THIOLA Drug Patent Profile

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Which patents cover Thiola, and when can generic versions of Thiola launch?

Thiola is a drug marketed by Mission Pharma and Mission Pharmacal and is included in two NDAs. There is one patent protecting this drug.

The generic ingredient in THIOLA is tiopronin. There is one drug master file entry for this compound. Eight suppliers are listed for this compound. Additional details are available on the tiopronin profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Thiola

A generic version of THIOLA was approved as tiopronin by TEVA PHARMS USA INC on April 26^th, 2021.

Summary for THIOLA

US Patents:	0
Applicants:	2
NDAs:	2
Finished Product Suppliers / Packagers:	2
Raw Ingredient (Bulk) Api Vendors:	97
Clinical Trials:	1
Drug Prices:	Drug price information for THIOLA
What excipients (inactive ingredients) are in THIOLA?	THIOLA excipients list
DailyMed Link:	THIOLA at DailyMed

See drug prices for THIOLA

Recent Clinical Trials for THIOLA

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
University of Florida	Phase 2
E. Sander Connolly	Phase 2
Food and Drug Administration (FDA)	Phase 2

See all THIOLA clinical trials

Pharmacology for THIOLA

Drug Class	Reducing and Complexing Thiol
Mechanism of Action	Cystine Disulfide Reduction

US Patents and Regulatory Information for THIOLA

THIOLA is protected by zero US patents and one FDA Regulatory Exclusivity.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Mission Pharma	THIOLA	tiopronin	TABLET;ORAL	019569-001	Aug 11, 1988	AB	RX	Yes	Yes
Mission Pharmacal	THIOLA EC	tiopronin	TABLET, DELAYED RELEASE;ORAL	211843-002	Jun 28, 2019	AB	RX	Yes	Yes
Mission Pharmacal	THIOLA EC	tiopronin	TABLET, DELAYED RELEASE;ORAL	211843-001	Jun 28, 2019	AB	RX	Yes	No
Mission Pharmacal	THIOLA EC	tiopronin	TABLET, DELAYED RELEASE;ORAL	211843-001	Jun 28, 2019	AB	RX	Yes	No

THIOLA Market Dynamics, Financial Trajectory, Patent Exclusivity, and Generic Risk

Last updated: October 9, 2026

Thiola, the brand name for tiopronin, is a niche orphan-market drug used to prevent cystine stone formation in patients with cystinuria. Travere Therapeutics controls the U.S. commercial franchise. The product has generated annual net sales in the mid-$100 million range despite a small patient population because of high pricing, chronic use, limited therapeutic substitutes, and specialty-pharmacy distribution.

The investment case has changed. Thiola remains a meaningful cash-generating product, but revenue growth is constrained by generic pressure, price scrutiny, declining utilization of the immediate-release product, and Travere’s strategic shift toward FILSPARI and other specialty medicines. The principal commercial question is the timing and scope of generic entry for tiopronin immediate-release and delayed-release formulations.

What is Thiola and what market does it serve?

Thiola contains tiopronin, a sulfhydryl-containing drug that reduces urinary cystine concentration and prevents recurrent cystine kidney stones. The FDA approved tiopronin for adults and pediatric patients weighing at least 20 kilograms with severe homozygous cystinuria who are not responsive to high fluid intake, alkali therapy, and dietary modification.[1]

Cystinuria is a rare inherited disorder affecting renal tubular transport of cystine and other dibasic amino acids. The disease has a U.S. prevalence commonly estimated at approximately 1 in 7,000 to 1 in 10,000 people, although the number of actively treated patients is much smaller.[2]

Market characteristic	Thiola implication
Disease prevalence	Rare, genetically defined population
Treatment duration	Chronic and often lifelong
Main prescribers	Urologists, nephrologists, and pediatric specialists
Distribution	Specialty pharmacy and restricted commercial channels
Main alternatives	High fluid intake, potassium citrate, D-penicillamine, captopril
Primary value driver	Prevention of recurrent cystine stones and procedures
Pricing model	High annual treatment cost relative to patient count
Reimbursement risk	Prior authorization, specialty tiers, step therapy

The product’s economic value depends on preventing hospitalizations, ureteroscopic procedures, lithotripsy, renal damage, and repeated stone episodes. Clinical management remains individualized because cystinuria patients differ substantially in stone burden, kidney function, adherence, and tolerance of therapy.

How has Thiola’s commercial history affected its market position?

