Palatability Strategies Show Promise for Addressing AMX0035 Taste Concerns Among Patients With ALS

Nicole Shuckett, RD, MSc

New data from a small study utilizing semistructured, qualitative interviews with patients with amyotrophic lateral sclerosis (ALS) and health care professionals suggest that there are a variety of strategies that can be implemented in real-world clinical care to overcome any palatability issues faced by patients treated with AMX0035 (Relyvrio; Amylyx Pharmaceuticals), a recently approved therapy for ALS.¹

Since its approval earlier in 2022 in Canada, and its subsequent approval in the United States, some patients with ALS have expressed palatability and taste issues with the therapy, which is a coformulation of sodium phenylbutyrate and taurursodiol/ursodoxicoltaurine. The data were presented at the 2022 Northeast Amyotrophic Lateral Sclerosis (NEALS) Meeting, held November 1-3, in Clearwater Beach, Florida. Investigator Nicole Shuckett, RD, MSc, a private practice dietitian in Toronto, Ontario, and colleagues noted that “coformulation can have a bitter taste to some people living with ALS, which may compromise adherence and, consequently, treatment effectiveness.”

The group pointed to the Canadian product monograph’s examples as the key aspects of reducing any possible negative downstream effects of the bitter taste. Ultimately, the 3 suggested tactics were as follows: 1. Use mint-flavored mouth strips or mouth spray immediately before or after administration; 2. Eat a snack or a meal, eat honey, or drink milk after administration; and 3. Avoid drinking fruit juice at the same time of administration.

In total, the group’s work included 6 patients with ALS, 3 clinic nurses/coordinators, and 1 neurologist specializing in ALS care. All 6 patients (100%) reported utilizing at least 1 of the strategies, with none of them reporting a discontinuation of treatment owing to taste. Comparatively, among 217 individuals exposed to AMX0035 via the Health Canada Special Access Program, 3.7% (n = 8) reported discontinuation for this reason.

Notably, Shuckett et al wrote that “[people with ALS] may have altered taste perception for a multitude of reasons, including degeneration of the solitary nuclei, impairment of the cranial nerves innervating the taste buds, medications, and genetics,” and that “in particular, differential disease effects on the cranial nerves may preserve or potentiate output from gustatory cells located in the circumvallate papillae that perceive bitter taste.”

Additional thematic administration strategies that Shuckett and colleagues identified from their survey data were mixing the medication with a milk frother, shaking the suspension in a jar, drinking the suspension in a single gulp, or pinching the nose when consuming the suspension. As for taste-enhancing techniques, those surveyed reported trying Nature’s Wild Berry, eating a variety of strong-tasting foods, brushing one’s teeth, and avoiding citrus, all immediately following administration.

Although the group noted that “further studies are needed to substantiate and enrich these preliminary results,” the finding suggest that these strategies might be implemented to “manage taste expectations and enhance the palatability” of AMX0035.

AMX0035 was approved by the FDA in late September 2022, making it the third such drug approved for slowing disease progression in ALS in the United States. It joined riluzole (Rilutek; Sanofi) and edaravone (Radicava; MT Pharma)—which received approvals in 1995 and 2017, respectively. AMX0035’s approval was based on the phase 2 CENTAUR study (NCT03127514)—and followed 2 meetings held by the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (AdComm) to discuss the findings.^2,3

All told, 137 patients were randomly assigned in CENTAUR to either AMX0035 (n = 89) or placebo (n = 48) and had rate of decline assessed through the ALS Functional Rating Scale-Revised (ALSFRS-R) over a 24-week treatment period. Throughout the study, most patients (77%) were receiving riluzole or edaravone at or before trial entry, with 28% of participants who received both. AMX0035 met its primary end point, with between group differences of 0.42 points per month on ALSFRS-R compared with placebo.⁴

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REFERENCES
1. Shuckett N, Wainwright S, Jayson T, Timmons J. Real-world Strategies to Enhance the Palatability of Coformulated Sodium Phenylbutyrate and Taurursodiol for the Treatment of Amyotrophic Lateral Sclerosis. Presented at: NEALS Annual Meeting; November 1-4, 2022; Clearwater Beach, FL and Virtual. Abstract 32.
2. Amylyx Pharmaceuticals announces FDA approval of Relyvrio for the treatment of ALS. News release. Amylyx Pharmaceuticals. September 29, 2022. Accessed November 1, 2022. https://www.amylyx.com/media/amylyx-pharmaceuticals-announces-fda-approval-of-relyvriotm-for-the-treatment-of-als
3. FDA. Peripheral and Central Nervous System Drugs Advisory Committee Meeting. March 30, 2022. Accessed November 1, 2022.
4. Paganoni S, Macklin EA, Hendrix S, et al. Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. N Engl J Med. 2020;383:919-930. doi:10.1056/NEJMoa19169