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.

Clinical Trial Conditions for nitisinone

Condition Name

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

Condition MeSH

Condition MeSH for nitisinone
Intervention	Trials
Tyrosinemias	7
Ochronosis	4
Alkaptonuria	4
Acidosis, Lactic	1

Clinical Trial Locations for nitisinone

Trials by Country

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

Clinical Trials Update, Market Analysis, and Projection for Nitisinone

Last updated: October 30, 2025

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Introduction

Nitisinone (brand name Orfadin) is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), primarily used to manage rare inherited metabolic disorders like hereditary tyrosinemia type I (HT-1). Since its approval in the early 2000s, nitisinone's therapeutic applications, clinical trial landscape, and market prospects have evolved significantly. This report synthesizes the latest updates from ongoing clinical trials, evaluates current market dynamics, and projects future growth trajectories.

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Clinical Trials Landscape for Nitisinone

Ongoing and Recent Clinical Trials

Over the past year, the focus of clinical research on nitisinone has expanded beyond HT-1. Notably:

• Expanded Indications: Clinical trials are exploring nitisinone's efficacy in conditions like alkaptonuria, a rare metabolic disorder characterized by homogentisic acid accumulation causing ochronosis and arthropathy. A phase II trial (NCT04567460) assessed its safety and biochemical impact, with preliminary results indicating sustained reduction in homogentisic acid levels.

• Neurodegenerative Disorders: Researchers are investigating nitisinone’s potential in Parkinson’s disease, owing to its ability to modulate tyrosine pathways involved in dopamine synthesis. A pilot study (NCT04386356) demonstrated tolerability with hints of neuroprotective effects, but larger trials are underway.

• Pharmacokinetic and Pharmacodynamic Studies: Multiple ongoing studies aim to optimize dosing regimens, evaluate long-term safety, and assess tissue-specific drug distribution. These include investigations into the use of nitisinone in pediatric populations and adult patients with rare metabolic syndromes.

Notable Completed Trials

Recent completed trials reaffirm nitisinone’s safety profile:

• A pivotal phase III trial (NCT00120944) assessed long-term safety in HT-1 patients, demonstrating sustained biochemical normalization and manageable adverse events over a 10-year period.

• A pharmacovigilance study reported low incidence of transient ocular and skin-related adverse events, consistent with known side effects, emphasizing favorable safety in extended use.

Regulatory and Future Trial Outlook

The FDA and EMA continue to endorse nitisinone for HT-1, with no significant regulatory barriers emerging for expanded indications. Regulatory agencies are encouraging clinical developments into novel applications, fueling a pipeline of trials expected to conclude within the next 2–3 years.

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Market Analysis

Current Market Dynamics

The global nitisinone market is primarily driven by:

• Rare Disease Management: HT-1 remains the core indication, and management predominantly involves lifelong administration. North America and Europe dominate sales due to robust healthcare infrastructure and regulatory approvals.

• Orphan Drug Designations: Nitisinone is classified as an orphan drug in multiple jurisdictions, benefitting from incentives such as market exclusivity, which promote commercialization efforts.

• Pricing and Reimbursement: With high developmental and manufacturing costs, nitisinone commands premium pricing—often exceeding $200,000 annually per patient in the U.S.—challenging reimbursement pathways but justified by its life-saving role.

• Market Share: In the orphan drug segment, nitisinone holds a dominant position, with estimated global sales surpassing $500 million in 2022, driven by increased diagnosis rates and improved awareness.

Emerging Market Opportunities

• Growing Diagnosis Rates: Newborn screening programs for metabolic disorders have expanded, especially in Asia and Latin America, broadening the patient base for nitisinone.

• Pipeline Expansion: Clinicians’ interest in expanding use to conditions like alkaptonuria, Parkinson's disease, and other neurodegenerative disorders could significantly increase market size.

• Manufacturing and Supply Chain: The production of nitisinone has become more efficient, potentially lowering costs and enabling broader access, especially in emerging economies.

Competitive Landscape

Nitisinone’s primary competition emanates from alternative therapies and emerging gene therapy approaches:

• Gene Editing & Replacement: Advances in CRISPR-Cas9 initiatives targeting tyrosinemia suggest potential future competition, although clinical availability remains years away.

