Amylyx Advances Avexitide for Post-Bariatric Hypoglycemia with Q3 2026 Data Expected

Amylyx Pharmaceuticals executives told investors the company entered 2026 with a focus on advancing avexitide toward what could become the first FDA-approved therapy for post-bariatric hypoglycemia (PBH), while continuing early-stage work across its pipeline and maintaining a cash runway management said extends into 2028.

The co-CEO said the company's "top priority" is advancing avexitide, a GLP-1 receptor antagonist, in PBH. Management outlined three 2026 objectives: delivering top-line data from the Phase 3 LUCIDITY trial in Q3 2026, advancing NDA readiness, and strengthening launch readiness for a potential 2027 commercialization if approved.

The Chief Medical Officer described PBH as a chronic condition driven by an exaggerated GLP-1 response after food intake that can lead to recurrent hypoglycemia and neuroglycopenia, with potential consequences including cognitive dysfunction, seizures, and loss of consciousness. She emphasized that there are currently no FDA-approved therapies for PBH.

LUCIDITY is evaluating avexitide 90 mg once daily in individuals with PBH following Roux-en-Y gastric bypass surgery. The trial uses an FDA-agreed primary outcome: a reduction in the composite of level 2 and level 3 hypoglycemic events through week 16.

LUCIDITY was designed for replication based on five prior PBH trials with avexitide, which management said demonstrated statistically significant reductions in hypoglycemic events. A prior result showed avexitide 90 mg once daily led to a 64% least squares mean reduction versus baseline in the composite rate of level 2 and level 3 events (p=0.0031), and a Phase 2 trial showed no placebo response. Despite that, the company modeled up to a 50% placebo effect and a 35% effect size versus placebo in its Phase 3 assumptions, which was intended to be conservative and keep the study well powered.

The recruitment phase of LUCIDITY is complete and the company expects to "fully complete enrollment this quarter," with the final potential patients in screening and the last eligible participants expected to be randomized and dosed this month.

The trial's open-label extension (OLE) is underway and participants may enter the OLE immediately upon completion of the double-blind phase. Management said the company does not report details of an ongoing study, but added that management was pleased with participation and that participants are rolling over into the extension.

Management emphasized that LUCIDITY's inclusion criteria and design were informed by prior successful Phase 2 studies. Executives said discussions with sites have reinforced the severity and unmet need in PBH, describing hypoglycemic events as medical emergencies and highlighting physicians' limited tools beyond medical nutrition therapy.

Participants receive training and are asked to reaffirm adherence to dietary guidelines intended to maintain consistency in medical nutrition therapy throughout the study. Management added it did not expect a waning drug effect and said avexitide's safety profile has been "very good" across clinical and non-clinical studies.

Alongside clinical execution, management discussed ongoing commercial and medical affairs buildout. The company is making key hires, conducting market research with clinicians and people living with PBH, and developing disease education and market access strategies.

Based on published literature and claims analysis, management reiterated an estimate of approximately 160,000 people living with PBH in the U.S., out of more than 2 million people who underwent sleeve gastrectomy or Roux-en-Y gastric bypass over the last decade. Executives said claims work has also been used to better understand where patients are treated and to corroborate patient counts with centers.

The company said its data suggest a pattern typical of an orphan disease, with some centers caring for a concentrated pool of PBH patients and others seeing fewer. Management said this informs future deployment strategies if avexitide is approved.

Management also noted growing awareness of PBH, citing that PBH is now on endocrinology board exams and that the company expects to "hear on a potential ICD-10 code this year," with more expected in April. An ICD-10 code could help with identifying PBH patients in claims data and within health systems, while the company does not view an ICD-10 code as necessary for future reimbursement.