A Prospective, Non-interventional, Post-Marketing Study to Describe Outcome of Nitisinone Treatment in Hereditary Tyrosinemia Type 1 (HT-1) Patients in Routine Clinical Care in China

This is a prospective, non-interventional, non-comparative, multicenter study to collect data on HT-1 patients in China treated with Nitisinone in a routine clinical setting. No tests or examinations are mandated in the study.

Start Date01 Sep 2025

Sponsor / Collaborator

Swedish Orphan Biovitrum AB

CTRI/2024/03/063760

/ Not yet recruitingPhase 3IIT

Prospective, Randomised, Double blind, Parallel-group Study to Assess the Safety and efficacy of 2/5mg Once Daily Nitisinone among Indian Patients with Alkaptonuria – A randomised control trial. - Nil

Start Date25 Mar 2024

Sponsor / Collaborator

Indian Council of Medical Research

CTRI/2023/05/052626

/ Not yet recruitingNot ApplicableIIT

Pharmacokinetic and Dynamic Correlation for optimum therapy of NTBC for the Treatment of Indian Patients with Hereditary Tyrosinemia Type 1

Start Date15 May 2023

Sponsor / Collaborator-

100 Clinical Results associated with Nitisinone

100 Translational Medicine associated with Nitisinone

100 Patents (Medical) associated with Nitisinone

493

Literatures (Medical) associated with Nitisinone

01 Jul 2025·INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY

Killing of Anopheles stephensi mosquitoes by selective triketone inhibitors of 4-hydroxyphenylpyruvate dioxygenase depends on a high protein meal

Article

Author: Hartmann, David ; Dechering, Koen J ; Valdés, James J ; Sheshachalam, Avinash ; Kučera, Matěj ; Perner, Jan ; Vlot, Marnix ; Palusová, Adéla ; Vos, Martijn W

The malaria vector Anopheles stephensi has expanded from Asia into Eastern Africa, posing a growing global health threat due to its adaptive biology and increasing resistance to conventional control methods. Here, we characterise 4-hydroxyphenylpyruvate dioxygenase (HPPD), a crucial enzyme in the tyrosine degradation pathway, and demonstrate its potential as a novel drug target in An. stephensi. Homology modeling combined with molecular dynamics simulations confirmed that key inhibitor-binding residues are highly conserved across mosquito HPPDs and predicted potent inhibition by triketone-based compounds. Using cell-based assay with codon-optimized recombinant expression in Escherichia coli, we screened several triketone and diketonitrile HPPD inhibitors and identified nitisinone as the most potent inhibitor, displaying nanomolar-range IC₅₀ values. Membrane feeding assays showed that nitisinone's insecticidal activity relies on ingestion of a high-protein meal, with haemoglobin identified as the potent dietary factor driving toxicity. These results highlight HPPD inhibition as a promising blood-meal-dependent vector control strategy specifically targeting haematophagous mosquitoes.

01 Jun 2025·PEDIATRIC NEPHROLOGY

Diagnosing alkaptonuria-related nephropathy with urine albumin analysis

Article

Author: Gülbahçe, Aliye ; Muderrisoglu, Ahmet

Abstract:

Homogentisic acid (HGA) accumulation in alkaptonuria (AKU) causes injuries in various organs including the kidney. We present a case of a 9-year-old girl initially diagnosed with AKU-related nephropathy due to proteinuria found in her urine analyses. Despite 1 month of ramipril treatment, the patient’s proteinuria progressed, and as a result, kidney biopsy and nitisinone treatment were planned. In addition, we controlled her proteinuria with urine albumin measurement. After finding a normal urine albumin level in the 24-h urine sample, we realized that the patient was misdiagnosed with proteinuria because of HGA interference with urine protein level measurement using benzethonium. The patient’s treatment for kidney injury was canceled. Urine albumin level was measured as normal 2 months later, confirming proteinuria was a false-positive test result. AKU-related nephropathy should be evaluated with urine albumin measurement instead of protein. In this way, the complication risk of unnecessary interventions and pharmacotherapies can be avoided.