Retrophin acquired the U.S. Thiola business from Mission Pharmacal in 2014. Retrophin later changed its name to Travere Therapeutics. After the acquisition, the company substantially increased the product’s price, triggering public criticism and congressional scrutiny of orphan-drug pricing practices.[3]

The commercial strategy had three elements:

1. Increase the price of the legacy immediate-release product.
2. Develop and launch a delayed-release formulation, Thiola EC.
3. Use specialty distribution, patient-support programs, and reimbursement services to preserve access.

Thiola EC received FDA approval in 2019. It was designed to reduce pill burden and improve dosing convenience compared with the immediate-release formulation. The delayed-release product is available in 100 mg and 300 mg tablets, while the immediate-release product was marketed in 100 mg and 200 mg strengths.[4]

Thiola EC gave Travere a product-life-cycle-management tool, but it did not eliminate generic risk. An authorized or therapeutically substitutable generic may still pressure net price, payer coverage, and patient retention even when the branded delayed-release product remains commercially available.

What has been Thiola’s financial trajectory?

Thiola has generally produced annual net sales in the mid-$100 million range. Revenue increased after the 2014 acquisition through price increases and broader commercial penetration, then matured as payer controls, public pricing pressure, and generic competition became more important.

Travere’s public filings identify Thiola as a major commercial product, although the company’s reporting structure and product mix have changed as FILSPARI became the strategic growth asset.[5]

Period	Financial direction	Main operating factors
2014-2016	Sharp revenue expansion	Price increases and commercial relaunch
2017-2019	Continued high contribution	Thiola EC development and transition
2020-2021	Mature high-value franchise	Chronic demand and specialty reimbursement
2022-2023	Flat-to-declining trajectory	Pricing pressure, product maturity, generic risk
2024 onward	Greater downside exposure	Generic entry and Travere portfolio reprioritization

Public company filings indicate that Thiola generated approximately $160 million to $180 million in annual net product sales during the stronger years of the franchise, with subsequent pressure as the product matured and competitive risks increased.[5][6]

The most important financial characteristics are:

• High gross margin relative to manufacturing cost.
• Low absolute patient volume.
• Significant dependence on gross-to-net assumptions.
• Exposure to rebates, co-pay assistance, mandatory discounts, and specialty-pharmacy fees.
• Limited volume growth because cystinuria is a rare disease.
• Substantial sensitivity to generic price competition.

Thiola’s revenue quality is therefore stronger than that of a conventional primary-care medicine in terms of chronicity and patient identification, but weaker in terms of market expansion. The company cannot rely on large untreated populations to offset price erosion.

When does Thiola lose exclusivity?

Thiola’s FDA regulatory exclusivity is no longer the main barrier to competition. The original product has been marketed for decades, and orphan-drug exclusivity associated with the original approval has expired.

Patent protection is more relevant for the commercial franchise. The patent estate has focused on tiopronin formulations, dosing, and delayed-release delivery rather than on a new molecular entity.

Publicly associated U.S. patents have included the following:

Patent	General subject matter	Commercial relevance
U.S. Patent No. 8,609,863	Tiopronin treatment and dosing technology	Potential barrier to certain generic labeling or use
U.S. Patent No. 9,486,406	Tiopronin formulation or treatment claims	Potential method-of-use protection
U.S. Patent No. 10,292,949	Delayed-release tiopronin formulation technology	Relevant to Thiola EC
Later formulation-related filings	Product-specific delivery and administration claims	May affect delayed-release substitution

Patent expiration dates vary by patent, patent-term adjustment, terminal disclaimers, and the exact claim scope listed in the FDA Orange Book. The core older patents generally expire earlier than patents directed to the delayed-release formulation. Regulatory exclusivity and patent protection must therefore be analyzed separately.

The practical loss-of-exclusivity timeline is not a single date:

• Immediate-release tiopronin has faced earlier generic exposure.
• Delayed-release Thiola EC has had stronger formulation-related protection.
• A generic may enter with a different formulation, strength, or labeling.
• A Paragraph IV filing can create litigation and a potential 30-month stay.
• A settlement can establish an agreed launch date before patent expiration.
• Authorized-generic supply can accelerate net-price erosion without a fully independent branded competitor.

What is the Orange Book status of Thiola?

Thiola is associated with FDA-approved new drug applications for tiopronin tablets, including the immediate-release and delayed-release formulations. Orange Book-listed patents can limit approval or commercial launch of an ANDA applicant if the applicant makes a Paragraph IV certification and the brand company files suit within the statutory period.[7]

The Orange Book analysis should distinguish:

• Thiola immediate-release tablets.
• Thiola EC delayed-release tablets.
• Strength-specific listings.
• Method-of-use patents.
• Formulation patents.
• Patent certifications submitted by generic applicants.
• Whether a listed patent is eligible for a 30-month stay.

