Sodium phenylbutyrate/ursodoxicoltaurine

Last updated

Sodium phenylbutyrate/ursodoxicoltaurine
Combination of
Sodium phenylbutyrate Pan-histone deacetylase inhibitor
Ursodoxicoltaurine bile acid
Clinical data
Trade names Albrioza, Relyvrio
Other namesAMX0035
AHFS/Drugs.com Multum Consumer Information
MedlinePlus a623014
License data
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 names Albrioza and Relyvrio, 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]

Contents

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 apoptotic pathways in the 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] The European Union's drug regulators refused to approve it, citing concerns about effectiveness. [10] In April 2024, the manufacturer announced that it is withdrawing the medication from the US and Canadian markets, due to it failing a key phase III clinical trial. [11]

Medical uses

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

History

In the Phase II/III CENTAUR clinical trial, sodium phenylbutyrate/ursodoxicoltaurine (AMX0035) increased survival times for ALS patients. [12] [13] [14] [15] [16] The Phase II PEGASUS clinical trial found that the drug was safe and tolerated by patients with Alzheimer's disease. [17]

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] [18] Compared to members of the 137-adult cohort that received a placebo medication, those randomly assigned to treatment with sodium phenylbutyrate/ursodoxicoltaurine showed a slower rate of declining daily functioning and longer overall survival. [7]

In September 2022, the United States Food and Drug Administration (FDA) approved Amylyx Pharmaceuticals' application for Relyvrio's approval under the priority review and orphan drug programs. [7]

In March 2024, Amylyx Pharmaceuticals announced that its Phase III PHOENIX clinical trial of 664 American and European adults followed over 48 weeks showed no statistically significant difference in the functioning of ALS patients that were randomly assigned to treatment with Relyvrio, as compared to those receiving a placebo drug. [19]

Society and culture

The FDA Peripheral and Central Nervous System Drugs Advisory Committee voted not to recommend approval, and then in an unusual second vote recommended approval. [20] [21]

In April 2024, after a disappointing phase III trial of the medication failed to produce significant differences versus a placebo, [22] Amylyx announced they would begin the process of withdrawing Albrioza and Relyviro from the North American market. [11] [23]

Economics

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". [24]

Following the earlier announcement of plans to potentially withdraw the medication, the Institute for Clinical and Economic Review criticized the company for pricing the drug at $158,000 per year of treatment, given the uncertainty. [25]

Research

It is being studied as a treatment for Wolfram syndrome and progressive supranuclear palsy, despite the withdrawal of North American marketing authorization for amyotrophic lateral sclerosis (ALS). [11]

Related Research Articles

<span class="mw-page-title-main">Biogen</span> Pharmaceutical company

Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, United States specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide. Biogen operates in Argentina, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Mexico, Netherlands, Poland, Sweden, and Switzerland.

Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-mRNA, direct steric blockage, and exon content modulation through splicing site binding on pre-mRNA. Several ASOs have been approved in the United States, the European Union, and elsewhere.

<span class="mw-page-title-main">Investigational New Drug</span> USFDA program and prodecures

The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug across state lines before a marketing application for the drug has been approved. Regulations are primarily at 21 CFR 312. Similar procedures are followed in the European Union, Japan, and Canada.

<span class="mw-page-title-main">Pyrimethamine</span> Medication

Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin to treat the parasitic diseases toxoplasmosis and cystoisosporiasis. It is also used with dapsone as a second-line option to prevent Pneumocystis jiroveci pneumonia in people with HIV/AIDS. It was previously used for malaria but is no longer recommended due to resistance. Pyrimethamine is taken by mouth.

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, cytokine release syndrome, COVID‑19, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

Mecasermin rinfabate, also known as rhIGF-1/rhIGFBP-3, is a drug consisting of recombinant human insulin-like growth factor 1 (IGF-1) and recombinant human insulin-like growth factor binding protein-3 (IGFBP-3) which is used for the treatment of amyotrophic lateral sclerosis.

<span class="mw-page-title-main">ALS Association</span>

The ALS Association is an American nonprofit organization that funds global amyotrophic lateral sclerosis (ALS) research, provides care services and programs to people affected by ALS through its nationwide network of clinical care centers, and works with ALS advocates around the country for state and federal policies that serve people living with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.

<span class="mw-page-title-main">ALS</span> Rare neurodegenerative disease

Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease in the United States, is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset or bulbar-onset.

<span class="mw-page-title-main">Edaravone</span> Chemical compound

Edaravone, sold under the brand name Radicava among others, is a medication used to treat stroke and amyotrophic lateral sclerosis (ALS). It is given by intravenous infusion and by mouth.

Dextromethorphan/quinidine, sold under the brand name Nuedexta, is a fixed-dose combination medication for the treatment of pseudobulbar affect (PBA). It contains dextromethorphan (DXM) and the class I antiarrhythmic agent quinidine.

<span class="mw-page-title-main">Abacavir/dolutegravir/lamivudine</span> Combination medication for HIV

Abacavir/dolutegravir/lamivudine, sold under the brand name Triumeq among others, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It is a combination of three medications with different and complementary mechanisms of action: abacavir, dolutegravir and lamivudine.

<span class="mw-page-title-main">Omaveloxolone</span> Medication

Omaveloxolone, sold under the brand name Skyclarys, is a medication used for the treatment of Friedreich's ataxia. It is taken by mouth.

