Amylyx Pharmaceuticals Receives Orphan Drug Designation From the European Commission for AMX0035 for the Treatment of Wolfram Syndrome

Rhea-AI Summary

Amylyx Pharmaceuticals (NASDAQ: AMLX) has received Orphan Drug Designation from the European Commission for AMX0035 to treat Wolfram syndrome. This follows a similar designation by the FDA in 2020. Wolfram syndrome is a rare, progressive disease characterized by childhood-onset diabetes and neurodegeneration, with no approved treatments. Interim data from the Phase 2 HELIOS trial showed AMX0035 improved pancreatic function and glycemic control in 8 participants at Week 24. The drug was generally well-tolerated, with patients reporting disease improvement or stabilization. Topline data for all 12 participants is expected in fall 2024.

Positive

• Received Orphan Drug Designation from European Commission for AMX0035 in Wolfram syndrome
• Positive interim data from Phase 2 HELIOS trial showing improved pancreatic function and glycemic control
• All 8 participants in interim analysis met prespecified responder criteria for disease improvement or stabilization
• AMX0035 was generally well-tolerated in all participants

Negative

• None.

Medical Research Analyst

The European Commission's Orphan Drug Designation for AMX0035 in Wolfram syndrome is a significant development for Amylyx Pharmaceuticals. This designation, following the FDA's similar recognition in 2020, underscores the potential of AMX0035 in addressing a rare and severe condition with no current approved treatments.

The interim results from the Phase 2 HELIOS trial are particularly noteworthy:

• Improvement in pancreatic function and glycemic control, as evidenced by changes in C-peptide and HbA1c levels
• Disease stabilization or improvement reported by both patients and clinicians
• Potential visual improvements in some participants

These outcomes are remarkable given the progressive nature of Wolfram syndrome. The stabilization or improvement in multiple domains suggests that AMX0035 may be effectively targeting the underlying pathophysiology of the disease, particularly endoplasmic reticulum stress.

However, it's important to note that these results are based on an interim analysis of only eight participants. The upcoming topline data from all 12 participants will provide a more comprehensive understanding of the drug's efficacy and safety profile. If these positive trends continue, AMX0035 could potentially become the first approved treatment for Wolfram syndrome, addressing a significant unmet medical need.

The mechanism of action of AMX0035, targeting both ER stress and mitochondrial dysfunction, aligns well with the pathophysiology of Wolfram syndrome. This targeted approach, combined with the positive interim results, suggests a promising path forward for this therapy.

Financial Analyst

The Orphan Drug Designation from the European Commission for AMX0035 in Wolfram syndrome represents a significant milestone for Amylyx Pharmaceuticals. This designation, coupled with the FDA's previous recognition, positions AMX0035 favorably in both major pharmaceutical markets.

Key financial implications include:

• Market exclusivity: Orphan Drug Designation typically grants 10 years of market exclusivity in the EU upon approval, providing a substantial competitive advantage.
• Development incentives: The designation may offer financial benefits such as reduced regulatory fees and potential tax credits, lowering the overall development costs.
• Market potential: While Wolfram syndrome is rare, orphan drugs often command premium pricing, potentially leading to significant revenue streams if approved.

The positive interim results from the HELIOS trial further strengthen Amylyx's position. If the full dataset continues to show efficacy and safety, it could accelerate the path to market approval. This would be particularly impactful given the lack of approved treatments for Wolfram syndrome.

Investors should note that Amylyx is expanding AMX0035's potential beyond its current approval for ALS. This diversification strategy could mitigate risk and open up new revenue streams. However, it's important to remember that drug development, especially for rare diseases, carries inherent risks and uncertainties.

The anticipated fall 2024 topline data release will be a critical event for Amylyx. Positive results could significantly boost investor confidence and potentially lead to partnerships or increased institutional interest. Conversely, any setbacks could impact the company's valuation and future prospects.

- New designation follows the U.S. Food and Drug Administration (FDA) Orphan Drug Designation for AMX0035 in Wolfram syndrome granted in 2020

- Topline data for all 12 participants from Phase 2 HELIOS trial studying impact of AMX0035 on endocrine, metabolic, and neurodegenerative aspects of Wolfram syndrome anticipated fall 2024

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced the European Commission (EC), based on a positive opinion issued by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA), has granted Orphan Drug Designation for AMX0035, Amylyx’ proprietary, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the U.S.) for the treatment of Wolfram syndrome.

Wolfram syndrome is a prototypical disease of endoplasmic reticulum (ER) stress that is rare, progressive, and monogenic and is characterized by childhood-onset diabetes mellitus, optic nerve atrophy, deafness, diabetes insipidus, and neurodegeneration. There are currently no drugs approved for Wolfram syndrome, and many people with the disease die prematurely with severe neurological disabilities.

