Amylyx Pharmaceuticals has ridden a wave of high-profile wins and setbacks in recent years. Now, the company is gearing up for another pivotal moment — a key readout that could largely determine its fate.
Within the next few months, Amylyx plans to finish recruitment for a pivotal study of its late-stage candidate avexitide, with topline data expected by the third quarter of 2026. If all goes well, the company might gun for an approval in 2027, potentially tapping into a market it could have all to itself.
Avexitide was developed to treat post-bariatric hypoglycemia — a condition that can afflict about 8% of patients who’ve undergone bariatric surgery, according to Dr. Camille Bedrosian, Amylyx’s chief medical officer.
While it may seem counterintuitive to target a population tied to bariatric surgeries amid the soaring popularity of GLP-1s, there are key distinctions between patient groups in the obesity space. In particular, bariatric surgery often remains the better option for patients more than 100 pounds overweight, Bedrosian said.
The surgery also remains popular. Although the number of procedures fell from 279,967 in 2022 to 270,089 in 2023, it was still at its second highest level in the past 15 years, according to the American Society for Metabolic and Bariatric Surgery.
For the roughly 160,000 patients Amylyx estimates are living with PBH in the U.S., the episodes of hypoglycemia that characterize the condition can trigger profound neurological symptoms, seizures and weakness, rendering them unable to take care of themselves or others.
“What we learned working with the community about the lives of these individuals is that they can become very sheltered, fearful of driving or going out,” Bedrosian said.
There are currently no approved treatments for PBH and although avexitide hasn’t shown signals of being a cure, it’s delivered positive results in the clinic. In particular, avexitide, which is a GLP-1 antagonist — as opposed to the GLP-1 agonists approved for weight loss — demonstrated a 64% reduction in moderate to severe events in a phase 2 trial.
Amylyx picked up the late-stage asset in Eiger BioPharmaceuticals’ bankruptcy auction last summer for $35 million after coming across the opportunity as part of its ongoing effort to broaden its pipeline. The company has, in fact, done due diligence on over 300 molecules during its history, Bedrosian said, and keeping its pipeline robust has remained a crucial strategy while weathering various challenges.
Most notably, Amylyx pulled its drug Relyvrio from the market last year after it was heralded as the first disease-modifying treatment for ALS and granted a conditional approval by the FDA, before failing a confirmatory trial.
More recently, Amylyx axed a program in August for the same drug — known in the clinic as AMX0035 — after it flunked a phase 2 study for progressive supranuclear palsy.
While Amylyx has pinned its hopes on avexitide becoming its first drug to reach and stay on the market, it’s still keeping its foot in the neurodegenerative space.
The endocrine-neuro disease bridge
When Bedrosian was deciding if she wanted to come aboard Amylyx before officially joining in 2023, she told co-CEOs Josh Cohen and Justin Klee she wanted to make sure the company would maintain a focus on ALS.
“ALS is the quintessential neurodegenerative disease,” she explained. “It’s the final frontier because it’s so hard to dissect and treat. So that’s something I wanted to be a part of.”
To that end, Amylyx is in early clinical trials with an experimental antisense oligonucleotide targeting calpain-2, which plays a role in cell signaling and is linked to neurodegeneration. The candidate, AMX0114, won a fast track designation from the FDA in June.
Amylyx also hasn’t given up on AMX0035 and is testing the combination therapy for the rare genetic disease Wolfram syndrome. The company recently reported new long-term phase 2 results showing a durable response for multiple outcomes related to disease progression. Amylyx is now working with the FDA on designing a pivotal phase 3 trial and is aiming to publish more updates and data from the program by the second half of 2026, Bedrosian said.
While its pipeline may stretch into different therapeutic areas, Amylyx researchers have seen an “interplay” between the endocrine system linked to PBH and neurodegeneration through its studies of Wolfram syndrome and the C peptide biomarker.
“Our long-term vision is to develop novel therapies for fatal disorders and diseases with high unmet need, but the biology also has to fit,” Bedrosian said.
Investors are continuing to buy into that goal. Two fundraising rounds this year through common stock offerings have helped Amylyx build a cash runway that will last into 2028, Bedrosian said.
And despite concerns it wouldn’t survive its setbacks in ALS, Bedrosian said Amylyx isn’t going anywhere.
“We were getting back on our feet [in 2024] … now, we’re in a resurgence,” she said.
