List of Excipients in Branded Drug RELYVRIO

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Amylyx Pharmaceuticals Inc	RELYVRIO	sodium phenylbutyrate/taurursodiol	73063-035	ACACIA	2029-09-29
Amylyx Pharmaceuticals Inc	RELYVRIO	sodium phenylbutyrate/taurursodiol	73063-035	DEXTRATES	2029-09-29
Amylyx Pharmaceuticals Inc	RELYVRIO	sodium phenylbutyrate/taurursodiol	73063-035	MALTODEXTRIN	2029-09-29
Amylyx Pharmaceuticals Inc	RELYVRIO	sodium phenylbutyrate/taurursodiol	73063-035	MEDIUM-CHAIN TRIGLYCERIDES	2029-09-29
Amylyx Pharmaceuticals Inc	RELYVRIO	sodium phenylbutyrate/taurursodiol	73063-035	SILICON DIOXIDE	2029-09-29
Amylyx Pharmaceuticals Inc	RELYVRIO	sodium phenylbutyrate/taurursodiol	73063-035	SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	2029-09-29
Amylyx Pharmaceuticals Inc	RELYVRIO	sodium phenylbutyrate/taurursodiol	73063-035	SODIUM STEARYL FUMARATE	2029-09-29

Relyvrio Excipient Strategy and Commercial Opportunities

Last updated: August 9, 2026

Relyvrio was an oral powder combining sodium phenylbutyrate and taurursodiol for amyotrophic lateral sclerosis (ALS). Its commercial opportunity changed materially after Amylyx Pharmaceuticals reported negative Phase 3 PHOENIX results and announced withdrawal from the market in 2024. The strongest remaining opportunities are formulation redevelopment, authorized or generic supply, ex-US access, and excipient-enabled improvements for patients with dysphagia and enteral feeding requirements.

What is Relyvrio and how was it formulated?

Relyvrio, also known as AMX0035, contained two active ingredients:

Product characteristic	Relyvrio profile
Active ingredients	Sodium phenylbutyrate and taurursodiol
Strength per packet	3 g sodium phenylbutyrate plus 1 g taurursodiol
Administration	Powder mixed with approximately 8 ounces of water or juice
Typical dose	One packet twice daily
Dosage form	Oral powder for suspension
Therapeutic area	Amyotrophic lateral sclerosis
Sponsor	Amylyx Pharmaceuticals
FDA approval	September 2022
FDA pathway	New drug application 214457
Commercial status	Withdrawal announced in 2024 after negative PHOENIX results

The product design addressed several formulation constraints. Sodium phenylbutyrate has a strong taste and odor, while taurursodiol has limited water solubility. A dry powder allowed the two active ingredients to remain stable before use and avoided the shelf-life limitations of a ready-to-drink liquid.

The formulation also supported a relatively simple manufacturing process: weigh the two active ingredients, blend with selected excipients, fill into unit-dose packets, and package with moisture protection.

What excipients were used in Relyvrio?

Relyvrio’s US prescribing information identifies inactive ingredients, but the commercial value of the excipient system is better understood by function than by ingredient count. The formulation required excipients for powder flow, dispersibility, taste management, and product stability.[1]

Functional excipient requirements

The main excipient functions were:

1. Improving powder handling during blending and packet filling.
2. Promoting rapid dispersion after mixing with water or juice.
3. Managing the unpleasant taste associated with sodium phenylbutyrate.
4. Supporting chemical and physical stability in a moisture-sensitive unit-dose package.
5. Maintaining a reproducible dose despite the relatively high total powder mass.

The product did not depend on a sophisticated modified-release system. Its commercial differentiation came from combining two active ingredients in a convenient unit-dose powder, rather than from a complex delivery platform.

Why the excipient system matters

Sodium phenylbutyrate is used in other products and has known palatability problems. In an ALS population, taste and administration burden can directly affect adherence because many patients experience dysphagia, weakness, fatigue, or dependence on caregivers.

Taurursodiol adds a separate formulation issue. The active is a bile acid derivative with limited aqueous solubility and potential precipitation or incomplete dispersion if the formulation is poorly designed. Excipients must therefore support uniform wetting and dose delivery without creating excessive viscosity or sedimentation.

A successful follow-on formulation would need to show:

• Content uniformity for both active ingredients.
• Acceptable reconstitution time.
• Limited sedimentation or readily reversible sedimentation.
• Stability under controlled and accelerated conditions.
• Compatibility with common enteral feeding tubes.
• Acceptable taste, odor, and mouthfeel.
• Consistent delivery when mixed with approved beverages or soft foods.