01 Jun 2025·JOURNAL OF ANATOMY

An anatomical investigation of alkaptonuria: Novel insights into ochronosis of cartilage and bone

Article

Author: Ranganath, Lakshminarayan R. ; Gallagher, James A. ; Tierney, Claire M. ; Rothwell, Paul D. ; Prior, Amanda ; Thomas, Neil P. ; Charlesworth, Gemma ; Hughes, Juliette H. ; Bond, Alistair P.

Abstract:

Ochronotic pigmentation of connective tissue is the central pathological process in the rare metabolic disease alkaptonuria (AKU). Tissue pigmentation in AKU occurs due to unmetabolised homogentisic acid (HGA) in the circulation, caused by an enzyme deficiency in the liver. Ochronotic pigmentation, derived from HGA, has previously been reported and described in large joints obtained from arthroplasty surgeries, which typically have advanced disease. Many tissues that are affected by ochronosis are not accessible for study during life, including tissues subjected to early and mid‐stage disease. Here, the opportunity arose to anatomically examine a 60‐year‐old AKU female body donor, allowing the investigation of previously understudied tissue, including those undergoing early‐stage pathological changes. Dissection of fresh‐frozen tissue was carried out and harvested tissues were fixed and examined histologically using H&E and Schmorl's stains to aid identification of ochronotic pigment. This work focusses on osteochondral tissues including extra‐skeletal cartilage, viscera and eyes. Gross and histological images demonstrating pigmentation in the cartilage and perichondrium of the ear ossicles, tympanic membrane and the pubic symphysis fibrocartilaginous disc are described for the first time here. We also show the first examination of the temporomandibular joint, which macroscopically appeared unpigmented, with histological analysis of the fibrocartilaginous disc showing no pigmentation. Pigmentation of non‐articular hyaline cartilage was observed in the respiratory tract, in both the hyaline cartilage and perichondrium, confirming previous findings. Within smaller joints, pigmentation of chondrons and the surrounding territorial matrix was observed, but was confined to calcified articular cartilage, and was not generally found in the hyaline articular cartilage. Dark pigmentation of the perichondrium adjacent to the articular surface was observed in numerous small joints. The calcified bone matrix was not pigmented but ochronosis was identified in a small fraction of trabecular osteocytes in the capitate and radius, with substantially more pigmented osteocytes observed in bone of the ear ossicles. Viscera examined were unpigmented. This anatomical examination of tissues from an AKU individual highlights that most osteochondral tissues are susceptible to HGA‐derived pigmentation, including the ear ossicles which are the smallest bones in the body. Within joints, calcified cartilage and perichondrium appear to be the earliest affected tissues, but why this is the case is not understood. Furthermore, why the TMJ disc was unaffected by pigmentation is intriguing. The heterogenous appearance of pigmentation both within and between different tissues indicates that factors other than tissue type (i.e. cartilage, perichondrium) and matrix composition (i.e. collagen‐rich, calcified) may affect the process of ochronosis, such as oxygen tension, loading patterns and tissue turnover. The effect of nitisinone treatment on the ochronotic disease state is considered, in this case 7 years of treatment, however comparisons could not be made to other cases due to inter‐individual variability.