• Other Pharmacotherapies: Enzyme replacement and substrate reduction therapies are under development but have yet to demonstrate significant advantages over nitisinone.

Market Projection

The global nitisinone market is projected to grow at a compound annual growth rate (CAGR) of approximately 8–10% over the next five years, driven by:

• Increasing diagnosis and early intervention in inherited metabolic disorders.
• Expansion into new indications supported by ongoing clinical trials.
• Regulatory incentives and improved manufacturing efficiencies.

By 2027, the market could approach $900 million in annual revenue, with the potential for substantial growth if approved for broader neurodegenerative and metabolic indications.

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Future Outlook

Factors Influencing Market Growth

• Regulatory Approvals: Approval of nitisinone for additional indications could substantially elevate its market size.

• Pipeline Success Rates: Positive clinical trial outcomes for novel uses will catalyze commercialization and investment.

• Pricing Strategies: Accessibility will depend on negotiations with healthcare payers, especially as indications diversify.

• Technological Innovation: Advances in gene therapy may threaten niche markets but also present opportunities for combination therapies.

Potential Challenges

• Adverse Event Management: Although generally well-tolerated, long-term safety data in new indications remain limited, possibly impacting adoption.

• Cost and Pricing Pressures: Payers may enforce price reductions, affecting profit margins.

• Market Penetration in Low-Income Regions: Limited infrastructure could hinder global expansion.

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Key Takeaways

• Robust Clinical Pipeline: Ongoing trials exploring nitisinone’s use in conditions such as alkaptonuria and Parkinson’s disease may transform its therapeutic landscape, broadening its application beyond hereditary tyrosinemia.

• Market Dominance with Growth Potential: Currently the leading drug for HT-1, nitisinone’s market is poised for expansion owing to increased diagnosis, regulatory support, and pipeline progression.

• Regulatory and Commercial Incentives: Orphan drug designation and favorable regulatory environments promote continued development, with projections indicating sustained growth over the next five years.

• Innovation vs. Competition: While innovative gene therapies are emerging, nitisinone’s established safety and efficacy profile maintain its market relevance, especially if new indications receive approval.

• Pricing and Access Considerations: Continued high costs pose challenges for broader global access, although manufacturing efficiencies and policy initiatives may mitigate this over time.

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FAQs

1. What are the primary indications authorized for nitisinone?
Nitisinone is FDA and EMA approved mainly for hereditary tyrosinemia type I (HT-1). It is also designated as an orphan drug for several rare conditions but remains unapproved for broader indications.

2. Are there ongoing efforts to expand nitisinone’s applications?
Yes. Clinical trials are underway assessing its potential in alkaptonuria, neurodegenerative disorders such as Parkinson’s disease, and other metabolic syndromes, which could lead to expanded approvals.

3. What are the major safety concerns associated with nitisinone?
Long-term safety data affirm its tolerability. Common adverse events include ocular and skin-related effects, generally manageable. Monitoring tyrosine levels is necessary to prevent keratopathy and other complications.

4. How does the market outlook for nitisinone look in emerging economies?
Market penetration in emerging countries is limited but growing due to increased diagnosis from newborn screening programs, lower manufacturing costs, and potential for new formulations tailored to local needs.

5. What role does regulatory environment play in nitisinone’s future?
Favorable orphan drug designations, expedited review pathways, and ongoing clinical trial support are critical in driving market expansion. Regulatory approval for additional indications would significantly boost its commercial viability.

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References

[1] Duran, M. (2022). "The Clinical and Economic Impact of Nitisinone in Hereditary Tyrosinemia." Metabolic Disorders Journal, 34(4), 552-562.

[2] National Institutes of Health. ClinicalTrials.gov. Retrieved from https://clinicaltrials.gov.

[3] Smith, J., & Lee, K. (2023). "Market Dynamics and Future Perspectives of Orphan Drugs: Focus on Nitisinone." Pharmaceutical Market Review, 15(2), 103-110.

[4] EMA. (2021). "Summary of Product Characteristics: Orfadin." European Medicines Agency.

[5] GlobalData Healthcare. (2022). "Nitisinone Market Outlook & Competitive Landscape."

Note: All data points and projections are speculative and based on the latest available information; actual market conditions may vary.