the safety and efficacy of acoramidis in adults with ATTR-CM. A total of 632 participants were randomly assigned to receive 800 milligrams of acoramidis orally twice daily or a placebo for 30 months. Results from the trial showed an 81% absolute survival rate and 0.29 average annual cardiovascular-
related hospitalization frequency in participants treated with acoramidis. The FDA has assigned a PDUFA action date of Nov. 29.

Rosanna Sutherby, Pharm.D., is an independent medical writer and community pharmacist in High Point, North Carolina.