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Sodium phenylbutyrate/ursodoxicoltaurine

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Sodium phenylbutyrate/ursodoxicoltaurine
Combination of
Sodium phenylbutyratePan-histone deacetylase inhibitor
Ursodoxicoltaurinebile acid
Clinical data
Trade namesAlbrioza, Relyvrio
Other namesAMX0035
Routes of
administration		By mouth
ATC code
  • None
Legal status
Legal status
Identifiers
KEGG

Sodium phenylbutyrate/ursodoxicoltaurine, also known as sodium phenylbutyrate/taurursodiol and sold under the brand name Albrioza among others, is a fixed-dose combination medication used for the treatment of amyotrophic lateral sclerosis (ALS).[2][4][6] It contains sodium phenylbutyrate and ursodoxicoltaurine (taurursodiol).[2]

The most common adverse reactions experienced with sodium phenylbutyrate/ursodoxicoltaurine include diarrhea, abdominal pain, nausea and upper respiratory tract infection.[7]

Sodium phenylbutyrate/ursodoxicoltaurine acts by blocking cell death pathways in mitochondria and in the endoplasmic reticulum.[6] Sodium phenylbutyrate is a chemical chaperone that helps proteins maintain their normal conformation, preventing aggregation that may lead to cell death.[6] Ursodoxicoltaurine improves mitochondrial energy production.[6]

The combination was approved for medical use in Canada as Albrioza, in June 2022,[1][2][8] and in the United States, as Relyvrio, in September 2022.[5][9][7]

Medical uses

Sodium phenylbutyrate/ursodoxicoltaurine is indicated for the treatment of amyotrophic lateral sclerosis (ALS).[2][4][5]

History

In a phase II/III clinical trial, CENTAUR, for ALS sodium phenylbutyrate/ursodoxicoltaurine (AMX0035) showed increased survival times.[10][11][12][13][14]

A phase II trial for Alzheimer's disease, PEGASUS, confirmed the safety and tolerability of sodium phenylbutyrate/ursodoxicoltaurine.[15]

The efficacy of sodium phenylbutyrate/ursodoxicoltaurine for the treatment of ALS was demonstrated in a 24-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study.[7][16] In the trial, 137 adult participants with ALS were randomized to receive either sodium phenylbutyrate/ursodoxicoltaurine or placebo.[7] The participants treated with sodium phenylbutyrate/ursodoxicoltaurine experienced a slower rate of decline on a clinical assessment of daily functioning compared to those receiving a placebo.[7] Additionally, longer overall survival was observed in a post hoc, long-term analysis of participants who originally received sodium phenylbutyrate/ursodoxicoltaurine versus those who originally received placebo.[7]

The US Food and Drug Administration (FDA) granted the application for the combination priority review and orphan drug designations.[7] The FDA granted the approval of Relyvrio to Amylyx Pharmaceuticals Inc.[7]

Society and culture

In the United States, healthcare insurer Cigna decided in 2023 to reverse its prior decision to cover the cost of the medication for all ALS patients, opting instead to cover "patients who meet certain clinical criteria", arguing that the drug is "experimental, investigational or unproven".[17]

Controversies

The FDA approval is controversial because of the small size of the trial. The FDA Peripheral and Central Nervous System Drugs Advisory Committee voted not to recommend approval, and then in an unusual second vote recommended approval.[18][19]

Research

It is being studied as a treatment for Alzheimer's disease[20][21] and Wolfram syndrome.[22]

