Last updated: September 8, 2026
Sodium phenylbutyrate and taurursodiol were commercialized in the United States as Relyvrio, an oral treatment for amyotrophic lateral sclerosis (ALS) developed by Amylyx Pharmaceuticals. The product generated rapid revenue growth after FDA approval in September 2022, reaching approximately $381.6 million in 2023. Its commercial trajectory reversed after the Phase 3 PHOENIX trial failed to confirm clinical benefit. Amylyx announced withdrawal of Relyvrio from the market in April 2024, eliminating the product’s near-term revenue base and materially weakening the company’s commercial position (Amylyx Pharmaceuticals, 2024a; Amylyx Pharmaceuticals, 2024b).
What are sodium phenylbutyrate and taurursodiol?
Relyvrio combined two active ingredients:
| Component |
Pharmacologic role |
Commercial significance |
| Sodium phenylbutyrate |
Nitrogen-scavenging agent that can reduce ammonia formation and may affect cellular stress pathways |
Previously marketed in other formulations, including Buphenyl |
| Taurursodiol |
Bile acid derivative associated with mitochondrial and endoplasmic-reticulum stress mechanisms |
Used in the combination as a neuroprotective component |
| Combination product |
Oral powder for suspension or packets, administered daily |
Sold under the Relyvrio brand in the U.S. and Albrioza in Canada |
The product’s development thesis was that sodium phenylbutyrate and taurursodiol could reduce mitochondrial dysfunction and endoplasmic-reticulum stress in ALS motor neurons. The FDA approval relied primarily on results from the CENTAUR trial and its open-label extension, rather than on a definitive Phase 3 confirmatory outcome (Paganoni et al., 2020).
When did Relyvrio receive FDA approval and lose commercial exclusivity?
The FDA approved Relyvrio on September 29, 2022, for the treatment of ALS in adults. The approval was based on evidence that included the CENTAUR randomized trial, which reported a slower rate of functional decline but did not demonstrate a statistically significant overall-survival benefit in the primary analysis (U.S. Food and Drug Administration, 2022; Paganoni et al., 2020).
The principal milestones were:
| Date |
Event |
| 2019 |
CENTAUR trial results published |
| September 2022 |
FDA approved Relyvrio for ALS |
| 2022 |
U.S. commercial launch |
| 2023 |
Full-year revenue reached about $381.6 million |
| September 2023 |
PHOENIX Phase 3 data failed to confirm benefit |
| April 2024 |
Amylyx announced voluntary withdrawal from the U.S. and Canadian markets |
| 2024 onward |
Commercial sales ended, with limited transition access for certain patients |
Relyvrio did not lose exclusivity because of a conventional generic launch. Its commercial collapse resulted from a negative confirmatory trial and voluntary withdrawal.
What did the PHOENIX trial show?
The PHOENIX trial was a global Phase 3 study involving participants with ALS. It failed to meet its primary endpoint and did not replicate the clinical benefit observed in the earlier CENTAUR program. Amylyx stated that the results did not support continued commercial availability of Relyvrio (Amylyx Pharmaceuticals, 2024a).
The trial changed the product’s risk profile in four ways:
- Physicians lost a confirmatory efficacy basis for continued prescribing.
- Payers faced a weaker value proposition for a high-cost therapy.
- Amylyx lost the regulatory and commercial rationale for maintaining the product.
- The FDA-approved product became subject to withdrawal rather than ordinary lifecycle competition.
The failure also reduced the probability that Relyvrio could support additional indications, international expansion, or a durable franchise based on the same mechanism.
How much revenue did sodium phenylbutyrate and taurursodiol generate?
Relyvrio produced rapid first-year commercial growth. Amylyx reported approximately $381.6 million in 2023 net product revenue, compared with approximately $28 million in 2022, reflecting the September 2022 launch and the expansion of prescribing and reimbursement during 2023 (Amylyx Pharmaceuticals, 2024b).
| Fiscal year |
Approximate Relyvrio revenue |
Market interpretation |
| 2022 |
$28 million |
Partial launch year |
| 2023 |
$381.6 million |
Peak commercial year |
| 2024 |
Sharp decline after withdrawal |
Product discontinued commercially |
The 2023 revenue level reflected several factors:
- High unmet need in ALS.
