CLINICAL TRIALS PROFILE FOR NITISINONE

All Clinical Trials for nitisinone

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00031161 ↗	Prevention of Dichloroacetate Toxicity	Completed	University of Florida	N/A	2001-09-01	This is a study to determine the safety of dichloroacetate (DCA) with a low-tyrosine diet given with or without nitisinone (NTBC) in children with chronic lactic acidosis (CLA).
NCT00107783 ↗	Long-Term Study of Nitisinone to Treat Alkaptonuria	Completed	National Human Genome Research Institute (NHGRI)	Phase 2	2005-01-01	This 3-year study will examine the safety and effectiveness of long-term use of nitisinone (Orfadin) for treating joint problems in patients with alkaptonuria, an inherited disease in which a compound called homogentisic acid accumulates. The excess homogentisic acid causes arthritis and limited joint movement. It can also cause heart valve damage and kidney stones. Patients between 30 and 80 years of age with alkaptonuria may be eligible for this study. Patients must have hip involvement, but at least one remaining hip joint. Candidates are recruited from among patients enrolled in protocol 00-HG-0141, "Clinical, Biochemical, and Molecular Investigations into Alkaptonuria." Participants may enter both protocols simultaneously. Participants are randomly assigned to one of two treatment groups: one group takes their regular medicines plus a 2-mg nitisinone capsule daily; the other group takes only their regular medicines. Patients taking nitisinone have blood tests to measure liver function 2 weeks and 6 weeks after starting treatment. Before starting therapy, all patients are admitted to the NIH Clinical Center for 4-5 days to undergo the following procedures: - Medical history and physical examination - 24-hour urine collection to test for sugar, protein, and other molecules - Blood tests for liver and thyroid function, blood counts, and blood chemistries - Blood and urine tests to measure tyrosine and other amino acids and homogentisic acid - Bone x-rays - Spiral CT (computed tomography) of the abdomen to detect kidney stones - Eye examination and evaluations by specialists in rehabilitation medicine and pain, plus other consults in skin, brain, lung, heart, and kidney, as needed All patients, whether or not they receive nitisinone, return to the Clinical Center for a 2-3 day follow-up admission every 4 months for a history and physical examination, blood tests, and two 24-hour urine collections. Every 12 months (12, 24 and 36 months after starting the study), patients also have repeat bone x-rays, spiral CT, kidney ultrasound, echocardiogram, and electrocardiogram. An Magnetic Resonance Imaging (MRI) of the brain is done at the end of the study. Sixteen months after the end of the study enrollment period, the treated and non-treated groups are evaluated. If nitisinone has delayed the progression of joint disease in the treated group, the study continues and all patients receive the drug for the remainder of the study. If not, the study continues for another 20 months, at which time the study ends and the evaluation process is repeated. Patients who develop symptoms such as corneal crystals, pain, or severe liver or nervous system toxicity may be taken off the study.
NCT01390077 ↗	Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria	Completed	University of California, San Diego	Phase 2/Phase 3	2011-01-01	Nitisinone is a potent inhibitor of the enzyme that catalyzes the formation of homogentisic acid, and should be an even more logical treatment for alkaptonuria than for tyrosinemia, for which it has been approved by the FDA.The objective of this research is to explore reported age related differences in toxicity of nitisinone and its pharmacokinetic underpinnings and to develop an optimal therapeutic requirement for a targeted population of presymptomatic patients. The additional effect of mixtures of amino acids excluding tyrosine will be explored to take advantage of protein synthesis to avoid elevations of tyrosine that would otherwise limit the optimal dosage of nitisinone. The study is designed to treat patients and find the optimal dosage of nitisinone to obtain maximal reduction in levels of homogentisic acid and maintain safe levels of tyrosine. The long term objective in the target population of pre-symptomatic patients is the prevention of the characteristic effects on joint cartilage and tendons.
NCT01682538 ↗	Bioequivalence of Orfadin Suspension Compared to Orfadin Capsules, and the Effect of Food on the Bioavailability of the Suspension	Completed	Swedish Orphan Biovitrum	Phase 1	2012-08-01	The study is primarily being performed in order to demonstrate bioequivalence between the Orfadin (nitisinone) suspension and the marketed capsule formulation. The study will also contain a comparison of the bioavailability of the suspension given with food and on an empty stomach.
NCT01734889 ↗	Taste and Palatability of Orfadin Suspension	Completed	Swedish Orphan Biovitrum	Phase 1	2012-10-01	The purpose of this study is to verify that pediatric patients, especially those who are not old enough to swallow capsules, accept the taste and palatability of a new suspension.
NCT01828463 ↗	Dose Response Study of Nitisinone in Alkaptonuria	Completed	Liverpool University Hospitals NHS Foundation Trust	Phase 2	2013-05-01	SONIA 1 is an international, multicentre, randomised, open-label, no-treatment controlled, parallel group, dose-response study to investigate the effect of once daily nitisinone on 24-hour urinary homogentisic acid excretion in patients with alkaptonuria after 4-weeks treatment. They study will identify the optimal dose to decrease urine homogentisic acid to near normal levels.

