FDA ends busy year with three drug rejections

FDA ends busy year with three drug rejections

  03 Jan 2024

The Food and Drug Administration closed out 2023 with rejections of three drugmaker applications for first approval or expanded use, handing Amgen, Zealand Pharma and Merck & Co. complete response letters for medicines to treat cancer, low blood sugar and chronic cough.

The rejections came at the end of a year in which the regulator’s main review office approved 55 new drugs, the most since 59 were approved in 2018, as past years’ investment in biotech startups and dealmaking paid off with products that succeeded in clinical testing. The FDA’s biologics office also cleared 15 medicines.

The complete response letter issued for Amgen’s cancer drug Lumakras starts a regulatory countdown that could see the drug withdrawn in four years if clinical trials are unable to prove the drug is better than chemotherapy or other treatments.

The FDA granted conditional approval to Lumakras, the first drug targeting a KRAS mutation often found in lung cancer, based on remission data from a clinical trial in which the drug wasn’t compared to a placebo or another medicine.

Companies gaining accelerated approval are supposed to confirm their drugs’ effectiveness with such a comparative trial. But in Amgen’s CodeBreak 200 trial patient, dropouts in the chemotherapy arm and a small survival benefit prompted FDA expert advisers to vote against full approval.

In issuing the complete response letter, the FDA set a requirement for Amgen to complete a confirmatory trial no later than February 2028.

Zealand’s drug, called dasiglucagon, is intended for people with elevated blood sugar due to congenital hyperinsulinism, a condition caused by a mutation that leads the pancreas to secrete too much insulin. The FDA rejected the drug based on deficiencies found during an inspection at a third-party manufacturer, not because of efficacy or safety data in the application, Zealand said.

The company expects to resubmit the application, which allows for up to three weeks of dosing of dasiglucagon, in the first half of 2024 should the manufacturing facility pass inspection. Zealand also plans on seeking approval for dosing beyond three weeks.

The Dec. 20 rejection of Merck’s gefipixant in refractory or unexplained chronic cough was based on FDA’s view that the drug’s clinical trials didn’t demonstrate “substantial evidence of effectiveness.” The regulator didn’t raise any questions about the drug’s safety.

The 55 new medicines the FDA’s main office approved in 2023 easily surpassed the total of 37 it cleared in 2022. They included an antibody drug to treat Alzheimer’s disease, a new type of drug to treat hot flashes from menopause, the second medicine in two years for amyotrophic lateral sclerosis, two dual-acting antibody drugs for multiple myeloma and an antibody to prevent respiratory syncytial virus in babies.

The FDA’s biologics office, meanwhile, cleared the first vaccines for respiratory syncytial virus, the world’s first CRIPSR medicine and several other gene therapies.

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