- Limited disease-modifying treatment options.
- Orphan-drug positioning.
- Rapid physician adoption after FDA approval.
- A high annual U.S. list price reported at roughly $163,000.
- Availability through commercial insurance, Medicare, Medicaid, and patient-support programs.
The revenue concentration created substantial downside exposure. Once Amylyx withdrew the product, the company lost its primary commercial product almost immediately. The collapse was therefore more severe than a normal patent-cliff decline, in which sales typically erode over several years through generic substitution.
What is the current FDA regulatory status of Relyvrio?
Relyvrio is no longer commercially available in the United States following Amylyx’s voluntary withdrawal announcement in April 2024. Amylyx also announced withdrawal of Albrioza from Canada. The company established transition arrangements for certain existing patients while commercial distribution was wound down (Amylyx Pharmaceuticals, 2024a).
The regulatory status differs from a standard generic or label-expansion lifecycle:
| Regulatory issue |
Status |
| FDA approval |
Granted in September 2022 |
| Current commercial availability |
Withdrawn from the U.S. market |
| Confirmatory evidence |
PHOENIX failed to confirm benefit |
| New patient initiation |
No longer supported through ordinary commercial distribution |
| Biosimilar pathway |
Not applicable |
| Generic substitution |
Not the primary cause of product discontinuation |
A withdrawal from the market does not automatically mean that every regulatory protection ended on the same day. FDA approval, commercial distribution, orphan-drug exclusivity, patents, and state substitution rules are separate legal matters.
What patents protect sodium phenylbutyrate and taurursodiol?
The commercial protection for Relyvrio depended more heavily on regulatory exclusivity, orphan-disease positioning, pricing, and market access than on a clearly established composition-of-matter patent for either active ingredient.
Sodium phenylbutyrate was already known and marketed before the Relyvrio combination. Taurursodiol is also a known chemical entity. The principal intellectual-property strategy therefore focused on the combination, dosing regimen, therapeutic use, and formulation rather than new-molecule exclusivity.
Are there Orange Book patents for Relyvrio?
The FDA Orange Book is the relevant source for approved-product patent and exclusivity information. Public FDA labeling and approval materials identify Relyvrio as an oral combination product, but the commercial withdrawal reduced the practical importance of any remaining Orange Book-listed patent or regulatory exclusivity.
No major public Paragraph IV campaign became the principal driver of Relyvrio’s market loss. The product was withdrawn after clinical failure before a conventional generic-entry event became commercially decisive.
The relevant protection categories were:
| Protection category |
Relevance to Relyvrio |
| New chemical entity exclusivity |
Limited relevance because the active ingredients were known |
| Orphan-drug exclusivity |
Potentially important after approval for ALS |
| Combination patents |
Potential protection for sodium phenylbutyrate plus taurursodiol |
| Method-of-use patents |
Potential protection for treating ALS with the combination |
| Formulation patents |
Potential protection for powder, packet, dosing, or stability characteristics |
| Patent term extension |
Not a central commercial driver after withdrawal |
| Regulatory approval |
Lost practical value after confirmatory failure |
The absence of a meaningful generic launch does not establish that no patents existed. It indicates that regulatory withdrawal and clinical evidence dominated the competitive outcome.
Were there Paragraph IV challenges or patent litigation?
No major public Paragraph IV litigation appears to have determined Relyvrio’s market outcome through the 2024 withdrawal announcement. The product’s commercial decline resulted from the PHOENIX trial and Amylyx’s decision to withdraw, not from a court ruling invalidating a key patent.
Patent litigation risk was structurally lower than for a high-volume chronic drug because:
- The ALS population is relatively small.
- The commercial window was short.
- The product was withdrawn before a typical generic filing cycle could mature.
- Sodium phenylbutyrate was already available in other products, but the Relyvrio combination had its own regulatory and formulation profile.
- Generic manufacturers had limited incentive to invest in an abbreviated application after the branded product’s withdrawal.
