Amylyx Pharmaceuticals NASDAQ: AMLX is preparing for a pivotal Phase 3 readout for AVEXITIDE, its lead asset for post-bariatric hypoglycemia, or PBH, with data from the LUCIDITY trial expected in the third quarter, Co-Chief Executive Officer Joshua Cohen said at the BofA Annual Healthcare Conference.
In a discussion led by BofA analyst Jason Gerber, Cohen described the upcoming data as central to the company’s near-term outlook and said the trial was designed to closely mirror earlier studies that showed statistically significant effects on glucose and insulin, as well as reductions in severe hypoglycemic events.
“We’re very excited about the Phase III readout expected next quarter,” Cohen said. “AVEXITIDE, our lead asset, has been through five prior trials, all of which showed highly statistically significant effects on glucose and insulin.”
Phase 3 Trial Designed to Replicate Earlier Results
Cohen said Amylyx sought to keep the Phase 3 LUCIDITY trial consistent with earlier Phase 2 and Phase 2b studies, including similar inclusion and exclusion criteria and endpoint assessment. The Phase 2 and Phase 2b studies required patients to have at least two severe hypoglycemic events over two weeks, while the Phase 3 trial requires at least three severe events over three weeks, maintaining an event-rate threshold of roughly one per week.
The key difference is duration. The prior studies lasted four weeks, while LUCIDITY runs for 16 weeks. Cohen said the company does not expect the longer duration to reduce the treatment effect, noting that Amylyx has not seen signals such as anti-drug antibodies that would suggest attenuation over time.
Gerber cited statistical assumptions for LUCIDITY, including 90% power to detect a 35% effect size and a 50% placebo response. Cohen said the company powered the study conservatively and does not expect a placebo response of that magnitude, because patients with PBH are already taking steps to avoid severe hypoglycemia.
“We powered to see a 35% relative rate reduction, but in Phase II we saw 55%. In Phase II-B, a 64%,” Cohen said. “We were conservative in all the statistical assumptions, in part because this is the first Phase III.”
Aiming at an Underserved PBH Population
Cohen characterized PBH as a severe and underserved condition with no approved therapies. He said patients experience recurrent, dramatic drops in blood sugar that may occur after meals or be triggered by exercise, stress or other factors. These events can cause dizziness, loss of consciousness, falls, car accidents or seizures, and many patients describe themselves as disabled because they cannot drive or need someone nearby in case they lose consciousness.
He contrasted AVEXITIDE with acarbose, an alpha-glucosidase inhibitor sometimes used off-label. Cohen said acarbose does not address what Amylyx views as the underlying mechanism of PBH and can cause gastrointestinal side effects that make it difficult for patients to remain on therapy.
According to Cohen, PBH involves faster nutrient transit that drives an exaggerated GLP-1 response. AVEXITIDE is a GLP-1 antagonist, which he said targets what Amylyx believes is the core mechanism of the condition.
“There’s nothing available today that’s been proven to do anything to these hypoglycemic events,” Cohen said. “To potentially have a therapeutic that could impact that, as we’ve done market research, the intent to treat does seem high.”
NDA Preparation and Potential 2027 Launch
If the Phase 3 data are positive, Cohen said Amylyx intends to submit a new drug application as quickly as possible. He said the company has tried to complete as much of the application as possible ahead of the data readout so that it can incorporate results once available, rather than begin the filing process afterward.
Cohen said there is no major chemistry, manufacturing and controls issue that the company expects would delay submission. Amylyx has Breakthrough Therapy designation for AVEXITIDE, and Cohen said the company expects the typical two-month filing period and six-month priority review associated with that designation. The company’s goal is to enable a 2027 launch.
On regulatory interactions, Cohen said Amylyx has had “business as usual” discussions with the FDA and noted that the LUCIDITY protocol was submitted and reviewed before the trial began. He said the study uses a placebo-controlled design and a well-established endpoint: hypoglycemia.
Market Size, Access and Commercial Build
Cohen said Amylyx estimates there are about 160,000 people in the U.S. with PBH. He said that estimate is based on published literature, including prospective studies of bariatric surgery cohorts, as well as claims analyses identifying patients with bariatric surgery and subsequent unexplained hypoglycemia claims.
He said Amylyx further validated its claims work through blinded market research with sites that treat PBH patients, finding that claims estimates were generally aligned with the number of patients those sites reported seeing. Cohen also said Amylyx expects an ICD-10 code for PBH to become available in October.
Cohen said the company’s initial commercial focus would be on expert centers and high-volume sites serving PBH patients, while also educating physicians and patients. Some patients, he said, may need to be “reactivated” if they previously stopped seeing endocrinologists because there were no new treatment options available.
Amylyx is also running an expanded access program, initially enrolling patients who completed LUCIDITY or participated in prior AVEXITIDE trials. Cohen said many of those patients have contacted the company and are eager to return to therapy, though he said the expanded access program should not be viewed as a market-size indicator.
Discussing administration, Cohen said adherence in prior trials was strong and that Amylyx does not expect daily subcutaneous injection to be a major barrier, in part because patients with PBH already monitor blood glucose through finger sticks.
Pipeline Updates and Financial Position
Cohen said Amylyx has guided to a cash runway into 2028 and that its cash modeling does not include revenue, which he characterized as conservative. He said the company expects to be in a “very strong financial position” when Phase 3 data arrive in the third quarter.
The company is also working on a longer-acting GLP-1 antagonist developed with Gubra. Cohen said the molecule was designed to be at least once-weekly, if not better, but cautioned that its human pharmacokinetic profile will not be known until clinical testing begins. Amylyx expects to submit an investigational new drug application in 2027.
Cohen also discussed AMX0035 in Wolfram syndrome, a rare monogenic disease affecting an estimated 3,000 people in the U.S. He said Amylyx has presented 48-week Phase 2 data showing general stabilization or improvement across measured outcomes and plans to present 96-week data. The company is still working with the FDA on the design and primary endpoint for a potential Phase 3 trial.
While Cohen said Amylyx will consider its options for the Wolfram program, he emphasized that the company’s main priority remains AVEXITIDE and the upcoming LUCIDITY readout.
About Amylyx Pharmaceuticals NASDAQ: AMLX
Amylyx Pharmaceuticals, Inc is a biopharmaceutical company dedicated to developing treatments for rare and debilitating neurological diseases. Founded in 2013 and headquartered in Cambridge, Massachusetts, the company focuses on leveraging novel approaches to target cellular pathways implicated in neurodegeneration. Amylyx's research platform centers on small-molecule therapies designed to protect neurons and support cellular health in patients with conditions that currently have limited or no disease-modifying treatment options.
The company's lead product, AMX0035, is marketed under the trade name Relyvrio following U.S.
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