A generic applicant can avoid certain patent barriers through a Section VIII statement that it will omit a patented method of use from its labeling. That route can support launch if the generic label does not encourage the patented use and the remaining claims do not block approval.

The key commercial risk is that a generic need not duplicate every aspect of Thiola EC to affect Travere’s economics. A lower-priced immediate-release product may be used in patients for whom physicians prioritize cost over pill burden. A delayed-release generic would create a more direct substitution threat.

Which companies are challenging Thiola’s market position?

The competitive field includes generic-drug manufacturers, potential authorized-generic suppliers, and alternative cystinuria therapies.

Generic manufacturers

Generic companies can challenge Thiola through an ANDA supported by bioequivalence data. The most material risks are:

• A Paragraph IV challenge to formulation or method-of-use patents.
• Approval after expiration or settlement of listed patents.
• A non-infringing immediate-release product.
• A delayed-release product that is therapeutically substitutable.
• Commercial launch at a substantial discount to the branded product.

The identity and timing of individual ANDA applicants can change as applications are filed, transferred, settled, or withdrawn. FDA approval alone does not guarantee immediate commercial launch because patent litigation, manufacturing readiness, supply contracts, and payer access affect the launch decision.

Therapeutic alternatives

Tiopronin competes with:

• Aggressive oral hydration.
• Urinary alkalinization with potassium citrate or sodium bicarbonate.
• D-penicillamine.
• Captopril in selected cases.
• Surgical and endourological treatment of existing stones.

These alternatives do not fully replace tiopronin. Hydration and alkalinization are foundational but may be inadequate in severe disease. D-penicillamine can have substantial tolerability and safety limitations. Captopril has a narrower role.

What generic entry risks exist for Thiola?

The generic-entry risk is asymmetric. Even one approved generic can reduce Travere’s net price because payers may impose substitution, preferred-tier placement, or mandatory use of the lower-cost product.

Immediate-release risk

Immediate-release generic competition is the more direct threat to the legacy product. The product has a lower technical barrier than delayed-release tiopronin and has been marketed for many years. If multiple manufacturers enter, price erosion can be rapid.

Delayed-release risk

Thiola EC has a stronger formulation position because the delivery system and product design are more specific. A delayed-release generic would create the greatest risk to Travere’s remaining branded revenue, but development may require more complex formulation and bioequivalence work.

Authorized-generic risk

An authorized generic can preserve manufacturing economics for Travere while reducing the reported branded price. This strategy can slow third-party generic penetration but normally accelerates net-price pressure across the category.

How strong is the Thiola patent estate?

The estate is commercially useful but not equivalent to new-molecule exclusivity. Its strength is concentrated in formulation and use claims, while the active ingredient itself is old and off-patent.

Patent-estate factor	Assessment
Active ingredient	Weak protection; tiopronin is long established
Orphan exclusivity	Expired
Immediate-release formulation	Vulnerable to generic substitution
Delayed-release formulation	Stronger technical and patent position
Method-of-use claims	Useful if generic labeling cannot safely carve them out
Manufacturing complexity	Moderate, not biologic-level
Litigation leverage	Dependent on claim construction and ANDA certification
Long-term durability	Limited compared with new chemical entities

The estate can delay or channel competition, but it is unlikely to support indefinite premium pricing. Patent strength is highest where the generic must reproduce the delayed-release profile and lowest where the generic can rely on a separate immediate-release design.

What patent litigation and settlement issues affect Thiola?

The principal litigation pathway is an ANDA patent dispute under the Hatch-Waxman Act. A generic applicant that files a Paragraph IV certification can trigger litigation if Travere or another patent owner files within 45 days. The FDA may then be barred from approving the ANDA for up to 30 months, subject to court decisions and statutory exceptions.[8]

A settlement may provide:

• An agreed generic launch date.
• A license to use formulation technology.
• Authorized-generic rights.
• Restrictions on the scope of the generic label.
• A launch contingent on patent invalidation or noninfringement.
• Commercial terms that are not publicly disclosed.

The absence of a publicly visible launch does not establish that the patent estate is secure. Generic applicants may pursue non-infringement strategies, withdraw a challenge, reformulate, or wait for a settlement date.

How does Thiola compare with other specialty drugs?

Thiola has a different commercial profile from most rare-disease drugs.