News (Medical) associated with Nitisinone

07 Aug 2025

·ir.etonpharma.com

Eton Pharmaceuticals Reports Second Quarter 2025 Financial Results

Q2 2025 product sales of $18.9 million , representing 108% growth over Q2 2024 and the 18th straight quarter of sequential product sales growth Q2 2025 basic and fully diluted GAAP EPS of $(0.10) , non-GAAP fully diluted EPS of $0.03 , and Adjusted EBITDA of $3.1 million Launched KHINDIVI™ (hydrocortisone) Oral Solution Reached 100 active INCRELEX® patients, ahead of previous guidance of year end Company projects reaching an annual revenue run rate of $80 million in Q3, one quarter ahead of previous guidance Management to hold conference call today at 4:30pm ET DEER PARK, Ill. , Aug. 07, 2025 (GLOBE NEWSWIRE) -- Eton Pharmaceuticals, Inc (“Eton” or “the Company”) (Nasdaq: ETON), an innovative pharmaceutical company focused on developing and commercializing treatments for rare diseases, today reported financial results for the quarter ended June 30, 2025 . “Eton continues to execute on all fronts. During the second quarter, we received FDA approval for and subsequently launched KHINDIVI, marking our third commercial launch in 2025. As the first and only FDA-approved oral solution of hydrocortisone, KHINDIVI is a game changer for many pediatric patients. We were excited to finally bring this important treatment to the market and look forward to continuing to raise awareness of its availability,” said Sean Brynjelsen , CEO of Eton Pharmaceuticals . “Our strong commercial execution helped us deliver an impressive 108% revenue growth in the quarter, driven primarily by ongoing growth from ALKINDI SPRINKLE and the relaunches of INCRELEX and GALZIN. INCRELEX continues to track well ahead of our original expectations with 100 active patients at the end of July. We previously expected to reach this mark at the end of the year, so we are proud of the team’s hard work to hit this milestone well ahead of schedule. With these recent successes and the ongoing strength of our entire portfolio, we now expect to achieve an $80 million annual revenue run rate in the third quarter, one quarter ahead of our prior projections.” “In addition to executing on these three product launches and driving significant revenue growth, we continue to advance our pipeline programs, evaluate new business development opportunities and prepare for the potential approval and launch of ET-600 in the first quarter of 2026,” concluded Brynjelsen. Second Quarter and Recent Business Highlights 18th straight quarter of sequential growth in product sales and 108% growth over prior year quarter. Eton reported second quarter 2025 product sales of $18.9 million . Year-over-year revenue growth was driven primarily by continued growth in ALKINDI SPRINKLE® and the addition of revenues from INCRELEX and GALZIN. INCRELEX relaunch outperforming expectations; reached 100 active patients at the end of July. Eton’s ongoing engagement with the pediatric endocrinology community has helped drive awareness and clinical adoption of INCRELEX. The Company had a robust presence at key scientific conferences during the quarter, including Pediatric Endocrine Nurses Society (PENS), Pediatric Endocrine Society (PES), and Endocrine Society (ENDO), where it met with multiple advisory boards and Key Opinion Leaders, participated in a product symposium, hosted exhibit booths, and presented a new scientific poster featuring real-world registry data demonstrating the efficacy and safety of INCRELEX. Due to the strong execution of Eton’s commercial organization, INCRELEX has grown from 67 active patients in December 2024 to 100 active patients at the end of July, a target the Company initially expected to reach at the end of 2025. FDA approval and commercial launch of KHINDIVI, Eton’s 8th commercial product. On May 28th , Eton received FDA approval for KHINDIVI as a replacement therapy in pediatric patients five years of age and older with adrenocortical insufficiency. The product became commercially available in June, and the Company has received favorable early feedback from patients and prescribers. Eton is also working to develop a new formulation for patients aged four years and under. Eton has already manufactured registration batches of a new KHINDIVI formulation with substantially reduced levels of the inactive ingredients polyethylene glycol 400, propylene glycol, and glycerin, which Eton believes will allow for an expansion of the product’s approved population age. A pre-submission meeting with the FDA is scheduled for September, and the Company expects to file a supplement to the existing KHINDIVI New Drug Application (NDA) in the first half of 2026, which could allow for approval before the end of 2026. Continued growth of ALKINDI SPRINKLE. In the second quarter, ALKINDI SPRINKLE delivered strong sequential and year-over-year growth in revenue and patients on treatment. Through the second quarter, year-to-date new patient prescriptions exceeded the first