References

  1. ^ a b "Qualifying notice for Albrioza". Health Canada. 13 June 2022. Archived from the original on 14 June 2022. Retrieved 13 June 2022.
  2. ^ a b c d e "Albrioza monograph" (PDF). 1 June 2022. Archived (PDF) from the original on 14 June 2022. Retrieved 14 June 2022.
  3. ^ "Summary Basis of Decision (SBD) for Albrioza". Health Canada. 23 October 2014. Retrieved 24 January 2023.
  4. ^ a b c "Relyvrio- sodium phenylbutyrate/taurursodiol powder, for suspension". DailyMed. 30 September 2022. Retrieved 16 October 2022.
  5. ^ a b c "Drug Approval Package: Relyvrio". U.S. Food and Drug Administration (FDA). 27 October 2022. Retrieved 18 November 2022.
  6. ^ a b c d "AMX0035". alsnewstoday. Archived from the original on 28 May 2021. Retrieved 15 June 2021.
  7. ^ a b c d e f g h "FDA Approves New Treatment Option for Patients with ALS". U.S. Food and Drug Administration (FDA) (Press release). 29 September 2022. Archived from the original on 29 September 2022. Retrieved 29 September 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  8. ^ "Amylyx Pharmaceuticals Announces Health Canada Approval of Albrioza for the Treatment of ALS" (Press release). Amylyx. 13 June 2022. Archived from the original on 14 June 2022. Retrieved 13 June 2022.
  9. ^ "Amylyx Pharmaceuticals Announces FDA Approval of Relyvrio for the Treatment of ALS". Amylyx (Press release). 29 September 2022. Archived from the original on 29 September 2022. Retrieved 29 September 2022.
  10. ^ Paganoni S, Macklin EA, Hendrix S, Berry JD, Elliott MA, Maiser S, et al. (September 2020). "Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis". The New England Journal of Medicine. 383 (10): 919–930. doi:10.1056/NEJMoa1916945. PMC 9134321. PMID 32877582.
  11. ^ Paganoni S, Hendrix S, Dickson SP, Knowlton N, Macklin EA, Berry JD, et al. (January 2021). "Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis". Muscle & Nerve. 63 (1): 31–39. doi:10.1002/mus.27091. PMC 7820979. PMID 33063909.
  12. ^ "Novel ALS Drug Continues to Show Survival Benefit". medpagetoday.com. 19 April 2021. Archived from the original on 19 May 2021. Retrieved 15 June 2021.
  13. ^ Paganoni S, Hendrix S, Dickson S, Knowlton N, Macklin E, Cohen J, et al. (13 April 2021). "Long-Term Survival of Participants in the CENTAUR Trial of AMX0035 for ALS (4550)". Neurology. 96 (15 Supplement). Archived from the original on 13 August 2021. Retrieved 15 June 2021.
  14. ^ "Long-term survival outcomes of AMX0035 for ALS". 22 April 2021. Archived from the original on 14 June 2022. Retrieved 15 June 2021.
  15. ^ "AMX0035 Meets Primary Safety and Tolerability End Point in Alzheimer Disease". Neurology live. Archived from the original on 21 November 2021. Retrieved 9 April 2022.
  16. ^ "AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS) (CENTAUR)". ClinicalTrials.gov. 25 April 2017. Archived from the original on 23 September 2022. Retrieved 29 September 2022.
  17. ^ Bell, Jacob (7 February 2023). "Cigna restricts coverage of new ALS drug, deepening fears about access". BiopharmaDive. Archived from the original on 8 February 2023. Retrieved 11 February 2023.
  18. ^ "ALS drug's approval draws cheers from patients, questions from skeptics". NPR. 30 September 2022. Archived from the original on 1 October 2022. Retrieved 30 September 2022.
  19. ^ Howard, Jacqueline (29 September 2022). "ALS drug gets FDA approval despite uncertainty about effectiveness". CNN. Archived from the original on 29 September 2022. Retrieved 30 September 2022.
  20. ^ "AMX0035 to Treat Alzheimer's Disease". alzheimers.gov. Archived from the original on 14 June 2022. Retrieved 15 June 2021.
  21. ^ "AMX0035". alzforum.org. Archived from the original on 13 June 2021. Retrieved 15 June 2021.
  22. ^ "Amylyx Pipeline". amylyx.com. Archived from the original on 24 June 2021. Retrieved 15 June 2021. We are currently exploring the potential of AMX0035 as a treatment option for ALS, Alzheimer's disease and Wolfram syndrome
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