The FDA previously granted AMX0035 Orphan Drug Designation for the treatment of Wolfram syndrome in 2020. The EMA grants Orphan Drug Designation status for products intended for the treatment, prevention, or diagnosis of rare, life-threatening, or chronically debilitating conditions where the product may represent a significant benefit over existing treatments.

Amylyx recently presented positive data from an interim analysis of its Phase 2 HELIOS study, including eight participants with Wolfram syndrome assessed at Week 24, which demonstrated that AMX0035 improved pancreatic function and glycemic control, as measured by C-peptide, HbA1c, and other markers of glucose metabolism. All eight participants met prespecified responder criteria showing either improvement or stabilization of disease according to both the Patient Reported Global Impression of Change (PGIC) and the Clinical Reported Global Impression of Change (CGIC) scales. The majority of participants reported some improvement in vision. In Wolfram syndrome, progressive decline and worsening of outcomes would have been expected on all measures, so disease improvement or stabilization alone is clinically meaningful. AMX0035 was generally well tolerated in all participants. The Company anticipates reporting topline data from all 12 participants at Week 24 this fall.

“Wolfram syndrome is a disease where there are well-defined measurable biomarkers, rigorous supporting preclinical data, and clear rationale for our potential therapy based on its mechanism of action. Specifically, Wolfram syndrome is considered a prototypical endoplasmic reticulum (ER) stress disorder because of the clear link between WFS1 mutations and ER stress. AMX0035 is believed to target ER stress and mitochondrial dysfunction,” said Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx. “The interim data from HELIOS showed stabilization or even improvement across key outcomes at Week 24. HELIOS follows strong preclinical research with data showing clear effects in cellular and animal models. We look forward to reporting topline data from all participants at Week 24 this fall. We aim to address an urgent unmet medical need, given there are no approved treatment options for Wolfram syndrome.”

About Wolfram Syndrome

Wolfram syndrome is rare, progressive, monogenic disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of Wolfram syndrome include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. The prognosis of Wolfram syndrome is poor, and many people with the disease die prematurely with severe neurological disabilities. Literature suggests approximately 3,000 people are living with Wolfram syndrome in the United States.

Wolfram syndrome is often characterized as a prototypical disease of endoplasmic reticulum (ER) stress. ER stress and mitochondrial dysfunction are believed to drive the underlying disease pathophysiology in Wolfram syndrome. Individuals with Wolfram syndrome generally have mutations in the WFS1 gene, which encodes wolframin, a protein spanning the membrane of the ER. Wolframin is thought to play a role in protein folding and aid in the maintenance of ER function by regulating calcium levels. Loss of wolframin function leads to ER stress and impaired mitochondrial dynamics.

About AMX0035

AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the U.S.). AMX0035 was designed to slow or mitigate neurodegeneration by simultaneously targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. Preclinical studies have provided evidence that the proprietary combination of PB and TURSO and their complementary mechanisms of action targets cell death and better prevents neurodegeneration than targeting either mechanism of action alone. AMX0035 is being studied as a potential treatment in neurodegenerative diseases, including Wolfram syndrome and progressive supranuclear palsy (PSP).

About the HELIOS Trial

The HELIOS trial (NCT05676034) is a 12-participant, open-label Phase 2 trial designed to study the effect of AMX0035 on safety and tolerability, and various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome.

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. The Company has preclinical or clinical development programs underway in neurodegenerative, neuroendocrine, and endocrine 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 Cambridge, Massachusetts. For more information, visit amylyx.com and follow us on LinkedIn and X. For investors, please visit investors.amylyx.com.

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: interactions with regulatory authorities; the ongoing evaluation of AMX0035 in Wolfram syndrome, including that early-stage results may not reflect later-stage results and the timing for expected topline data in the HELIOS study; and the potential for AMX0035 to help people living with Wolfram syndrome. 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240802814317/en/

Media

Amylyx Media Team

+1 (857) 799-7274

amylyxmediateam@amylyx.com

Investors

Lindsey Allen

+1 (857) 320-6244

Investors@amylyx.com

Source: Amylyx Pharmaceuticals, Inc.

FAQ

What is the purpose of Amylyx's Phase 2 HELIOS trial for AMX0035 (AMLX)?

The HELIOS trial is studying the impact of AMX0035 on endocrine, metabolic, and neurodegenerative aspects of Wolfram syndrome, a rare disease with no approved treatments.

When will Amylyx (AMLX) report topline data for all participants in the HELIOS trial?

Amylyx anticipates reporting topline data for all 12 participants at Week 24 in fall 2024.

What were the key findings from the interim analysis of Amylyx's (AMLX) HELIOS trial?

The interim analysis showed AMX0035 improved pancreatic function and glycemic control in 8 participants at Week 24, with patients reporting disease improvement or stabilization.

What regulatory designations has Amylyx (AMLX) received for AMX0035 in Wolfram syndrome?

Amylyx has received Orphan Drug Designation for AMX0035 in Wolfram syndrome from both the European Commission and the U.S. FDA.