Genervon Biopharmaceuticals is a pharmaceutical company based in Pasadena, CA, focused on creating drugs for diseases of the central human nervous system. It is best known for its experimental drug, GM604, which seeks to treat Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.

<span class="mw-page-title-main">Erdafitinib</span> Chemical compound

Erdafitinib, sold under the brand name Balversa, is an anti-cancer medication. It is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) used for the treatment of cancer. FGFRs are a subset of tyrosine kinases which are unregulated in some tumors and influence tumor cell differentiation, proliferation, angiogenesis, and cell survival. Astex Pharmaceuticals discovered the drug and licensed it to Janssen Pharmaceuticals for further development.

Research on amyotrophic lateral sclerosis (ALS) has focused on animal models of the disease, its mechanisms, ways to diagnose and track it, and treatments.

Efgartigimod alfa, sold under the brand name Vyvgart, is a medication used to treat myasthenia gravis. Efgartigimod alfa is a neonatal Fc receptor blocker and is a new class of medication. It is an antibody fragment that binds to the neonatal Fc receptor (FcRn), preventing FcRn from recycling immunoglobulin G (IgG) back into the blood. The medication causes a reduction in overall levels of IgG, including the abnormal acetylcholine receptor (AChR) antibodies that are present in myasthenia gravis. It is also available coformulated with hyaluronidase.

<span class="mw-page-title-main">Brian Wallach</span> American advocate

Brian Wallach is an American businessman, lawyer, and amyotrophic lateral sclerosis (ALS) research and patient advocate. He became known for his activism after being diagnosed with ALS in 2017. Since then, Wallach has founded a nonprofit, I AM ALS, and a telemedicine company, Synapticure.

Amylyx Pharmaceuticals, Inc is a biopharmaceutical company headquartered in Cambridge, Massachusetts. Amylyx is best known for AMX0035, an experimental therapy for amyotrophic lateral sclerosis. AMX0035 was approved for medical use in Canada as Albrioza, in June 2022, and in the United States, as Relyvrio, in September 2022. It was withdrawn in April, 2024.

Bexagliflozin, sold under the brand name Brenzavvy, is an antidiabetic medication used to improve glycemic control in adults with type 2 diabetes. It is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that is taken by mouth.

<span class="mw-page-title-main">Tofersen</span> Medication

Tofersen, sold under the brand name Qalsody, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS). Tofersen is an antisense oligonucleotide that targets the production of superoxide dismutase 1, an enzyme whose mutant form is commonly associated with ALS. It is administered as an intrathecal injection.

References

  1. 1 2 "Qualifying notice for Albrioza". Health Canada. 13 June 2022. Archived from the original on 14 June 2022. Retrieved 13 June 2022.
  2. 1 2 3 4 5 "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. Archived from the original on 24 January 2023. Retrieved 24 January 2023.
  4. 1 2 3 "Relyvrio- sodium phenylbutyrate/taurursodiol powder, for suspension". DailyMed. 30 September 2022. Archived from the original on 16 October 2022. Retrieved 16 October 2022.
  5. 1 2 3 "Drug Approval Package: Relyvrio". U.S. Food and Drug Administration (FDA). 27 October 2022. Archived from the original on 18 November 2022. Retrieved 18 November 2022.
  6. 1 2 3 4 "AMX0035". alsnewstoday. Archived from the original on 28 May 2021. Retrieved 15 June 2021.
  7. 1 2 3 4 5 "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.PD-icon.svg 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. ↑ "Amylyx's ALS drug knocked back again in Europe". BioPharma Dive. Archived from the original on 19 January 2024. Retrieved 12 February 2024.
  11. 1 2 3 "Amylyx Pharmaceuticals Announces Formal Intention to Remove Relyvrio/Albrioza from the Market; Provides Updates on Access to Therapy, Pipeline, Corporate Restructuring, and Strategy". Amylyx Pharmaceuticals. 4 April 2024. Archived from the original on 4 April 2024. Retrieved 5 April 2024– via Business Wire.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ "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.
  15. ↑ 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). doi:10.1212/WNL.96.15_supplement.4550. S2CID   266100302. Archived from the original on 13 August 2021. Retrieved 15 June 2021.
  16. ↑ "Long-term survival outcomes of AMX0035 for ALS". 22 April 2021. Archived from the original on 14 June 2022. Retrieved 15 June 2021.
  17. ↑ "AMX0035 Meets Primary Safety and Tolerability End Point in Alzheimer Disease". Neurology live. 17 November 2021. Archived from the original on 21 November 2021. Retrieved 9 April 2022.
  18. ↑ "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.
  19. ↑ Belluck P (8 March 2024). "A.L.S. Drug Relyvrio Fails Clinical Trial and May Be Withdrawn From the Market". The New York Times . ISSN   0362-4331. Archived from the original on 9 March 2024. Retrieved 9 March 2024.
  20. ↑ "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.
  21. ↑ Howard J (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.
  22. ↑ "Amylyx Pharmaceuticals Announces Topline Results From Global Phase 3 PHOENIX Trial of AMX0035 in ALS". 8 March 2024. Archived from the original on 8 March 2024.
  23. ↑ "Dear health care professional letter: Albrioza". Health Canada . 20 June 2024. Retrieved 21 June 2024.
  24. ↑ Bell J (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.
  25. ↑ Saltzman J (8 March 2024). "In Setback for ALS Patients, Cambridge Biotech's Drug Fails Clinical Trial, Could Be Withdrawn From Market". The Boston Globe . Archived from the original on 8 March 2024. Retrieved 9 March 2024.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.