two quarters of all prior years. In recent months, Eton had a prominent footprint at major healthcare professional congresses such as PENS, PES, ENDO, and Pediatric Endocrinology Society of Texas , Oklahoma , Louisiana , Arkansas (PESTOL), where the Company presented a new scientific poster showcasing real-world ALKINDI SPRINKLE safety and adherence data. Strong initial trajectory for GALZIN commercial relaunch. Eton relaunched GALZIN in March and believes it has now successfully transitioned most existing users to Eton’s distribution network. The Company’s launch has been well received by the Wilson disease community, which has expressed excitement about Eton’s efforts to broaden access to treatment with its $0 copay for eligible patients and high-touch specialty pharmacy distribution to help support medication adherence. The Company sees a significant long-term growth opportunity and has launched awareness and educational campaigns to target patients that have historically used over-the-counter zinc supplement products that are not FDA-approved for Wilson disease. NDA for ET-600 accepted by the FDA and second patent received. In July, ET-600's NDA was accepted for review by the FDA and assigned a Target Action Date of February 25, 2026 . Commercialization activities are already underway in anticipation of a potential first quarter 2026 launch. Also in July, the United States Patent and Trademark Office (USPTO) granted the Company a second patent covering ET-600's proprietary formulation of desmopressin oral solution. The patent expires in 2044 and is expected to be listed in the FDA Orange Book upon the product’s approval. Second Quarter Financial Results Net Revenue: Net revenues for the second quarter of 2025 were $18.9 million compared with $9.1 million in the prior year period, an increase of 108%. The growth was driven primarily by increased sales of ALKINDI SPRINKLE and the addition of sales from INCRELEX and GALZIN. The company now expects to achieve an approximately $80 million annual revenue run rate in the third quarter of 2025, one quarter ahead of previous projections. Gross Profit: Gross profit for the second quarter of 2025 was $11.9 million compared with $5.6 million in the prior year period, an increase of 112%. Adjusted gross profit, which adjusts for the impact of acquired inventory step-up adjustments and intangible amortization, was $14.1 million in the second quarter of 2025, representing an adjusted gross margin of 75% compared to adjusted gross profit of $5.9 million and adjusted gross margin of 65% in the prior year period. The margin improvement was primarily driven by continued growth of higher-margin ALKINDI SPRINKLE and the addition of high margin INCRELEX revenue. The Company continues to expect to report full year 2025 adjusted gross profit of approximately 70%. Research and Development (R&D) Expenses: R&D expenses for the second quarter of 2025 were $3.7 million compared to $3.0 million in the prior year period. R&D expenses for the second quarter of 2025 included a $2.2 million expense for the FDA application fee associated with the submission of the Company’s NDA for ET-600 and a $0.5 million expense related to the licensing of AMGLIDIA®.General and Administrative (G&A) Expenses: G&A expenses for the second quarter of 2025 were $9.7 million compared to $5.6 million in the prior year period. The increase was primarily attributable to an increase in sales and marketing expenses associated with the ongoing product launches and an increase in compensation and benefit expenses due to an increase in general and administrative headcount. Adjusted G&A expense, which removes share-based compensation, transaction related costs, and other one-time expenses, was $7.6 million in the quarter, compared with $4.9 million the prior year period. The Company expects Adjusted G&A expenses to remain flat or decline through the second half of 2025. Adjusted Earnings Before Interest, Taxes, Depreciation and Amortization (Adjusted EBITDA): Adjusted EBITDA for the second quarter of 2025 was $3.1 million compared to $(1.6) million in the prior year period. Net Income/Loss: Net loss for the second quarter of 2025 was $2.6 million or $0.10 per basic and diluted share compared to a net loss of $3.0 million or $0.12 per basic and diluted share in the prior year period. On a non-GAAP basis, the Company reported net income of $1.5 million or $0.03 per diluted share, for the second quarter of 2025 compared to a net loss of $1.9 million , or $0.08 per diluted share in the prior year period. For a reconciliation of GAAP net loss to Earnings Before Interest, Taxes, Depreciation and Amortization EBITDA (“EBITDA”), Adjusted EBITDA and adjusted Non-GAAP basic and fully diluted earnings per share to the most directly comparable GAAP financial measure, please see the tables below. Cash Position: As of June 30, 2025 , the Company had cash and cash equivalents of $25.4 million and generated $8.0 million of operating cash flow during the