Amylyx Pharmaceuticals Announces Positive Topline Results from Phase 2 HELIOS Clinical Trial Demonstrating Sustained Improvements with AMX0035 in People Living with Wolfram Syndrome
Amylyx Pharmaceuticals (NASDAQ: AMLX) announced positive topline results from its Phase 2 HELIOS clinical trial of AMX0035 in adults with Wolfram syndrome. The trial showed improvement in pancreatic function after 24 weeks of treatment, contrary to expected disease progression. Improvements or stabilization were observed across all secondary endpoints, including glycemic control, vision, and patient- and clinician-reported impressions of disease burden.
Key findings include:
- Sustained improvement over time in longer-term data for participants completing Week 36 and Week 48 assessments
- AMX0035 was generally well-tolerated
- Amylyx plans to meet with the FDA to inform a Phase 3 program, with an update expected in 2025
The results suggest AMX0035 has the potential to favorably change the trajectory of Wolfram syndrome, a rare, progressive disease with no approved treatment options.
- Improvement in pancreatic function (C-peptide response) after 24 weeks of AMX0035 treatment
- Sustained improvement observed in longer-term data (Week 36 and Week 48)
- Improvements or stabilization across all secondary endpoints (glycemic control, vision, disease burden)
- AMX0035 was generally well-tolerated with no serious adverse events related to treatment
- FDA and European Commission granted Orphan Drug Designation for AMX0035 in Wolfram syndrome
- None.
Insights
The HELIOS Phase 2 trial results for AMX0035 in Wolfram syndrome are highly encouraging. Key findings include:
- Improvement in pancreatic function (C-peptide response) after 24 weeks, contrary to expected disease progression
- Sustained improvements at 36 and 48 weeks in C-peptide and HbA1c levels
- Positive trends across secondary endpoints including glycemic control and visual acuity
- 100% of participants showing disease stability or improvement on global impression scales
These results suggest AMX0035 may potentially alter the disease course of Wolfram syndrome, which currently has no approved treatments. The sustained improvements over 48 weeks are particularly noteworthy given the progressive nature of the disease. The safety profile appears favorable, with only mild to moderate adverse events reported.
While promising, it's important to note the small sample size (12 participants) and open-label design. A larger, randomized controlled Phase 3 trial will be important to confirm efficacy and safety. Amylyx's plan to meet with the FDA to discuss a Phase 3 program is a positive next step for advancing this potential treatment.
This news is significantly positive for Amylyx Pharmaceuticals. Key financial implications include:
- Potential expansion of AMX0035 into a new indication beyond ALS, diversifying the company's pipeline
- Orphan Drug Designation in both US and EU markets, providing regulatory benefits and market exclusivity if approved
- Addressing an unmet medical need in a rare disease with no approved treatments, potentially commanding premium pricing
- Positive data supporting further investment in a Phase 3 program, de-risking the development pathway
However, investors should consider that:
- A Phase 3 trial will require significant additional investment
- Market size for Wolfram syndrome is (
~3,000 patients in the US) - Timeline to potential approval and commercialization is still several years out
Overall, this news strengthens Amylyx's position in rare neurodegenerative diseases and could drive long-term value creation if AMX0035 advances successfully in Wolfram syndrome.
- Improvement observed in pancreatic function, as measured by C-peptide response, following 24 weeks of treatment with AMX0035; worsening is typically expected with disease progression based on natural history studies of Wolfram syndrome
- Longer-term data for all participants who have completed Week 36 and Week 48 assessments showed sustained improvement over time
- Improvements or stabilization observed across all secondary endpoints, including measures of glycemic control, vision, and patient- and clinician-reported impressions of overall disease burden
- AMX0035 was generally well-tolerated in all participants
- Amylyx plans to meet with the FDA and other stakeholders to inform a Phase 3 program and expects to provide an update in 2025
- Topline data to be presented during a live webcast today at 1:30 p.m. ET
In addition, longer-term data for all participants who completed Week 36 (n=10) and Week 48 (n=6) assessments showed sustained improvement over time. Data from HELIOS are being presented today at the International Society for Pediatric and Adolescent Diabetes (ISPAD) 50th Annual Congress and during a webcast held by the Company.
“The topline results of HELIOS indicate that AMX0035 has the potential to favorably change the trajectory of Wolfram syndrome, a progressive disease with no approved treatment options. These results build on the interim data presented in April of this year and show an improvement on multiple measures of pancreatic beta cell function, glycemic control, and vision,” said Fumihiko Urano, MD, PhD, Principal Investigator of the Phase 2 HELIOS clinical trial in Wolfram syndrome and the Samuel E. Schechter Professor of Medicine in the Division of Endocrinology, Metabolism & Lipid Research at Washington University School of Medicine in
The analysis performed includes Week 24 data for all 12 participants and data for all participants who completed their Week 36 (n=10) and Week 48 (n=6) assessments as of the data cutoff. The primary efficacy endpoint of the trial measures change from baseline in C-peptide, an established, objective laboratory measure of pancreatic beta cell function and a surrogate marker of glycemic control, assessed using a mixed meal tolerance test (MMTT) at Week 24. Secondary and exploratory outcomes include the assessment of other diabetic measures and other domains affected by the disease.
