Amylyx Pharmaceuticals (AMLX) Study result summary

Study design and objectives

• Phase III LUCIDITY trial was a multicenter, randomized, double-blind, placebo-controlled study with 78 adults who had post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass, randomized 3:2 to avexitide 90 mg daily or placebo.

• Participants had undergone surgery at least 12 months prior and had a clinical diagnosis of PBH.

• The trial included a 16-week double-blind period followed by a 32-week open-label extension, with over 90% completing the double-blind phase.

• Primary endpoint: composite rate of Level 2 (glucose <54 mg/dL) and Level 3 (requiring assistance) hypoglycemic events through week 16.

• Secondary endpoints: Level 2 events by SMBG and CGM, and Level 3 events.

Key efficacy and safety results

• Avexitide achieved a 55% reduction in composite Level 2 and Level 3 hypoglycemic events versus placebo (p=0.000003), meeting all primary and secondary endpoints.

• Statistically significant and clinically meaningful reductions were observed in all secondary endpoints, including Level 2 (SMBG and CGM) and Level 3 events.

• Efficacy was robust across baseline disease severity and all measured event types, with no small group driving results.

• Avexitide was generally well-tolerated; most adverse events were mild or moderate, with no serious events related to treatment.

• Most common adverse events: diarrhea, injection site erythema/redness, and bruising; no changes in body weight observed.

Clinical and patient impact

• PBH is a rare, chronic condition affecting about 160,000 people in the U.S., with significant quality-of-life impact.

• Avexitide addresses a major unmet need, as current options are largely ineffective and there are no FDA-approved therapies.

• Reductions in hypoglycemic events are expected to improve independence, safety, and daily functioning.

• Patients and clinicians express high enthusiasm for avexitide, with strong intent to use upon approval.

• Adherence is anticipated to be high due to the symptomatic nature of PBH and lack of alternatives.