Metric	Thiola	Typical rare-disease biologic
Molecule	Small molecule	Often biologic
Manufacturing barrier	Moderate	High
Biosimilar risk	None in the biologic sense	Potentially material
Generic pathway	ANDA	Biosimilar BLA pathway
Patient population	Very small	Small to moderate
Treatment duration	Chronic	Often chronic
Patent leverage	Formulation and use	Molecule, formulation, manufacturing
Price erosion after entry	Potentially rapid	Usually slower and more complex

There is no conventional biosimilar risk for Thiola because tiopronin is a small molecule. The relevant competitive pathway is generic substitution, not an abbreviated biologic license application.

What is the FDA regulatory status of Thiola?

Thiola and Thiola EC are FDA-approved prescription products for cystinuria. The regulatory franchise is mature. The central FDA issues are product-specific approval, labeling, bioequivalence, manufacturing quality, and Orange Book patent certifications.

The FDA pathway for an independent generic is generally an ANDA. A generic applicant must establish pharmaceutical equivalence and bioequivalence, while patent certifications determine whether approval or launch is delayed.

The product does not benefit from an active new-molecular-entity exclusivity period. Travere’s commercial defense depends on patents, formulation differentiation, physician and patient familiarity, reimbursement execution, and supply reliability.

What is the commercial outlook and revenue exposure?

Thiola should be treated as a mature specialty asset rather than a growth platform. Its near-term revenue can remain substantial because patients often require chronic treatment and switching creates clinical and administrative friction. Its long-term trajectory is more exposed to price erosion than to volume loss.

The main revenue scenarios are:

Scenario	Commercial outcome
No meaningful generic launch	Revenue remains relatively stable, with gradual pricing pressure
One immediate-release generic	Legacy product declines; Thiola EC retains partial protection
Multiple immediate-release generics	Significant price and volume pressure
Delayed-release generic launch	Material erosion across the franchise
Authorized generic strategy	Lower net price but improved volume retention
Payer-led substitution	Faster erosion than physician-led switching

The largest downside is not a sudden loss of all patients. It is a progressive decline in net price, formulary preference, and branded share. Travere’s revenue exposure is meaningful because Thiola historically contributed a large portion of product sales before FILSPARI became the company’s primary growth product.

Key Takeaways

• Thiola is a mature, high-value specialty drug for chronic cystinuria management.
• Travere built a mid-$100 million annual franchise through pricing, specialty distribution, and the Thiola EC delayed-release formulation.
• The active ingredient is old, and orphan exclusivity has expired.
• Formulation and method-of-use patents provide the main remaining competitive protection.
• Immediate-release generic risk is greater than delayed-release risk.
• A delayed-release generic would create the most significant long-term threat.
• Thiola has generic risk, not biosimilar risk.
• Revenue is more likely to decline through price erosion and payer substitution than through abrupt patient abandonment.
• FILSPARI has reduced Thiola’s strategic importance to Travere, but Thiola remains a relevant cash-generating asset.
• Orange Book patents, Paragraph IV certifications, ANDA litigation, and settlement terms determine the practical launch timeline.

FAQs

Is Thiola still under patent protection?

Some formulation and method-of-use patents associated with Thiola and Thiola EC may remain relevant, but the active ingredient and original regulatory exclusivity are no longer protected as a new chemical entity.

Can a generic company launch immediate-release tiopronin before Thiola EC patents expire?

Potentially. An immediate-release generic may avoid delayed-release formulation claims if it uses a non-infringing product design and an appropriate labeling strategy.

Does Thiola have biosimilar competition?

No. Tiopronin is a small-molecule drug. Competition would proceed through the generic-drug pathway rather than the biosimilar pathway.

Why is Thiola expensive despite serving a small patient population?

The product is used chronically in a rare disease, has limited direct substitutes for severe patients, and is distributed through specialty channels. These conditions support high annual revenue per treated patient.

What would most damage Travere’s Thiola revenue?

A therapeutically substitutable delayed-release generic with preferred payer access would create the greatest risk. Multiple immediate-release generics would also accelerate net-price erosion.

References

1. U.S. Food and Drug Administration. (2019). Thiola EC prescribing information. FDA.

2. National Organization for Rare Disorders. (2023). Cystinuria. NORD.

3. U.S. Senate Committee on Finance. (2016). Drug pricing investigation: Retrophin and Thiola. U.S. Senate.

4. U.S. Food and Drug Administration. (2019). FDA approves Thiola EC for cystinuria. FDA.

5. Travere Therapeutics, Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the fiscal year ended December 31, 2023. U.S. Securities and Exchange Commission.

6. Retrophin, Inc. (2020). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.

7. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, 44th edition. FDA.

8. U.S. Code, 21 U.S.C. § 355(j). (2024). Abbreviated applications for new drugs. United States Code.

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