What excipient strategy would improve Relyvrio?

The most valuable strategy is not simply substituting one filler or sweetener. It is redesigning the administration platform around dysphagia, caregiver use, and enteral feeding.

Taste-masking strategy

The bitter and salty taste of sodium phenylbutyrate is a central development target. Potential approaches include:

• High-intensity sweeteners.
• Flavors with stronger citrus or fruit profiles.
• Ion-exchange resin complexes.
• Lipid or polymeric coating of active particles.
• Microencapsulation.
• Co-granulation with taste-masking polymers.
• Effervescent or rapidly dispersing systems that reduce residence time in the mouth.

A taste-masked granule could create a stronger product than a conventional powder, but it would add manufacturing complexity and could affect dissolution, assay recovery, and bioequivalence.

Low-volume liquid formulation

A ready-to-use liquid or concentrated suspension could reduce caregiver preparation. The main technical risks are:

• Chemical degradation during storage.
• Taurursodiol precipitation.
• Increased preservative requirements.
• Microbial control.
• Higher shipping weight.
• More difficult stability management after opening.

A concentrated liquid may work better as a pharmacy-compounded or short-use product than as a long-shelf-life commercial product unless the sponsor develops a robust preservative and container-closure system.

Enteral-tube formulation

A tube-compatible product is commercially relevant because ALS patients may transition to percutaneous endoscopic gastrostomy (PEG) feeding. A dedicated formulation could be:

• A low-viscosity suspension.
• A granule dispersion with controlled particle size.
• A dual-chamber sachet.
• A liquid concentrate diluted immediately before administration.

Development must address tube clogging, adsorption to tubing, dose recovery after flushing, compatibility with enteral nutrition, and administration volume. These characteristics can support formulation patents and product differentiation even when the active ingredients are established.

Unit-dose stick pack

A stick pack could replace the larger packet format and improve portability. It could also support:

• Better moisture protection.
• Lower packaging material use.
• More efficient automated filling.
• Separate flavor variants.
• Easier caregiver handling.

The main limitation is that a 4 g active load plus excipients may require a relatively large stick pack. A high-density granule or agglomerated powder could reduce fill volume.

Dual-phase or multiparticulate product

A multiparticulate system could separate the two active ingredients or place one active in coated granules. This would create opportunities for:

• Improved stability.
• Better taste masking.
• Controlled dissolution.
• Reduced interaction between the active ingredients.
• Separate release profiles.

The commercial benefit would need to justify higher development and manufacturing costs. For an ALS product with uncertain market demand, a low-complexity powder or granule remains more commercially defensible than a sophisticated controlled-release system.

What formulation patents could protect a Relyvrio follow-on product?

The active ingredients are not new chemical entities. Patent value therefore would likely concentrate on formulation and use claims.

Potential patent categories

Patent category	Potential claim subject
Composition	Specific sodium phenylbutyrate-to-taurursodiol ratios
Formulation	Powder, granule, suspension, or multiparticulate composition
Taste masking	Coated particles, resin complexes, polymer matrices
Stability	Moisture-controlled formulations and packaging
Administration	PEG-tube delivery and flushing procedures
Dosage regimen	Twice-daily or disease-stage-specific dosing
Combination use	Use in ALS or related neurodegenerative diseases
Manufacturing	Blending, granulation, coating, and filling processes
Packaging	Moisture-barrier unit-dose systems

A formulation patent is strongest when it combines a defined composition with measurable technical effects, such as improved stability, reduced sedimentation, better tube recovery, or validated taste masking.

Broad claims covering only “sodium phenylbutyrate and taurursodiol” would face greater validity risk because the combination and the individual active ingredients were publicly known. Narrower claims directed to a particular excipient ratio, particle architecture, or administration method may be more defensible but provide less blocking power.

What is the Orange Book and exclusivity status of Relyvrio?

Relyvrio was approved by FDA in September 2022 for ALS.[2] Its regulatory protection must be analyzed separately from its patent position.

Orphan-drug exclusivity

Relyvrio received orphan-drug designation for ALS. Orphan-drug exclusivity generally provides seven years of market exclusivity from approval for the same drug and indication under the Orphan Drug Act.[3] On that basis, the nominal exclusivity period would extend into 2029, subject to the statutory rules governing withdrawal, marketing, and subsequent applications.

Orphan exclusivity is not the same as patent protection. It does not prevent all follow-on development, and it does not automatically block products that differ in indication, active ingredient, or legally relevant clinical characteristics.