quarter. Subsequent to the second quarter, Eton received a $4.6 cash payment for the INCRELEX ex- U.S. licensing agreement executed in the first quarter. Conference Call and Webcast Information As previously announced, Eton Pharmaceuticals will host its second quarter 2025 conference call as follows: In addition to taking live questions from participants on the conference call, management will be answering emailed questions from investors. Investors can email questions to: investorrelations@etonpharma.com. The live webcast can be accessed on the Investors section of Eton’s website at https://ir.etonpharma.com. An archived webcast will be available on Eton’s website approximately two hours after the completion of the event and for 30 days thereafter. About Eton Pharmaceuticals Eton is an innovative pharmaceutical company focused on developing and commercializing treatments for rare diseases. The Company currently has eight commercial rare disease products: KHINDIVI™, INCRELEX®, ALKINDI SPRINKLE®, GALZIN®, PKU GOLIKE®, Carglumic Acid, Betaine Anhydrous, and Nitisinone. The Company has five additional product candidates in late-stage development: ET-600, Amglidia®, ET- 700, ET -800 and ZENEO® hydrocortisone autoinjector. For more information, please visit our website at www.etonpharma.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the expected ability of Eton to undertake certain activities and accomplish certain goals and objectives. These statements include but are not limited to statements regarding Eton’s business strategy, Eton’s plans to develop and commercialize its product candidates, the safety and efficacy of Eton’s product candidates, Eton’s plans and expected timing with respect to regulatory filings and approvals, and the size and growth potential of the markets for Eton’s product candidates. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Eton’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. These and other risks concerning Eton’s development programs and financial position are described in additional detail in Eton’s filings with the Securities and Exchange Commission . All forward-looking statements contained in this press release speak only as of the date on which they were made. Eton undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Non-GAAP Financial Measures In addition to the Company’s results of operations determined in accordance with U.S. generally accepted accounting principles (GAAP), which are presented and discussed above, management also utilizes Adjusted EBITDA, an unaudited financial measure that is not calculated in accordance with GAAP, to evaluate the Company’s financial results and performance and to plan and forecast future periods. Adjusted EBITDA is considered a “non-GAAP” financial measure within the meaning of Regulation G promulgated by the SEC . Management believes that this non-GAAP financial measure reflects an additional way of viewing aspects of the Company’s operations that, when viewed with GAAP results, provides a more complete understanding of the Company’s results of operations and the factors and trends affecting its business. Management believes Adjusted EBITDA provides meaningful supplemental information regarding the Company’s performance because (i) it allows for greater transparency with respect to key metrics used by management in its financial and operational decision-making; (ii) it excludes the impact of non-cash or, when specified, non-recurring items that are not directly attributable to the Company’s core operating performance and that may obscure trends in the Company’s core operating performance; and (iii) it is used by institutional investors and the analyst community to help analyze the Company’s results. However, Adjusted EBITDA and any other non-GAAP financial measures should be considered as a supplement to, and not as a substitute for, or superior to, the corresponding measures calculated in accordance with GAAP. Further, non-GAAP financial measures used by the Company and the way they are calculated may differ from the non-GAAP financial measures or the calculations of the same non-GAAP financial measures used by other companies, including the Company’s competitors. Adjusted EBITDAThe Company defines Adjusted EBITDA as net loss, excluding the effects of stock-based compensation and expenses, interest, taxes, depreciation, amortization, investment loss, net, and, if any and when specified, other non-recurring income or expense items. Management believes that the most directly comparable GAAP financial measure to Adjusted EBITDA is net loss. Adjusted EBITDA has limitations and should not be considered as an alternative to gross profit or net loss as a measure of operating performance or to net cash provided by (used in) operating, investing, or financing activities as a measure of ability to meet cash needs. Investor Relations: Lisa M. Wilson , In-Site Communications, Inc. T: 212-452-2793 E: lwilson@insitecony.com Source: Eton Pharmaceuticals

