Amylyx readies approval push after GLP-1 inhibitor halves blood sugar crashes in ph. 3 win

Biotech Amylyx readies approval push after GLP-1 inhibitor halves blood sugar crashes in ph. 3 win By Darren Incorvaia Aug 18, 2026 7:01am Amylyx Pharmaceuticals GLP-1 hypoglycemia endocrine disorders Amylyx Pharmaceuticals’ $35 million bet on the GLP-1 receptor antagonist avexitide appears to have paid off, with the molecule cutting the number of dangerous blood sugar crashes by more than half in patients with a rare endocrine disease. Unlike the approved GLP-1 agonists semaglutide and tirzepatide, avexitide is designed to block the weight loss peptide’s effects rather than mimic it.

In the phase 3 Lucidity trial, 78 patients with post-bariatric hypoglycemia (PBH) were given daily injections of either avexitide or placebo. PBH is a rare complication of gastric bypass surgery, where patients suffer from perilous plunges in blood sugar. This often happens after eating a meal, but not always, Amylyx co-CEO Joshua Cohen told Fierce.

“It can be kind of out of the blue,” Cohen said. “Patients describe it happening when they're stressed or exercising or a number of other things—and their bodies also become very reactive.” Participants in the trial had about one case of drastic blood sugar drop per week, Amylyx’s other co-CEO Justin Klee told Fierce. “Each one of these events—level two or level three hypoglycemic events—is a medical emergency,” Klee explained.

“Every single one.” With no viable treatments available, Klee said that patients are forced to live “small lives,” carefully managing what they eat and what they do. Cohen described patients who only shower when someone else is in the bathroom with them, or who have been in car crashes because of hypoglycemic events while driving. Avexitide reduced the rate of these hypoglycemia events by 55% through Week 16 of the trial compared to placebo, hitting the trial's primary endpoint.

The drug also met all of the trial's secondary endpoints and didn’t lead to any severe side effects or changes in body weight, Amylyx reported, with the most common side effects being diarrhea and injection site reactions. “When we shared the results with the steering committee, they were overjoyed at the results,” Klee said. “They were just so excited about what this will mean for their patients.” Amylyx plans to submit an approval application to the FDA by the end of the year, and has already begun preparing heavily for a commercial launch.

With five previous positive readouts for avexitide in PBH, the Cambridge, Massachusetts-based biopharma has been spending the year readying for its FDA filing in anticipation of Lucidity’s success. “If you have an important medicine or what looks to be a potentially important treatment for people, you have a responsibility to try to deliver it as quickly as you can,” Klee said. Because avexitide already has breakthrough therapy designation, he added, Amylyx anticipates potentially receiving priority review.

Though the company is currently laser-focused on getting avexitide approved in PBH, Cohen said, the company also has its eyes on targeting other surgeries that can alter how the body processes nutrients. “There's many other surgeries people get that can cause a similar effect,” he said, “whether that's gastric surgery for gastric cancers, esophageal surgeries for esophageal cancers [or] Nissen fundoplication, which is a surgery for severe gastric reflux.” One potential avenue for avexitide expansion is in Japan, Cohen added, where gastric cancer is the most common cause of cancer death and many related surgeries occur. The company purchased avexitide from Eiger Biopharma for $35.1 million in the summer of 2024, not long after Amylyx voluntarily pulling its amyotrophic lateral sclerosis drug Relyvrio off the market.

The med was approved in 2022 but later failed a confirmatory phase 3 trial. “When you're pioneering new areas, there can be setbacks,” Klee told Fierce. “The mission has remained the same.

We're very proud that much of the team who was with us during that time is still with us today.” While Relyvrio was ultimately unsuccessful, Amylyx still hasn’t given up on helping patients with ALS. The biopharma is currently testing an antisense oligonucleotide called AMX0114 in a phase 1 trial with ALS patients. AMX0114 targets Calpain-2, an enzyme that is overactive in ALS and contributes to the disease’s devastating neurodegeneration.

Amylyx Pharmaceuticals GLP-1 hypoglycemia endocrine disorders rare diseases Clinical Data Biotech