Amylyx Pharmaceuticals has reported positive topline results from the pivotal Phase III LUCIDITY study of avexitide, a potential first-in-class GLP-1 receptor antagonist, in post-bariatric hypoglycaemia (PBH), sending shares up nearly 64%.
At week 16, avexitide reduced hypoglycaemic event rates by 55% versus placebo (p<0.001), meeting the primary endpoint and all secondary endpoints with no drug-related serious adverse events or significant weight change. The most common adverse events were diarrhoea and injection-site reactions. Amylyx plans to submit a US New Drug Application (NDA) before year-end, supported by five prior positive early-phase PBH studies and a Breakthrough Therapy Designation (BTD) in the same market.
The result validates the therapeutic potential of GLP-1 antagonism in a rare complication of gastric bypass surgery where patients experience dangerous, unpredictable glucose drops averaging one severe episode per week. Analyst estimates peg the PBH opportunity at USD 1.5 billion or more.
Beyond PBH, Amylyx is developing AMX0318, a longer-acting GLP-1 antagonist discovered with Gubra, targeting a clinical trial application in 2027. The success redirects attention to a previously overlooked branch of the GLP-1 pathway, where only six antagonist assets exist globally, contrasting with the hundreds of agonists crowding the obesity and diabetes fields. MBX Biosciences' imapextide is the only other notable clinical-stage competitor.