Relyvrio: A New FDA-Approved Treatment for Patients With ALS

On September 29, 2022, the FDA approved sodium phenylbutyrate and taurursodiol (Relyvrio) for the treatment of amyotrophic lateral sclerosis (ALS) in adults^1,2 based on promising data from a small phase 2 clinical trial (NCT03127514).³ Sodium phenylbutyrate and taurursodiol is designed to slow disease progression and can be given as monotherapy or in combination with other agents. The mechanism by which this medication exerts its therapeutic effects on patients with ALS is unknown. A large phase 3 study (NCT05021536) is ongoing to confirm the safety and efficacy of sodium phenylbutyrate and taurursodiol in this patient population.

Efficacy

The efficacy of sodium phenylbutyrate and taurursodiol for the treatment of ALS was demonstrated in a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in adult patients with ALS. A total of 137 patients were randomly assigned 2:1 to receive either sodium phenylbutyrate and taurursodiol (n = 89) or placebo (n = 48) for 24 weeks. The prespecified primary efficacy end point was a comparison of the rate of reduction in the revised ALS Functional Rating Scale (ALSFRS-R) total scores from baseline to week 24. The ALSFRS-R scale consists of 12 questions that evaluate the fine motor, gross motor, bulbar, and respiratory function of patients with ALS. Each item is scored from 0 to 4, with higher scores indicating higher functional ability. There was a statistically significant difference in the rate of reduction in the ALSFRS-R total score from baseline to week 24 in patients who received sodium phenylbutyrate and taurursodiol compared with patients who received placebo (P = .034).

Data demonstrated that patients with ALS treated with sodium phenylbutyrate and taurursodiol vs placebo had a slower rate of decline on a clinical assessment of daily functioning and longer median overall survival. Secondary outcomes were not significantly different between the 2 groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate and taurursodiol in patients living with ALS.

Safety

The medication contains taurursodiol, a bile acid, so in patients with disorders that interfere with bile acid circulation or alter concentrations, there may be an increased risk of worsening diarrhea. Bile acid–sequestering agents may interfere with the absorption of sodium phenylbutyrate and taurursodiol, and it is recommended to avoid concomitant use.

Each packet of sodium phenylbutyrate and taurursodiol contains 464 mg of sodium, so in patients sensitive to salt intake (eg, those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose and monitor for hypernatremia.

The most common adverse reactions (at least 15% and at least 5% greater than placebo) with sodium phenylbutyrate and taurursodiol were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment.

Dosing

The recommended initial dosage of sodium phenylbutyrate and taurursodiol for oral suspension is 1 packet (3-g sodium phenylbutyrate and 1-g taurursodiol) daily for the first 3 weeks. After 3 weeks, increase the dose to 1 packet twice daily.

To prepare a dose, empty the contents of 1 packet into 8 oz of room temperature water and stir vigorously to combine the mixture. Instruct to take orally or administer via feeding tube. Sodium phenylbutyrate and taurursodiol should be given before a snack or meal and within 1 hour of preparation. Any unused, reconstituted suspension should be discarded after 1 hour.

References

1. Relyvrio. Prescribing information.Amylyx Pharmaceuticals Inc; 2022.Accessed November 10, 2022. https://www.amylyx.com/document/RELYVRIO-US-Prescribing-Information.pdf

2. FDA approves first ALS treatment funded by Ice Bucket Challenge. News release. ALS Association. September 29, 2022. Accessed November 9, 2022. https://www.als.org/stories-news/fda-approves-first-als-treatment-funded-ice-bucket-challenge 

3. Paganoni S, Macklin EA, Hendrix S, et al. Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis. N Engl J Med.2020;383(10):919-930. doi:10.1056/NEJMoa1916945