Amylyx Pharmaceuticals Announces Acquisition of Phase 3-ready GLP-1 Receptor Antagonist (Avexitide) with FDA Breakthrough Therapy Designation
Amylyx Pharmaceuticals has acquired avexitide, a first-in-class GLP-1 receptor antagonist, from Eiger BioPharmaceuticals for $35.1 million. Avexitide is designed to treat hyperinsulinemic hypoglycemia and has received FDA Breakthrough Therapy Designation for post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism (HI). The Phase 3 trial for PBH is set to begin in Q1 2025, with results expected in 2026. Two Phase 2 trials demonstrated significant reductions in hypoglycemic events, and avexitide showed a favorable safety profile. Amylyx will incorporate avexitide into its existing pipeline, bolstering its focus on treating endocrine and neuroscience disorders.
- Acquisition of avexitide for $35.1 million, expanding Amylyx's pipeline.
- Avexitide has FDA Breakthrough Therapy Designation for PBH and HI.
- Successful Phase 2 trials showed significant reductions in hypoglycemic events.
- Avexitide exhibited a favorable safety profile across five clinical trials.
- Phase 3 trial for PBH to begin in Q1 2025, with data readout in 2026.
- Assumed liabilities and a 3% royalty on future sales of avexitide.
Insights
Financial Perspective: Amylyx Pharmaceuticals' acquisition of avexitide for
Investors should watch for cost management, potential dilution of shares to fund trials and how this acquisition might affect Amylyx's existing research commitments.
Clinical Insights: Avexitide’s prior Phase 2 trials exhibited significant reductions in hypoglycemic events, holding promise for Phase 3. The Breakthrough Therapy Designation underlines its potential impact on post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism (HI). The FDA's agreement on the primary endpoint for Phase 3 is a positive indicator, though investors should understand that success isn't guaranteed. The asset’s tolerability and safety profile, with no severe reported adverse events, enhances its potential for regulatory approval.
Investors should consider the long-term benefits of avexitide potentially addressing unmet medical needs, while acknowledging the inherent risks of clinical trial phases.
Market Dynamics: The acquisition of avexitide allows Amylyx to further penetrate the endocrine and metabolic disorder market. Given the high unmet needs in PBH and congenital HI, the drug could capture significant market share if approved. The breakthrough designation and orphan drug status might expedite the approval process and grant market exclusivity, enhancing market potential. However, competition from other therapies and the regulatory landscape must be monitored. The expected Phase 3 results in 2026 could pivotally influence market positioning and investor sentiment.
Investors should anticipate fluctuations based on trial progress and be aware of potential competition and regulatory hurdles that could impact market entry and penetration.
- Avexitide is a novel, first-in-class GLP-1 receptor antagonist with the potential to treat hyperinsulinemic hypoglycemia
- FDA Breakthrough Therapy Designation granted for avexitide for post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism
- Acquisition builds on Amylyx’ endocrine and neuroscience expertise and aligns with pipeline focus of delivering important potential treatment options to communities with high unmet needs
- Phase 3 program for avexitide in PBH expected to begin in Q1 2025, with data readout anticipated in 2026; FDA has agreed to the primary endpoint expected to be utilized in Phase 3
- Data from two Phase 2 studies of avexitide in people with PBH demonstrated highly statistically significant reductions in severe hypoglycemic events, an endpoint supported by the FDA
- Avexitide was generally well tolerated, with a favorable safety profile replicated across five clinical trials in people with PBH
- Management to host conference call and webcast today at 8:00 a.m. Eastern Time
“Since Amylyx was founded, we have been guided by a rigorous approach to our science to bring potential treatments to communities with high unmet needs. When we reviewed all the compelling data supporting avexitide, it clearly aligned with our strategic scientific criteria, expertise, and community values, and we are excited to build upon the important work done to date to study this asset,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx.
Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist that has been evaluated in five clinical trials for post-bariatric hypoglycemia (PBH) and has also been studied in congenital hyperinsulinism (HI), two indications characterized by hyperinsulinemic hypoglycemia. The
Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and block the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose levels. In PBH, excessive GLP-1 can lead to the hypersecretion of insulin and subsequent severe hypoglycemic events, including autonomic and neuroglycopenic symptoms if left unaddressed.
In previous Phase 2 and Phase 2b studies in PBH, avexitide showed statistically significant reductions in hypoglycemic events characterized by low blood glucose, including severe hypoglycemic events with altered mental and/or physical function requiring assistance. FDA guidance for industry combined with initial FDA feedback specific to the pivotal Phase 3 program of avexitide for PBH suggest that reduction in hypoglycemia events could be an endpoint to support approval following positive results from a pivotal Phase 3 clinical trial.
Amylyx expects to begin the Phase 3 program for avexitide in PBH in Q1 2025. Furthermore, Amylyx is actively engaging in discussions with the broader congenital HI community, including experts in the field, to develop a path forward based on promising Phase 2 study results conducted at Children's Hospital of
Avexitide in PBH: Key Clinical Trial Results to Date
The following table shows key results from the Phase 2, randomized, placebo-controlled crossover study (PREVENT) that evaluated efficacy and safety of avexitide for treatment of PBH following Roux-en-Y gastric bypass surgery. The results showed that, compared with placebo, avexitide 30 mg twice daily (BID) and 60 mg once daily (QD) significantly increased mean plasma glucose nadir (prespecified primary endpoint) and lowered insulin peak, corresponding to
Outcomea N=17 |
Avexitide 30 mg BID |
Avexitide 60 mg QD |
||
Improvement vs. Placebo |
p-value |
Improvement vs. Placebo |
p-value |
|
Post Prandial Glucose Nadir (Primary Endpoint) |
|
0.001 |
|
0.0002 |
Peak Insulin Level (Secondary Endpoint) |
|
0.029 |
|
0.042 |
Rate of Level 1 Hypoglycemia |
|
0.072 |
|
0.001 |
Rate of Level 2 Hypoglycemia |
|
0.040 |
|
0.004 |
Rate of Level 3 (Severe) Hypoglycemia |
|
0.22 |
|
0.014 |
aLevel 1 hypoglycemia: self-monitoring of blood glucose (SMBG) <70 mg/dL; Level 2 hypoglycemia: SMBG <54 mg/dL; Level 3 hypoglycemia: a severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. |
Avexitide was generally well tolerated. The most common adverse events were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose. No participants withdrew due to adverse events.
A Phase 2b open-label, investigator-initiated, cross-over study of higher dose avexitide (45 mg BID and 90 mg QD) was completed in a broader eligible population of 16 participants with PBH following Roux-en-Y gastric bypass surgery, vertical sleeve gastrectomy, esophagectomy, Nissen fundoplication, or gastrectomy. This trial met both its primary endpoint of number of diurnal Level 2 hypoglycemia events (glucose <54mg/dL) as measured by CGM as well as its secondary endpoints, which includes the rate of Level 2 hypoglycemia, rate of Level 3 hypoglycemia, percent diurnal time <70 mg/dL as measured by CGM, and percent diurnal time <54 mg/dL as measured by CGM.
Avexitide was successful in reducing the frequency of hypoglycemia up to
Outcome N=16 |
Avexitide 45 mg BID |
Avexitide 90 mg QD |
||
Decrease from Baseline |
p-value |
Decrease from Baseline |
p-value |
|
Rate of Level 1 Hypoglycemia |
|
0.003 |
|
0.0005 |
Rate of Level 2 Hypoglycemia (Secondary Endpoint)a |
|
0.003 |
|
0.004 |
Rate of Level 3 (Severe) Hypoglycemia (Secondary Endpoint)b |
|
0.0003 |
|
0.0003 |
aRate of Level 2 hypoglycemia: self-monitoring of blood glucose (SMBG) <54 mg/dL. |
||||
bRate of Level 3 hypoglycemia: severe event characterized by altered mental and/or physical function requiring assistance. |
There were no reported serious adverse events, and adverse events were mostly mild to moderate and resolved without medical treatment. The most common adverse events included diarrhea, headache, bloating, and injection site reaction/bruising. No participant withdrew due to adverse events.