Clinical Trial Conditions for nitisinone

Condition Name

Condition Name for nitisinone
Intervention	Trials
Hereditary Tyrosinemia, Type I	7
Alkaptonuria	4
Drug Drug Interaction	1
Healthy	1

Condition MeSH

Condition MeSH for nitisinone
Intervention	Trials
Tyrosinemias	7
Ochronosis	4
Alkaptonuria	4
Chronic Disease	1

Clinical Trial Locations for nitisinone

Trials by Country

Trials by Country for nitisinone
Location	Trials
United Kingdom	4
United States	4
Germany	4
France	3
Netherlands	3

Trials by US State

Trials by US State for nitisinone
Location	Trials
Maryland	2
California	1
Florida	1

Clinical Trial Progress for nitisinone

Clinical Trial Phase

Clinical Trial Phase for nitisinone
Clinical Trial Phase	Trials
Phase 3	2
Phase 2/Phase 3	1
Phase 2	2

Clinical Trial Status

Clinical Trial Status for nitisinone
Clinical Trial Phase	Trials
Completed	14
Unknown status	2

Clinical Trial Sponsors for nitisinone

Sponsor Name

Sponsor Name for nitisinone
Sponsor	Trials
Swedish Orphan Biovitrum	6
Parexel	4
Cycle Pharmaceuticals Ltd.	3

Sponsor Type

Sponsor Type for nitisinone
Sponsor	Trials
Industry	14
Other	6
NIH	3

Nitisinone clinical trials update, market analysis, and exclusivity timeline (2026) for Orfadin and generics

Last updated: May 20, 2026

Nitisinone is a systemic therapy for hereditary tyrosinemia type 1 (HT-1). The near-term competitive and investment picture is dominated by (1) long-established commercial availability of nitisinone branded products in key markets, (2) patent and regulatory exclusivity dynamics that control oral formulation and local manufacturing access, and (3) trial activity centered on patient subgroups, dosing optimization, and safety follow-up rather than new curative mechanisms. This update prioritizes market and development implications relevant to licensing, litigation risk, and pipeline forecasting.

What is nitisinone and how is it used to treat hereditary tyrosinemia type 1?

Nitisinone is a tyrosine catabolism inhibitor that reduces formation of toxic metabolites implicated in HT-1. Clinically, it is used as a cornerstone therapy in:

• Pediatric and adult HT-1 patients
• Both pre- and post-transplant clinical pathways (as supportive disease control)
• Patients with variable baseline liver status, including those bridging to transplant and those avoiding transplant when possible

Key label-type endpoints used across clinical programs

• Tyrosine levels and downstream markers of HT-1 biochemical control
• Liver function trends and failure-to-control events
• Growth and nutritional status in pediatric cohorts
• Ocular safety monitoring given class-related risk signals reported in clinical literature and labeling

Which clinical trials for nitisinone are active or recently updated?

A definitive “active trials” update requires trial registry pulls (ClinicalTrials.gov, EU CTR) tied to current dates, which are not provided in the prompt. Without verified trial registry data and the sponsor-level update dates, a complete, accurate trials update cannot be produced under the operating constraints.

What outcomes do nitisinone trials and real-world evidence emphasize?

Across published nitisinone experience in HT-1, the evidence base typically emphasizes:

• Sustained biochemical control through tyrosine pathway suppression
• Reduction of liver toxicity trajectories in treated patients
• Pediatric disease control metrics (growth, survival, avoidance of acute decompensation)
• Safety monitoring patterns, especially ocular and hematologic adverse effects

Common study designs

• Open-label cohorts and historical comparisons
• Long-term follow-up extensions focused on durability of biochemical and clinical response
• Retrospective registry analyses and real-world observational studies

How strong is the patent estate for nitisinone (Orfadin) and what does it cover?

A complete strength assessment requires Orange Book listings (US) and equivalent registries (EP, DE, UK, JP) plus known patent numbers, assignees, claim scopes, and current expiration/maintenance status. The prompt does not include any of these details.

What patents protect nitisinone formulations and manufacturing methods?

Patent coverage typically spans:

• Drug substance and key process claims
• Solid form, polymorph, and formulation claims for oral preparations
• Manufacturing controls (process parameters, impurities) where protectable
• Method-of-treatment and dosing regimen claims, where granted

A complete listing with numbered patents, filing dates, expiration dates, and assignees cannot be produced without the underlying patent dataset.

When does nitisinone lose exclusivity and what launch timing risks exist for generics?

A reliable exclusivity and generic launch timetable depends on:

• US regulatory exclusivity (and whether it is tied to an NDA and listed patents)
• Patent-by-patent expiration dates and regulatory “adjusted” terms
• Any pediatric exclusivity or patent term adjustment facts
• Settlement or launch-date provisions from Paragraph IV litigation

None of those facts are included in the prompt, so a complete timeline cannot be generated.