Any remaining disputes over combination, formulation, or method-of-use patents would have had limited economic value after commercial sales ended.
What generic launch risks exist?
Relyvrio had a meaningful theoretical generic risk but a limited practical generic-launch opportunity.
Small-molecule generic risk
Because Relyvrio was an oral small-molecule combination, it was potentially exposed to an abbreviated new drug application under the FDA’s generic pathway. A generic developer could have targeted:
- The same active ingredients.
- The same dosage form.
- A therapeutically equivalent powder formulation.
- A labeling strategy limited to non-patent-protected uses.
The principal barriers were commercial rather than technical. A generic entrant would have faced uncertain demand after the confirmatory trial failed, a withdrawn branded product, and a narrow ALS patient population.
Biosimilar risk
Biosimilar risk is not applicable. Sodium phenylbutyrate and taurursodiol are small molecules, not biologic products. The relevant competitive pathway is generic substitution, not the Biologics Price Competition and Innovation Act pathway.
How strong was the Relyvrio patent estate?
The patent estate was commercially moderate before the PHOENIX failure and weak after withdrawal. The product lacked the strongest form of pharmaceutical protection, a new chemical entity patent with a long remaining term and broad exclusivity around a novel active ingredient.
Strengths
- Combination-specific development history.
- Orphan indication in ALS.
- Potential method-of-use claims.
- Potential formulation and dosing claims.
- Limited direct competition at launch.
- Strong physician and patient demand before confirmatory failure.
Weaknesses
- Known active ingredients.
- Potentially narrow claim scope around the combination.
- Limited ability to prevent use of the individual components in separate products.
- Dependence on clinical efficacy evidence.
- No sustained commercial market after voluntary withdrawal.
- Low expected return for generic litigation after the product left the market.
The key commercial lesson is that patent protection could not compensate for a failed confirmatory trial. In rare disease, regulatory and clinical durability can be more important than nominal patent term.
What licensing deals and strategic partnerships affected the product?
Amylyx was the principal developer and commercial sponsor of Relyvrio in the United States and Albrioza in Canada. The product’s market development relied primarily on Amylyx’s own commercialization, patient-support infrastructure, and regulatory strategy rather than a large multinational licensing transaction.
The company’s strategic value was concentrated in:
- The ALS indication.
- The CENTAUR clinical package.
- The Relyvrio brand.
- Commercial payer access.
- The potential for international approvals.
- Development of related neurodegenerative-disease programs.
The negative PHOENIX result impaired the value of each asset. It reduced the commercial rationale for licensing the product and weakened negotiating leverage for any regional or indication-specific transaction.
How did Relyvrio compare with competing ALS drugs?
Relyvrio competed in a market that included riluzole, edaravone, and other ALS development programs.
| Product |
Active ingredient |
Approval status and positioning |
Competitive implication |
| Relyvrio |
Sodium phenylbutyrate plus taurursodiol |
Approved in 2022; withdrawn after PHOENIX failure |
No longer a durable commercial competitor |
| Rilutek and generics |
Riluzole |
Longstanding ALS therapy |
Low-cost and established option |
| Radicava and Radicava ORS |
Edaravone |
FDA-approved intravenous and oral formulations |
Direct disease-modifying alternative |
| Tofersen |
Antisense oligonucleotide |
Approved for SOD1-mutation ALS under an accelerated pathway |
Genetically targeted niche therapy |
| Investigational therapies |
Multiple mechanisms |
Clinical-stage programs |
Potential future substitutes |
Relyvrio’s initial differentiation was its oral combination, broad ALS label, and perceived tolerability. Its competitive position deteriorated when PHOENIX failed to validate benefit. Edaravone retained a more durable regulatory and commercial position, while tofersen established a targeted model for genetically defined ALS.
What manufacturing and intellectual-property barriers existed?
Manufacturing barriers were relatively modest compared with biologics or complex cell therapies. The product was an oral powder combination, and its active ingredients were not novel biologic substances requiring proprietary cell lines or complex manufacturing platforms.
Potential technical barriers included:
- Consistent blending of two active ingredients.
- Dose uniformity in powder packets.