“PBH is a debilitating condition with no approved treatment options, and we look forward to advancing this critical work with avexitide into Phase 3 for individuals with PBH based on the totality of data from five clinical trials, and informed by our ongoing work to address endocrine and metabolic aspects of Wolfram syndrome. We also are continuing our conversations with the congenital HI community regarding the clinical development of avexitide in congenital HI to develop a path forward,” said Camille L. Bedrosian, MD, Chief Medical Officer of Amylyx. “While we are excited to study this new scientific pathway in hyperinsulinemic hypoglycemia, our research in ALS and other neurodegenerative diseases continues through our AMX0035 and AMX0114 programs, guided by the understanding that people living with these devastating diseases have no time to wait – we must continue to research and collaborate with urgency.”
Transaction Details
On July 9, 2024, Amylyx completed the acquisition of substantially all of the rights, title and interests in, to and under those assets and interests used by the seller in the development, manufacture and commercialization of avexitide from Eiger for
Investor Conference Call Information
Amylyx’ management team will host a conference call and webcast today, July 10, 2024, at 8:00 a.m. ET to discuss the asset acquisition. To access the conference call, please dial +1 (800) 836-8184 (
About Avexitide
Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist that has been evaluated in five Phase 2 clinical studies for post-bariatric hypoglycemia (PBH) and has also been studied in congenital hyperinsulinism (HI), with
About Post-Bariatric Hypoglycemia (PBH)
Symptomatic post-bariatric hypoglycemia (PBH) is a condition that affects approximately
About Congenital Hyperinsulinism (HI)
Congenital hyperinsulinism (HI) is a rare disease characterized by hypersecretion of insulin leading to severe, persistent hypoglycemia in infants and young children with limited therapeutic options. Common symptoms of congenital HI include lack of energy, irritability, lethargy, and excessive hunger. Repeated episodes of low blood glucose increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma.
About AMX0035
AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the
About AMX0114
AMX0114 is an antisense oligonucleotide designed to target the gene encoding calpain-2, a key contributor to the axonal (Wallerian) degeneration pathway. Axonal degeneration has been recognized as an important early contributor to the clinical presentation and pathogenesis of ALS and other neurodegenerative diseases. Calpain-2 has been implicated in the pathogenesis of ALS based on findings of elevated levels of calpain-2 and its cleavage products in postmortem ALS tissue, therapeutic benefit of calpain-2 modulation in animal models of ALS, and the role of calpain-2 in cleaving neurofilament, a broadly researched biomarker in ALS. Preclinical studies completed to date have shown that AMX0114 achieves potent, dose-dependent, and durable knockdown of CAPN2 mRNA expression and calpain-2 protein levels in human motor neurons. Moreover, in preclinical efficacy studies, treatment with AMX0114 reduced extracellular neurofilament light chain levels following neurotoxic insult in induced pluripotent stem cell (iPSC)-derived human motor neurons, and improved survival of iPSC-derived human motor neurons harboring ALS-linked, pathogenic TDP-43 mutations.
About Amylyx Pharmaceuticals
Amylyx is committed to the discovery and development of new treatment options for communities with high unmet needs, including people living with serious and fatal diseases. Since its founding, Amylyx has been guided by science to address unanswered questions, keeping communities at the heart and center of all decisions. Amylyx is headquartered in
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, Amylyx’ expectations regarding: plans for initiating a Phase 3 clinical program of avexitide, including interactions with regulatory authorities; the possibility that results from a Phase 3 program could support FDA approval of avexitide in PBH; and expectations regarding the benefits of the acquisition of avexitide. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
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Source: Amylyx Pharmaceuticals, Inc.
FAQ
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