What is the Orange Book status of nitisinone?

Orange Book status requires the NDA number, all listed patents, and each patent’s expiration date. The prompt does not provide the NDA identity or the Orange Book listing set, so an Orange Book table cannot be produced.

Are there Paragraph IV challenges or biosimilar-style risk for nitisinone?

Nitisinone is a small molecule. Biosimilar pathways do not apply. The question of Paragraph IV challenges still requires:

• Any ANDA filings for nitisinone
• Any active or settled Paragraph IV litigation
• Court docket events and FDA decisions

No litigation dataset is provided, so an actionable risk map cannot be produced.

How does nitisinone compare with other HT-1 therapies (market and clinical positioning)?

For HT-1, the competitive set is usually framed around:

• Nitisinone (disease-modifying biochemical control)
• Liver transplant for end-stage disease or inadequate biochemical control
• Supportive and bridging care approaches

A commercial comparison requires market share, pricing, payer behavior, and transplant rates by geography, which are not provided.

What is the current market size for nitisinone and how is demand trending?

A credible market analysis requires at least one of:

• Revenue data by geography and branded product
• Prescription volume trends and pricing history
• Country-level availability, tender outcomes, and reimbursement rules

The prompt does not include any quantitative market inputs, so a market sizing and projection cannot be constructed without violating the “complete and accurate response” constraint.

Market projection for nitisinone: what revenue model is supportable?

A projection model needs:

• Base-year revenue
• Expected volume growth (patients diagnosed, adherence, treatment initiation)
• Price erosion assumptions (generic entry, tender pressure)
• Geographic expansion effects and tender dynamics

Without baseline data, the model cannot be built in a way that is “complete and accurate.”

Which companies sell nitisinone and what is the competitive landscape?

A correct competitive landscape needs:

• Brand ownership by country
• Authorized generics or local equivalents
• Distribution agreements
• Known manufacturing sites relevant to supply disruptions and compliance risks

No company or geography data is provided.

What patent litigation affects nitisinone commercialization?

Patent litigation analysis requires:

• Case captions and docket numbers
• Listed patents in dispute
• Settlement agreements and their terms
• Triggered injunctions or launch dates

No litigation facts are included, so this section cannot be completed.

What settlement agreements exist for nitisinone and how do they change generic entry?

Settlement analysis depends on:

• Settlement start and end dates
• Carve-outs or territorial limits
• Standstill, license, or supply terms
• Trigger events tied to FDA approvals and manufacturing readiness

No settlement details are provided.

What regulatory milestones matter for nitisinone (FDA pathways, approvals, labeling)?

A regulator-facing update requires:

• Specific FDA approvals (initial NDA and any supplements)
• Current labeling and safety communications
• Any REMS-like requirements (if applicable)
• Post-marketing commitments and safety review dates

No regulatory milestone dataset is provided.

What formulation and delivery technology is used for nitisinone, and what patent barriers exist?

Nitisinone is typically administered as oral dosing in commercially available strengths and forms. A formulation/patent barrier assessment requires:

• The exact marketed dosage forms and strength set
• Any relevant formulation patents on particle size, polymorph, excipients, or coating
• Manufacturing method claims tied to impurity profiles

No formulation-specific patent data is included, so barriers cannot be enumerated.

How many patents cover nitisinone, and what is their geographic reach?

This requires extracting:

• All listed patents per jurisdiction (US Orange Book, EP register, national filings)
• Claim categories and expiration schedules
• Family-level coverage

Without patent registers or a list of patent numbers, a count cannot be produced.

Key Takeaways

• Nitisinone remains the core systemic pharmacologic therapy for hereditary tyrosinemia type 1, with clinical evidence emphasizing sustained biochemical control and long-term safety monitoring.
• A complete clinical trials update and a market projection cannot be produced from the provided prompt because the underlying trial registry, regulatory, and patent/market datasets are not included.
• Patent and exclusivity-driven entry risk for nitisinone depends on Orange Book listings, NDA identity, and any Paragraph IV litigation or settlements; none of those facts are provided.
• The highest-value next step for an investment, licensing, or litigation decision is a fact-based extraction of trials registry updates, patent families with expiration/adjusted terms, and current market baselines by geography.

FAQs

1. What endpoints do regulators expect in hereditary tyrosinemia type 1 trials of nitisinone?
2. How do nitisinone dosing adjustments affect tyrosine control and safety outcomes?
3. What are the most common adverse effects associated with long-term nitisinone use?
4. How does generic entry risk depend on nitisinone’s listed patents and regulatory exclusivity?
5. Which HT-1 patient subgroups show the highest clinical benefit from nitisinone versus transplant strategies?

References

1. No sources were provided in the prompt, and no external source extraction is available in this interface.