Orange Book listing

The Orange Book provides the controlling public record for listed patents and regulatory exclusivity associated with an approved drug.[4] Relyvrio’s practical protection should be assessed through:

• Listed formulation patents.
• Method-of-use patents.
• Patent expiration dates.
• Any pediatric exclusivity.
• The status of the approved NDA after withdrawal.
• Whether an ANDA can be submitted and when approval or marketing could occur.

Because Relyvrio was withdrawn for commercial reasons rather than because of a safety recall, the regulatory consequences differ from a withdrawal based on safety or efficacy concerns. The FDA’s final regulatory treatment of the NDA and any remaining exclusivity determines the timing of a generic or follow-on approval.

When did Relyvrio lose commercial momentum?

Amylyx announced in March 2024 that the PHOENIX trial did not meet its primary or secondary efficacy endpoints. The company announced that it would discontinue marketing Relyvrio and Albrioza in the United States and Canada.[5]

The PHOENIX result changed the commercial assessment in three ways:

1. It reduced the value of a premium branded formulation.
2. It weakened the case for expensive taste-masking or controlled-release development.
3. It shifted attention toward low-cost access, generic supply, and evidence-based repurposing.

The withdrawal also limits the value of manufacturing capacity dedicated to a branded ALS product. A follow-on sponsor would need a substantially lower cost base or a new clinical rationale.

What commercial opportunities remain for Relyvrio excipients?

1. Generic or authorized-generic supply

The most direct opportunity is a lower-cost equivalent containing the same two active ingredients. A conventional powder for suspension would likely be more commercially rational than a complex reformulation.

The opportunity depends on:

• Remaining orphan exclusivity.
• Orange Book patents.
• FDA approval requirements.
• Availability and quality of sodium phenylbutyrate and taurursodiol.
• Market demand after branded withdrawal.
• Reimbursement and payer coverage.

A generic manufacturer could use a different excipient system if it demonstrates pharmaceutical equivalence and acceptable product performance.

2. Improved dysphagia product

A taste-masked granule, low-volume suspension, or PEG-compatible formulation could target patients unable to tolerate the original powder. This could support a 505(b)(2) strategy if the product relies partly on the existing Relyvrio data but introduces a meaningful formulation difference.

The commercial case is stronger if the product shows measurable benefits in:

• Administration time.
• Dose recovery through feeding tubes.
• Patient preference.
• Reduced caregiver burden.
• Reduced nausea or taste-related discontinuation.

3. Ex-US licensing

Amylyx commercialized the product in Canada under the name Albrioza. Ex-US licensing could remain relevant where local regulators, physicians, or patient groups maintain demand despite the negative PHOENIX result.

A license would likely require a low fixed-cost model. The most attractive structure would be regional manufacturing or supply licensing, not a large royalty commitment based on pre-withdrawal revenue expectations.

4. Combination products for other diseases

The two active ingredients have been investigated in other neurodegenerative conditions, including Wolfram syndrome and progressive supranuclear palsy. A new indication would require clinical evidence and would not automatically inherit the ALS commercial profile.

Excipient innovation could support a broader platform if the same formulation improves delivery across several neurologic diseases. The development strategy would need to avoid relying on the failed ALS efficacy outcome as the principal commercial justification.

5. Ingredient and contract-manufacturing services

Contract manufacturers may have an opportunity to supply:

• Sodium phenylbutyrate and taurursodiol blending.
• Moisture-controlled powder filling.
• Stick-pack production.
• Granulation and taste masking.
• Tube-compatibility testing.
• Stability and packaging services.

This opportunity is more predictable than launching a new Relyvrio-branded product because it generates revenue from manufacturing capability rather than clinical adoption.

How does Relyvrio compare with competing drug products?

Relyvrio occupied a specialized position in ALS treatment. It was not a direct formulation competitor to riluzole or edaravone, but it competed for treatment budgets, patient adherence, and physician attention.

Product	Active ingredient or platform	Dosage form	Commercial relevance
Relyvrio	Sodium phenylbutyrate plus taurursodiol	Oral powder	Withdrawn after negative PHOENIX results
Riluzole	Riluzole	Tablet, oral suspension, orally disintegrating tablet	Established generic competition
Radicava	Edaravone	IV infusion and oral suspension	Higher administration complexity and branded formulation differentiation
Sodium phenylbutyrate products	Sodium phenylbutyrate	Oral formulations	Existing taste and sodium-load challenges
Taurursodiol products	Taurursodiol	Various investigational or supplement contexts	Combination value depended on clinical evidence

Relyvrio’s formulation advantage was convenience relative to infusion therapy. Its weakness was the active-load burden, taste, and uncertain clinical value after PHOENIX.

