The Food and Drug Administration (FDA) has approved Relyvrio (sodium phenylbutyrate and taurursodiol) for the treatment of amyotrophic lateral sclerosis (ALS) in adults.

Relyvrio is an oral, fixed-dose coformulation of sodium phenylbutyrate and taurursodiol, also known as ursodoxicoltaurine. By targeting the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS, Relyvrio is expected to reduce neuronal death and dysfunction.

The approval was supported by data from the phase 2 CENTAUR trial (ClinicalTrials.gov Identifier: NCT03127514), a double-blind, placebo-controlled, parallel-group study that evaluated Relyvrio in adult patients with ALS (N=137). Patients were randomly assigned to receive Relyvrio (n=89) or placebo (n=48) for 24 weeks (intent-to-treat [ITT] population); baseline disease characteristics were reported to be comparable between the 2 groups.  

The primary endpoint of the study was a comparison of the rate of reduction in the ALS Functional Rating Scale-Revised (ALSFRS-R) total scores from baseline to week 24 in the mITT population. The ALSFRS-R scale consists of 12 questions that evaluate fine motor, gross motor, bulbar, and respiratory function of patients with ALS.

Results showed a statistically significant difference in the rate of reduction in the ALSFRS-R total score from baseline to week 24 in the Relyvrio group compared with the placebo group (treatment difference, 2.32 points [95% CI, 0.18-4.47]; P =.034).

Findings from a post hoc, long-term survival analysis also demonstrated longer median overall survival in patients who were treated with Relyvrio vs those who received placebo.  It should be noted that this exploratory analysis should be interpreted cautiously given the limitations of data collected outside of a controlled study.

The most common adverse reactions reported with Relyvrio were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea. Additionally, the product has a high salt content so the amount of daily sodium intake should be considered in patients sensitive to high salt intake.

Relyvrio is supplied in single-dose packets containing 3g of sodium phenylbutyrate and 1g of taurursodiol. The contents of the packet should be mixed with 8 ounces of room temperature water and administered (before a snack or meal) either orally or via feeding tube within 1 hour of preparation. The recommended initial dosage of Relyvrio for oral suspension is 1 packet daily for the first 3 weeks. After 3 weeks, the dosage is increased to 1 packet twice daily (maintenance dosage).

“Our priority now is to ensure that adults living with ALS in the US whose doctors have prescribed Relyvrio can access it as quickly as possible,” said Margaret Olinger, Global Head of Commercial and Chief Commercial Officer of Amylyx. “Physicians will be able to prescribe immediately, and we anticipate specialty pharmacies will be able to start to fill prescriptions and ship Relyvrio to people with ALS in the next 4 to 6 weeks.”

References

  1. Amylyx Pharmaceuticals announces FDA approval of Relyvrio™ for the treatment of ALS. News release. September 29, 2022. Accessed September 30, 2022. https://www.businesswire.com/news/home/20220929005962/en/Amylyx-Pharmaceuticals-Announces-FDA-Approval-of-RELYVRIO%E2%84%A2-for-the-Treatment-of-ALS
  2. Relyvrio. Package insert. Amylyx Pharmaceuticals; 2022. Accessed September 30, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/216660s000lbledt.pdf