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Months after withdrawing its only approved product from the market, Amyrix Pharmaceuticals looks set to make a comeback, this time in the hot GLP-1 space. The company isn’t going after obesity indications, though. Instead, Amyrix has chosen a mid-stage candidate that could be a breakthrough treatment for other conditions related to blood sugar balance.
Earlier this month, the company announced it was buying a drug candidate called Avexitide, which is ready for Phase 3 clinical trials, for $35 million. Eiger Biopharmaceuticals bankruptcy auction.
The candidate targets the GLP-1 hormone, but unlike blockbuster obesity drugs that act as GLP-1 agonists, avexitide is an antagonist that lowers insulin levels while raising blood sugar. So far, the drug has shown promise in two conditions characterized by this one-two punch: hypoglycemia after bariatric surgery and congenital hyperinsulinemia. Given the drug’s clinical track record, Amyrix hopes to initiate one late-stage trial in the first quarter of 2025, with data readout in 2026 and a launch the following year.
“We want to balance normal glycemic control and response, and (avexitide) has the potential to be a breakthrough drug to manage diseases associated with that.”
Justin Clay
Co-CEO, Amyrix Pharmaceuticals
The company is not currently offering guidance on market potential for either indication, but Amyrix co-CEOs Josh Cohen and Justin Cree said that bariatric hypoglycemia affects approximately 160,000 people in the U.S.
“This is a really disabling disease,” Cree said. “Many of these patients don’t leave their homes and require around-the-clock care because they don’t know when they’re going to have an unexpected seizure or blackout or whatever.”
If approved, avexitide could provide a needed new option for both indications.
“We think avexitide has great potential,” Cree says, “and the data has got our staff very excited.”
The move into endocrine diseases marks another big milestone for Amylyx.
The FDA approved the company’s ALS treatment, Relyvrio, in 2022 based on positive interim data suggesting it could slow the progression of the disease. But results from a confirmatory trial this spring found it to be no more effective than a placebo. Following the disappointing results, Amyrix pulled Relyvrio from the market and laid off about 100 employees. 70% of employees.
Amyrix, which has roots in the neurodegeneration field, is continuing to study the compound. The drug, called AMX0035, is in clinical trials. Middle stage development of Wolfram syndromea rare genetic disorder that can be fatal.
Amyrix also has a promising new drug in early development, AMX0114, which targets calpain 2, for the treatment of ALS. Associated with neuronal death.
Here, Cohen and Cree reflect on what they learned from their experience with Relyvrio and how they’re applying those lessons to other candidates.
This interview has been edited for clarity and style.
PHARMAVOICE: What is the biggest lesson you learned from your experience with Relyvrio’s failure in ALS?
Justin Cree: What I’m really proud of is the study that we conducted, and I think our team as well, who conducted a large, multinational, complex Phase 3 study and did it efficiently with a patient-centric design.
The challenge is that these are difficult areas to develop. Although the results were not what we expected, the trials went well. The main lesson is that we have the team, resources and operations to develop these promising treatments and, if they work, bring them to thousands of people.
Josh Cohen: Another thing we’re excited about for future trials is the use of biomarkers, which is inherently difficult in ALS, but we’ve made great progress. Our next trials in ALS will leverage a lot of the recent biomarker insights to increase our confidence as we get more data.
We are looking at biomarkers for Wolfram syndrome as well, but with avexitide we have the advantage of looking at objective measures such as hemoglobin A1C (blood glucose level), which is one of the oldest biomarkers.
Has Relyvrio’s failure caused you to rethink the science behind the drug and your approach to ALS?
clay: We continue to believe strongly that targeting neurodegenerative pathways in these diseases is crucial — what has changed is that our understanding of those pathways has improved and our ability to target them has improved.
Our therapy (AMX0114 in ALS) has been studied as a target for decades. But targeting calpain 2 alone and getting enough exposure to the brain and spinal cord is challenging. Now we have antisense oligonucleotides that we can administer, so we know we’re hitting calpain 2 alone, and we’re getting exposure to the brain and spinal cord at therapeutic doses. Our approaches to target neurodegeneration in a meaningful way have grown exponentially.
Cohen: A lot of great research continues to happen in ALS, and we’ve gotten better at measuring outcomes. We’ve gotten better at looking at biomarkers, there’s been a lot of thought and discussion about how to distinguish signal from noise, and there’s a lot of publications on the basic biology around genetics and so forth. ALS has benefited from a fair bit of research being done, especially for a rare disease, and we try to follow the literature closely. We’ve always made a list of the most interesting targets we should pursue, and calpain 2 has long been the one we were most excited about. It was one of those targets that we felt was unfortunate that it wasn’t pursued in the right way.
Avexitide is being developed as a treatment for hypoglycemia following bariatric surgery, but there is also evidence that the effectiveness of GLP-1 agonists is reducing the demand for bariatric surgery. What does the long-term market for Avexitide look like?
clay: GLP-1 is one of the master regulators of glucose insulin balance, so agonists of this receptor have been shown to be effective in a variety of diseases and conditions. So in these diseases, agonists of the GLP-1 receptor are beneficial. But this is only half of the equation. And the other half, hypoglycemia and hyperinsulinemia, we still don’t have enough success with. We want to balance normal glycemic control and response, and this drug could be a breakthrough drug to manage diseases related to that.
Bariatric surgery is done for many reasons other than weight loss. At least 2 million of the most common bariatric surgeries have been performed in the United States in the past decade, amounting to well over 200,000 per year. GLP-1 agonists may reduce this number, but even a 10% reduction would still be a significant number of surgeries being performed.
Additionally, I’ve heard some counterarguments: As weight loss becomes more mainstream and talked about, doctors in some clinics are seeing an increase in the number of bariatric surgeries due to this increased awareness.
The last time we interviewed you two, Co-CEO model And why is it a good fit for the pharmaceutical industry? How has this model performed during these past few months of crisis?
clay: Again, that was a real blessing. You have limited time to make really important decisions. It’s a lot easier if you have people you can trust and feel like you can share the burden of what needs to be addressed. But in a broader sense, we were really lucky to have such a great team that aligned right away. There were no arguments or disagreements. We were just figuring out how to best do what we needed to do. It was a challenging time, but I’m proud that we were able to provide free access to ALS patients who wanted to continue taking the medication, while being transparent about our results.
Cohen: The strength of the Co-CEO model is even greater during times of crisis, when there aren’t enough hours in the day and the emotional toll is high. In those situations, having multiple leaders helps to solve all the problems.
