With a Phase 3 trial reducing serious and severe hypoglycemic episodes following weight loss surgery, Amylyx Pharmaceuticals plans to file for approval this year. If granted market entry, avexitide could hit peak sales of $1.7 billion worldwide, analysts estimate.
Amylyx Pharmaceuticals’ investigational GLP-1 antagonist reduced moderate and severe hypoglycemic episodes in a Phase 3 study of patients who had undergone gastric bypass surgery, giving the biotech a clear shot at the FDA.
Indeed, Amylyx now plans to file a new drug application for the asset, dubbed avexitide, by year-end, according to a Tuesday morning release.
Although post-bariatric hypoglycemia (PBH) is technically a rare disease, it represents “a huge rare market,” Stifel analysts said in an Aug. 6 note. “[E]ven conservative assumptions support a large blockbuster rare disease opportunity” for avexitide, the firm added, projecting a total addressable market of around 160,000 U.S. patients for the drug and potential peak worldwide sales of $1.7 billion.
Unlike the current GLP-1 giants that mimic the hormone to activate the receptor —including Novo Nordisk’s semaglutide and Eli Lilly’s tirzepatide—Amylyx’s avexitide works in the opposite way. The investigational drug blocks the GLP-1 receptor to suppress the incretin pathway, in turn preventing what the biotech characterizes as the “exaggerated . . . insulin response” in patients with post-bariatric hypoglycemia (PBH).
Data from the Phase 3 LUCIDITY study, revealed Tuesday, support this mechanism of action. At 16 weeks, patients on avexitide met the study’s primary endpoint, demonstrating a 55% reduction in the composite rate of level 2 and level 3 hypoglycemic events—classifications that refer to moderate and severe episodes, respectively. Patients with level 3 hypoglycemia can experience altered mental states due to low sugar levels, according to the Endocrine Society.
Avexitide’s treatment effect was highly statistically significant, according to Amylyx’s analysis. The outcome also appears to exceed the expectations of analysts at Mizuho Securities, who in a Monday note said that LUCIDITY is “powered to detect a 35% treatment effect,” even taking into consideration a high placebo effect.
If avexitide meets the FDA’s bar, it would represent a strong commercial comeback for Amylyx, which in April 2024 pulled its amyotrophic lateral sclerosis (ALS) drug Relyvrio from the market after a failed Phase 3 trial.
Avexitide represents Amylyx’s effort to regain its footing from an otherwise catastrophic setback, as well as the company’s continued dedication to the rare disease market. Aside from avexitide, the biotech is advancing a clutch of other medicines for diseases with high unmet need, including Wolfram syndrome and—refusing to give up on the indication—ALS.
