FDA Approves an Oral Combination Drug for ALS After Two Advisory Meetings (2022)

On September 29, 2022, the U.S. Food and Drug Administration (FDA) approved a combination of two compounds, sodium phenylbutyrate and taurursodiol, taken by mouth as a powder stirred into water, to treat amyotrophic lateral sclerosis (ALS) in adults. The approval came after the FDA’s outside advisers on nervous-system drugs met twice that year to discuss the application, and it rested on a single 24-week clinical trial of 137 patients. A larger trial reported in 2024 did not meet its goals, and the FDA withdrew the approval on August 29, 2025, at the drug maker’s request. The disease itself is described on the site’s Amyotrophic Lateral Sclerosis (ALS) page.

This page reports what the FDA’s own documents say: the approval, the disease as the FDA describes it, how the drug was taken, the two advisory committee meetings, the trial evidence and who took part, the side effects reported, the timeline behind the application, what the approval did not do, the 2024 trial result and the 2025 withdrawal, its status as of October 18, 2026, and how it fits other FDA actions. No brand, company or trial name is used here; the drug is named by its generic ingredients.

Table of Contents

  1. What the FDA Approved on September 29, 2022
  2. ALS as the FDA Describes It
  3. The Drug and How It Was Taken
  4. Two Advisory Committee Meetings in 2022
  5. The Evidence: One 137-Patient Trial
  6. Who Took Part in the Trial
  7. Side Effects Reported in the Trial
  8. The Timeline Behind the Application
  9. What the Approval Did Not Do
  10. The 2024 Trial Result and the 2025 Withdrawal
  11. Dates and Legal Status as of October 18, 2026
  12. How It Fits Other FDA Actions
  13. Primary Documents
  14. Key Research Papers
  15. Connections
  16. Featured Videos

1. What the FDA Approved on September 29, 2022

The FDA’s Drug Trials Snapshot for the drug gives its “Original Approval date” as September 29, 2022, and states that it “is a drug that treats adult patients with amyotrophic lateral sclerosis (ALS).” The FDA’s 2025 Federal Register notice on the drug restates the action in formal terms: “On September 29, 2022, FDA approved NDA 216660 … (sodium phenylbutyrate and taurursodiol) for suspension, 3 g/packet and 1 g/packet, for the treatment of amyotrophic lateral sclerosis (ALS) in adults.”

An NDA, or new drug application, is the file a drug maker submits asking the FDA to approve a drug for sale in the United States; NDA 216660 is this drug’s application number. A Drug Trials Snapshot is a plain-language FDA summary of the clinical trials behind a drug’s first approval. The Snapshot itself carries a caution in the FDA’s words: “Do not rely on Snapshots to make decisions regarding medical care.”

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2. ALS as the FDA Describes It

The Snapshot describes ALS as “a rare disease that attacks and kills the nerve cells that control voluntary muscles.” Voluntary muscles, it explains, “produce movements such as chewing, walking, breathing, and talking.” The disease causes the nerves to lose the ability to activate specific muscles, “leading to muscle weakness and paralysis.” The FDA adds that ALS “is a progressive disease that worsens over time, and often leads to death within three to five years from when symptoms first appear.”

The history of the disease and of earlier treatment efforts is told on the site’s ALS: History and Discovery page.

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3. The Drug and How It Was Taken

The product combined two ingredients, sodium phenylbutyrate and taurursodiol, in one powder. The approved strengths were 3 g/packet and 1 g/packet, and the Federal Register notices for the advisory meetings describe it as a “powder for oral suspension,” meaning a powder mixed into liquid and swallowed.

According to the Snapshot, the drug was taken by mouth once daily for three weeks, after which “the dosage can be increased to twice a day.” It was taken “by combining one packet in 8 ounces of room temperature water and stirring vigorously,” before a snack or meal, and the Snapshot notes that it “can also be administered through a feeding tube.” The Snapshot describes taurursodiol as a bile acid.

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4. Two Advisory Committee Meetings in 2022

Before deciding, the FDA brought the application to its Peripheral and Central Nervous System Drugs Advisory Committee twice. An FDA advisory committee is a panel of outside experts; the Federal Register notices state that “The general function of the committee is to provide advice and recommendations to FDA on regulatory issues.” The FDA makes the final decision itself. Both meetings were open to the public, and for each the FDA opened a public docket, the official file on regulations.gov where documents and public comments are kept.