HELIOS showed improvements in its primary endpoint of C-peptide response with a change from baseline to Week 24 at 120 minutes of +3.8 minutes*ng/mL (min*ng/mL) [standard error (SE): 19.3] in the Intent to Treat group (N=12) and +20.2 min*ng/mL [SE: 11.2] in the Per Protocol group (N=11). In addition, as outlined in the table below, participants receiving AMX0035 had improved glycemic control, as measured by markers of glucose metabolism; improved visual acuity in some participants, as measured by the Snellen chart; and improvement or stabilization of the disease, as measured by the Clinician Reported Global Impression of Change (CGIC) and Patient Reported Global Impression of Change (PGIC).
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Week 24
|
Week 24 Per Protocol†
|
Week 36 (n=10) |
Week 48 (n=6) |
C-Peptide Response (min*ng/mL)
|
+3.8
|
+20.2
|
+30.7
|
+36.7
|
Hemoglobin A1c (%)
|
-0.09
|
-0.16
|
-0.35
|
-0.30
|
Absolute Time in Target Glucose Range (%)
|
+5.2
|
+5.7
|
+12.3
|
+5.8
|
Mean Exogenous Insulin Dose
change from baseline |
-0.01 |
-0.01 |
0.01 |
0.02 |
Visual Acuity
|
-0.04
|
-0.04
|
Not Collected at this Time Point |
-0.11
|
Clinician Report Global Impression of Change (CGIC)
|
|
|
|
|
Patient Reported Global Impression of Change (PGIC)
|
|
|
|
|
† Upon genetic review, one participant did not meet the inclusion/exclusion criteria for HELIOS. This participant was found to have an autosomal recessive mutation confirmed to be pathogenic on just one of the two alleles and variant of uncertain significance on the other allele. This participant was within normal range for C-peptide, glycemic measures, and vision suggesting lack of typical Wolfram syndrome phenotype. Data presented with and without this participant who reached Week 24 (Intent to Treat and Per Protocol, respectively). |
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†† In non-diabetic individuals, C-peptide peaks after a meal at approximately ~30 minutes; in Wolfram syndrome, peak is slower but generally was at or before 120 minutes in HELIOS. Area under the curve (AUC) over 120 minutes after meal challenge reflects beta cell response to a meal. Amylyx is currently planning to focus on 120-minute AUC as the C-peptide measure for future studies. |
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††† HELIOS defines a “responder” on both the CGIC and PGIC as no change or improvement given the progressive nature of Wolfram syndrome. |
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The safety profile of AMX0035 in HELIOS was consistent with prior safety data. AMX0035 was generally well-tolerated. All adverse events (AEs) were mild or moderate, and there were no serious AEs related to AMX0035 treatment. The most common AE was diarrhea.
“These outcomes indicate that treatment with AMX0035 may result in meaningful improvements across multiple measures of disease progression,” said Camille L. Bedrosian, MD, Chief Medical Officer of Amylyx. “Wolfram syndrome is a progressive disease that is expected to consistently worsen over time, despite best supportive care, because of the underlying endoplasmic reticulum stress and mitochondrial dysfunction that occurs due to mutations in the WSF1 gene. AMX0035 is believed to target both of these critical pathways. In addition, we are encouraged by the sustained improvement observed in all participants who completed Week 36 or Week 48 assessments, and we thank the Wolfram syndrome community for their continued collaboration and support in researching the potential of AMX0035. We continue to engage with stakeholders and plan to meet with the FDA to inform a Phase 3 program.”
The FDA and the European Commission granted Orphan Drug Designation to AMX0035 for the treatment of Wolfram syndrome in November 2020 and August 2024, respectively.
HELIOS Interim Data in Wolfram Syndrome Virtual Webcast Details
Amylyx will host a virtual webcast with management and Fumihiko Urano, MD, PhD, Principal Investigator of the HELIOS clinical trial and the Samuel E. Schechter Professor of Medicine in the Division of Endocrinology, Metabolism & Lipid Research at Washington University School of Medicine in
About the HELIOS Trial
HELIOS (NCT05676034) is a 12-participant, single-site, single-arm, open-label, proof of biology, 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. Participants in HELIOS receive AMX0035 for up to 96 weeks followed by a four-week safety follow-up. Primary and secondary outcomes are assessed at Week 24 and at longer-term time points.
In September 2022, researchers from Washington University School of Medicine in
About Wolfram Syndrome
Wolfram syndrome is a rare, monogenic neurodegenerative 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. Genetic and experimental evidence suggests that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of Wolfram syndrome. The prognosis of Wolfram syndrome is poor, and many people with the disease die prematurely with severe neurological disabilities.
About AMX0035
AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the
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 neurodegenerative diseases and endocrine conditions. 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: the potential clinical benefit for AMX0035 to help people living with Wolfram syndrome; and interactions with regulatory authorities. 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’ Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, 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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FAQ
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