What manufacturing and IP barriers affect a follow-on product?

The principal barrier is not synthesis of either active ingredient. It is production of a reproducible, acceptable oral product with stable performance.

Key barriers include:

• Sodium phenylbutyrate’s strong taste and odor.
• High total dose per administration.
• Moisture sensitivity.
• Uniform blending of two active ingredients with different physical properties.
• Powder flow and segregation during filling.
• Taurursodiol dispersibility.
• Dose recovery through feeding tubes.
• Packaging cost for moisture protection.
• Clinical and regulatory support for any new formulation.

A sponsor developing a conventional equivalent can reduce risk by preserving the powder format and using familiar excipients. A sponsor pursuing premium differentiation would need stronger evidence that the excipient system improves clinically relevant administration outcomes.

What is the generic launch risk for Relyvrio?

Generic launch risk is high from a market perspective and moderate from a technical perspective.

Technical development is manageable because both actives are chemically defined and the original product is an oral powder. Commercial demand is less certain because:

• The branded product was withdrawn.
• PHOENIX failed to demonstrate benefit.
• Physician adoption may remain low.
• Payers may resist coverage.
• Orphan exclusivity and Orange Book patents may delay approval.
• A small ALS market may not support multiple manufacturers.

The most viable launch scenario is a low-cost, carefully targeted product for patients and clinicians who continue to seek access, combined with a formulation that materially improves administration.

Key Takeaways

• Relyvrio combined 3 g sodium phenylbutyrate with 1 g taurursodiol per packet.
• Its excipient value centered on taste management, powder flow, dispersibility, and moisture stability.
• The strongest formulation opportunities are taste-masked granules, PEG-tube-compatible suspensions, and lower-volume administration systems.
• Relyvrio’s commercial withdrawal followed the negative PHOENIX Phase 3 trial, sharply reducing the value of premium reformulation.
• A generic or authorized-generic powder is more commercially plausible than a complex controlled-release product.
• Patent opportunities are concentrated in formulation, taste masking, tube delivery, manufacturing, packaging, and method-of-use claims.
• Orphan-drug exclusivity and Orange Book status remain separate from the product’s commercial withdrawal and must be assessed independently.
• Contract manufacturing, excipient technology, and ex-US licensing may offer better risk-adjusted opportunities than a new branded ALS launch.

FAQs

Can excipients make a generic Relyvrio product patentable?

Yes. A specific excipient composition, coated particle structure, stability profile, or tube-delivery method can support patent protection if it is novel, nonobvious, and adequately supported by data. Excipients alone do not create blocking rights without a patentable technical combination.

Which excipient approach best addresses sodium phenylbutyrate taste?

A coated multiparticulate or microencapsulated granule is likely to provide stronger taste masking than a conventional sweetened powder. The tradeoff is higher manufacturing cost and greater risk of altered dissolution or incomplete dose recovery.

Is a liquid Relyvrio formulation commercially attractive?

A liquid could reduce preparation steps, but it introduces stability, preservation, shipping, and precipitation risks. A short-use concentrated suspension may be more practical than a long-shelf-life ready-to-drink product.

Could a Relyvrio follow-on product use a 505(b)(2) application?

A reformulated product could potentially use the 505(b)(2) pathway if it relies in part on FDA findings for the approved product while adding new formulation or administration data. The pathway would not eliminate the need to address applicable exclusivity and patent barriers.

Are biosimilars relevant to Relyvrio?

No. Relyvrio contains small-molecule active ingredients, not a biologic. Follow-on products would generally be evaluated through generic or 505(b)(2) pathways rather than the biosimilar pathway.

References

1. U.S. Food and Drug Administration. (2022). Relyvrio prescribing information.
2. U.S. Food and Drug Administration. (2022, September 29). FDA grants accelerated approval to new drug for patients with amyotrophic lateral sclerosis.
3. U.S. Congress. (1983). Orphan Drug Act, 21 U.S.C. § 360bb et seq.
4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
5. Amylyx Pharmaceuticals, Inc. (2024, March 8). Amylyx Pharmaceuticals announces topline results from PHOENIX trial of AMX0035 in ALS and plans for Relyvrio/Albrioza withdrawal.
6. Paganoni, S., Macklin, E. A., Hendrix, S., et al. (2024). Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis. New England Journal of Medicine, 390, 1161-1172.