The approval followed three weeks after the second meeting. The FDA documents read for this page do not give the committee’s votes, and they are not reported here.

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5. The Evidence: One 137-Patient Trial

The Snapshot states that the FDA approved the drug “based on safety and efficacy data from a single clinical trial (Study 1) of 137 adult patients with ALS,” conducted at 25 sites in the United States. It describes the trial as “a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.” In plain terms: patients were assigned by chance to the drug or to a placebo (an inactive look-alike), two on the drug for every one on placebo (89 and 48), and neither the patients nor their doctors knew who was getting which.

The main measure was the ALS Functional Rating Scale-Revised (ALSFRS-R), a clinical score of daily functioning that falls as the disease progresses. The trial compared how fast that score fell from the start to week 24. The Snapshot reports:

The Snapshot also describes a later look at survival. In a post hoc analysis, meaning one planned after the trial ended rather than before it began, the vital status of 136 of the 137 patients was checked, and “A longer median overall survival was observed in patients originally randomized to [the drug] compared to those originally randomized to placebo.” The FDA attached a caution to this finding: “This exploratory analysis should be interpreted cautiously given the limitations of data collected outside of a controlled study, which may be subject to confounding.”

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6. Who Took Part in the Trial

The FDA’s demographic table for the trial’s 137 patients shows:

The Snapshot states that “The number of patients of races other than White was small; therefore, differences in how [the drug] worked among races could not be determined,” and that the small numbers and imbalances between subgroups limit what can be concluded about differences by sex and age.

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7. Side Effects Reported in the Trial

The Snapshot lists the most common adverse reactions as “diarrhea, abdominal pain, nausea, and upper respiratory tract infection.” Its table of reactions seen in more than 5% of treated patients, and at least 5 percentage points more often than on placebo, reads:

The FDA adds that gastrointestinal reactions “occurred throughout the study but were more frequent during the first three weeks of treatment,” and that abdominal pain was more common in patients older than 65. It also states that taurursodiol, a bile acid, “may cause worsening diarrhea in patients with disorders that interfere with bile acid circulation,” and that the FDA advised such patients to consult a specialist before taking the drug.

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8. The Timeline Behind the Application

A March 4, 2024 FDA notice, issued to help the U.S. Patent and Trademark Office decide on a patent-term extension (89 FR 15588), sets out the drug’s regulatory history as the FDA’s records show it:

The FDA counted a regulatory review period of 3,359 days: “3,023 days occurred during the testing phase of the regulatory review period, while 336 days occurred during the approval phase.” The notice explains that this determination “establishes the maximum potential length of a patent extension.”

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9. What the Approval Did Not Do

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10. The 2024 Trial Result and the 2025 Withdrawal

The FDA’s notice of August 29, 2025 (90 FR 42251; Docket No. FDA-2025-N-2654) sets out what happened after the approval:

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11. Dates and Legal Status as of October 18, 2026

Status as of October 18, 2026: approval withdrawn. The September 29, 2022 approval has been withdrawn since August 29, 2025. A check of the Federal Register through October 18, 2026 for FDA documents naming the drug’s ingredients found no later document that changes this; the other entries found are routine lists of product-specific guidances (2024) and the 2024 patent-term notice described above.

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12. How It Fits Other FDA Actions

The pattern of this action, an approval followed years later by withdrawal after a larger trial failed to confirm a benefit, also appears in the FDA’s 2023 withdrawal of the only drug for preventing preterm birth. Among other drug approvals for nervous-system diseases reported on the site are the 2023 traditional approval of lecanemab and the 2024 approval of donanemab for early Alzheimer’s disease.

Other 2022 drug actions are reported on their own pages: the May 2022 approval of tirzepatide for type 2 diabetes, the November 2022 approval of teplizumab to delay type 1 diabetes, the November 2022 approval of a fecal microbiota product for recurrent C. difficile infection and the January 2022 warning about dental problems with buprenorphine. All of the FDA’s 2022 actions covered on the site are listed on the FDA Actions of 2022 hub.