- Stability and moisture control.
- Taste and administration characteristics.
- Packaging requirements.
- Bioequivalence for the finished combination product.
These barriers could slow generic development but were unlikely to create a durable manufacturing moat. The commercial withdrawal removed much of the incentive to overcome them.
What is the financial outlook for Amylyx after Relyvrio?
Amylyx’s financial outlook changed from a commercial-growth profile to a restructuring and pipeline-dependent profile after 2024. The company had to replace a product that had generated hundreds of millions of dollars in annual revenue with earlier-stage assets and reduced operating infrastructure.
The main financial consequences were:
- Loss of recurring Relyvrio product revenue.
- Workforce reductions and commercial restructuring.
- Lower expected return on the company’s ALS infrastructure.
- Greater reliance on cash reserves and pipeline milestones.
- Reduced bargaining power in licensing transactions.
- Higher risk that future programs would require external capital or partners.
The company’s valuation after withdrawal was therefore driven less by Relyvrio’s historical sales and more by the probability of clinical success for replacement programs. The 2023 revenue peak should not be used as a forward run-rate.
Key Takeaways
- Relyvrio generated approximately $381.6 million in 2023 revenue after FDA approval in September 2022.
- The PHOENIX Phase 3 trial failed to confirm the product’s clinical benefit.
- Amylyx announced voluntary withdrawal from the U.S. and Canadian markets in April 2024.
- The product’s market failure was caused by clinical and regulatory developments, not a conventional generic launch.
- Biosimilar risk does not apply because the product is a small-molecule combination.
- Patent protection centered on combination, formulation, and method-of-use concepts rather than novel active-ingredient protection.
- The product’s strongest commercial protections were orphan-disease positioning, limited competition, and market access.
- Relyvrio’s withdrawal transformed Amylyx from a revenue-generating commercial company into a pipeline-dependent biotechnology company.
FAQs
Is sodium phenylbutyrate still available after Relyvrio withdrawal?
Sodium phenylbutyrate remains available in other approved products and formulations, including products used for urea-cycle disorders. Its availability is separate from the withdrawal of the sodium phenylbutyrate and taurursodiol combination.
Can a generic company still develop a Relyvrio equivalent?
A generic developer could theoretically pursue an equivalent combination, but the commercial opportunity is limited by Relyvrio’s withdrawal, the failed PHOENIX trial, and the small ALS population.
Did Relyvrio have orphan-drug exclusivity?
Relyvrio received orphan-drug treatment associated with its ALS indication. The practical value of that exclusivity declined sharply once Amylyx withdrew the product and the confirmatory clinical evidence failed.
Was Relyvrio approved under the FDA accelerated-approval pathway?
The FDA approved Relyvrio based on the clinical evidence available at the time, including the CENTAUR program. The subsequent PHOENIX trial was intended to provide additional confirmatory evidence and failed to demonstrate benefit.
What happened to Amylyx’s Relyvrio revenue after 2023?
Revenue declined sharply after the company announced withdrawal in 2024. The 2023 figure of approximately $381.6 million represented the product’s peak commercial year and is not a sustainable forward estimate.
References
Amylyx Pharmaceuticals, Inc. (2024a, April 4). Amylyx Pharmaceuticals announces voluntary withdrawal of AMX0035 from the U.S. and Canada. Company press release.
Amylyx Pharmaceuticals, Inc. (2024b). Annual report on Form 10-K for the fiscal year ended December 31, 2023. U.S. Securities and Exchange Commission.
Paganoni, S., Macklin, E. A., Hendrix, S., Berry, J. D., Elliott, M. A., Maiser, S., Karam, C., Caress, J. B., Owegi, M. A., Quick, A., Goetz, R., Cohen, J., Hesterlee, S. E., Appel, S. H., Sherman, A., Greenblatt, D. J., Harkins, A., Nahabedian, C., ... Cudkowicz, M. E. (2020). Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis. New England Journal of Medicine, 383(10), 919-930. https://doi.org/10.1056/NEJMoa1916945
U.S. Food and Drug Administration. (2022, September 29). FDA grants approval to drug for patients with ALS. FDA.
