Phase 3 PHOENIX Study of AMX0035 in ALS Gets Under Way

The first patients have been dosed in the phase 3 PHOENIX study (NCT05021536), a global study evaluating the safety and efficacy of AMX0035 (Amylyx Pharmaceuticals), an investigational agent for patients with amyotrophic lateral sclerosis (ALS), according to an announcement.¹

PHOENIX will span across approximately 65 sites in Europe and the US and plans to enroll 600 participants with clinically definite or clinically probable ALS within 24 hours from symptom onset. This differs from the previously completed phase 2/3 CENTAUR trial (NCT03127514), which included those with definite ALS diagnosis within 18 months of symptom onset.

"Given the results from CENTAUR, it is especially important that we advance the scientific understanding of ALS and continue investigating AMX0035 for the hundreds of thousands of people living with the disease worldwide," Leonard H. van den Berg, MD, PhD, professor of neurology, UMC Utrect, and chairman, Treatment Research Initiative to Cure ALS (TRICALS), said in a statement.¹ "We’re looking forward to collaborating on the phase 3 PHOENIX study with NEALS [Northeast ALS Consortium] as it will take a global and unified effort to make promising advances for patients and their families."

Over a 48-week period, investigators will assess the primary outcome of change on ALS Functional Rating Scale-Revised (ALSFRS-R) scale and survival. This randomized, placebo-controlled trial will also assess secondary efficacy outcomes such as change in slow vital capacity, measured both at home with a self-administered spirometer to support virtual data collection and at clinical sites, serial assessments of patient-reported outcomes, ventilation-free survival rates, and others.

READ MORE: CNM-Au8 Shows Efficacy Signals for ALS Despite Failing to Reach Primary End Point

The news comes less than a week after the company submitted a new drug application (NDA) to the FDA for AMX0035 for ALS. Amylyx’s hope is that the findings from PHOENIX will build upon the compelling findings from CENTAUR, which were the basis for the NDA.

In CENTAUR, participants were randomized 2:1 to AMX0035 (3-p PB and 1-g TURSO per sachet) or matching placebo, administered twice daily by mouth or feeding tube for a planned duration of 24 weeks. During the placebo-controlled phase, investigators documented a 44% lower risk of death for those on study drug compared with placebo (HR, 0.56 [95% CI, 0.34-0.92).²

"ALS is a relentlessly progressive disease with limited treatment options, which means advancements are critical for those living with the disease and their families," Sabrina Paganoni, MD, PhD, principal investigator of the CENTAUR study, investigator, Healey & AMG Center for ALS, Mass General, said in a statement.¹ "I’m enthusiastic about the opportunity to conduct a trial of this size and scope within the NEALS network of trial-ready research centers primarily based in North America, in partnership with TRICALS in Europe, as we continue to evaluate AMX0035 as a potential new therapeutic."

Additional data from CENTAUR indicated that AMX0035 met its primary efficacy end point, with a reported ALSFRS-R score of 2.32 points higher than placebo (P = .03) over 24 weeks. There was also a 2.92-point higher mean ALSFRS-R score for the AMX0035 group (P = .01) and a –1.24 points per month change in total ALSFRS-R score compared to –1.66 points per month with placebo (difference, 0.42 points per month [95% CI, 0.03-0.81]; P = .03).²

NeurologyLive recently caught up with Paganoni to discuss the parameters of the PHOENIX study and how it was influenced by CENTAUR. Watch below as she provides commentary on the notable features of the study, including top primary and secondary end points being observed.

REFERENCES

1. Amylyx Pharmaceuticals announces participants dosed in the global phase 3 PHOENIX study of AMX0035 in ALS. News release. Amylyx Pharmaceuticals. November 4, 2021. Accessed November 5, 2021. hsttps://www.businesswire.com/news/home/20211104005663/en/Amylyx-Pharmaceuticals-Announces-Participants-Dosed-in-the-Global-Phase-3-PHOENIX-Study-of-AMX0035-in-ALS

2. Paganoni S, Hendrix S, Dickson SP, et al. Long‐Term Survival of Participants in the CENTAUR Trial of Sodium Phenylbutyrate‐Taurursodiol in ALS. Muscle Nerve. 2021;63(1):31-39. doi: 10.1002/mus.27091.