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13. Primary Documents

  1. U.S. Food and Drug Administration. Drug Trials Snapshot for sodium phenylbutyrate and taurursodiol. Original approval date September 29, 2022; content current as of December 12, 2023. No Federal Register docket. Found under Drug Trials Snapshots on fda.gov; its web address carries the brand name and is not linked here.
  2. Food and Drug Administration, HHS (2022). Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments. Notice. Federal Register 87 FR 9064–9066, February 17, 2022. Meeting March 30, 2022. Docket No. FDA-2018-N-0410 — FR Doc. 2022-03430
  3. Food and Drug Administration, HHS (2022). Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments. Notice. Federal Register 87 FR 47432–47433, August 3, 2022. Meeting September 7, 2022. Docket No. FDA-2022-N-1436 — FR Doc. 2022-16570
  4. Food and Drug Administration, HHS (2024). Determination of Regulatory Review Period for Purposes of Patent Extension (sodium phenylbutyrate and taurursodiol). Notice. Federal Register 89 FR 15588, March 4, 2024. Docket Nos. FDA-2023-E-2603 to FDA-2023-E-2606 — FR Doc. 2024-04480
  5. Food and Drug Administration, HHS (2025). Withdrawal of Approval of New Drug Application for sodium phenylbutyrate and taurursodiol for suspension, 3 gram/packet and 1 gram/packet. Notice. Federal Register 90 FR 42251, August 29, 2025. Docket No. FDA-2025-N-2654 — FR Doc. 2025-16646
  6. Public docket FDA-2018-N-0410 — regulations.gov FDA-2018-N-0410
  7. Public docket FDA-2022-N-1436 — regulations.gov FDA-2022-N-1436

The Federal Register titles of documents 4 and 5 name the brand and, for document 5, the drug maker; they are given here by their generic content.

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Key Research Papers

  1. Paganoni S, Macklin EA, Hendrix S, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, et al. (2020). Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis. The New England Journal of Medicine 383(10):919-930 — PubMed PMID: 32877582
  2. Paganoni S, Hendrix S, Dickson SP, Knowlton N, Macklin EA, Berry JD, Elliott MA, Maiser S, et al. (2021). Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. Muscle & Nerve 63(1):31-39 — PubMed PMID: 33063909
  3. Paganoni S, Hendrix S, Dickson SP, Knowlton N, Berry JD, Elliott MA, Maiser S, Karam C, et al. (2022). Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial. Journal of Neurology, Neurosurgery, and Psychiatry 93(8):871-875 — PubMed PMID: 35577511
  4. Sun Y, Li X, Bedlack R (2023). An evaluation of the combination of sodium phenylbutyrate and taurursodiol for the treatment of amyotrophic lateral sclerosis. Expert Review of Neurotherapeutics 23(1):1-7 — PubMed PMID: 36705941
  5. Calcagno N, Scirocco E, Clampffer E, Addy G, Morgan S, Parikh N, Neel DV, Scalia J, et al. (2025). Real-World Clinical Experience With Sodium Phenylbutyrate and Taurursodiol at a Single Amyotrophic Lateral Sclerosis Center in the United States. European Journal of Neurology 32(9):e70360 — PubMed PMID: 40965373
  6. Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, Sobue G (2022). Amyotrophic lateral sclerosis. The Lancet 400(10360):1363-1380 — PubMed PMID: 36116464
  7. Brown RH, Al-Chalabi A (2017). Amyotrophic Lateral Sclerosis. The New England Journal of Medicine 377(2):162-172 — PubMed PMID: 28700839

The first paper reports the 24-week randomized trial of 137 patients described by the FDA’s Snapshot; the second and third report the trial investigators’ longer-term survival and hospitalisation follow-up. The fourth is a review of the combination published after the approval, and the fifth describes clinical experience with the drug at one U.S. ALS center. The last two are general reviews of ALS.

PubMed Topic Searches

  1. PubMed: sodium phenylbutyrate and taurursodiol in ALS
  2. PubMed: ALS treatment clinical trials
  3. PubMed: ALSFRS-R as a trial endpoint

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Connections

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