Drug ApprovalFinancial StatementNDA

21 Jul 2025

·www.businesswire.com

Cycle Pharmaceuticals Selects LeMed Specialty Pharmacy as Exclusive U.S. Specialty Pharmacy Distribution and Services Partner for HARLIKU™ (nitisinone) Tablets — the First and only FDA-approved Treatment for Adult Patients with Alkaptonuria (AKU)

BRONX, N.Y.--(BUSINESS WIRE)--Cycle Pharmaceuticals today announced they have awarded LeMed Specialty Pharmacy the exclusive contract for specialty pharmacy distribution and services for HARLIKU™ (nitisinone) Tablets, the first and only FDA-approved treatment for use in alkaptonuria (AKU). LeMed will manage commercial and non-commercial dispensing for HARLIKU across the United States (US). “Together, we remain dedicated to putting patients first— ensuring those living with AKU receive the support and treatment they need, now and into the future.” “We’re excited to extend our partnership with LeMed Specialty Pharmacy, building on years of successful collaboration across rare diseases. Together, we remain dedicated to putting patients first— ensuring those living with AKU receive the support and treatment they need, now and into the future.” – Chikai Lai, SVP & CCO, Cycle Pharmaceuticals LeMed’s rare disease focus includes operating within ultra-limited and exclusive distribution networks - experience that translates into operational agility and true collaboration with biopharma innovators. The expanding partnership between Cycle and LeMed already supports patients living with hereditary angioedema (HAE), phenylketonuria (PKU), and primary periodic paralysis (PPP). “We are honored Cycle chose LeMed to ensure every eligible AKU patient gets timely access to HARLIKU,” said Nathaniel Keifer, Vice President, Client Strategy at LeMed Specialty Pharmacy. “Our one-size-fits-one bespoke model pairs clinical excellence and a patient-experience mindset with real-time data insights and an agile infrastructure, enabling Cycle to monitor outcomes and scale when necessary while patients experience the speed to therapy and support they deserve.” With the FDA’s approval of HARLIKU, patients living with AKU in the US now have the option of treatment, guidance and care tailored towards their unique needs. Patients and providers can look forward to working with LeMed Specialty Pharmacy when it comes time to dispense an eagerly awaited treatment. About HARLIKU™ (nitisinone) HARLIKU is the first and only FDA-approved treatment for reducing urinary homogentisic acid (HGA) in adults with Alkaptonuria (AKU). By inhibiting an upstream enzyme, HARLIKU can lower urinary HGA production by up to 97%.¹ Clinical data have shown that treatment with HARLIKU can lead to significant improvements in pain, energy levels, and physical functioning.² To assist patients throughout their treatment journey, HARLIKU is also accompanied with Cycle Vita™ - providing patients with individualized support* from onboarding to continuous product and clinical support. About LeMed Specialty Pharmacy LeMed Specialty Pharmacy is an independent, national specialty pharmacy headquartered in the Bronx, New York, proud of our 20+ year history of shaping the future of healthcare. With no private-equity investment and no PBM affiliation, LeMed is one of the last truly independent specialty pharmacies dedicated to orphan therapies and serving the people living with rare diseases that they treat. Supported by fully redundant, bi-coastal sites in New York and Arizona, LeMed holds dual-specialty accreditations, offers both commercial and non-commercial dispensing, and is licensed to ship to all 50 states and Puerto Rico while delivering industry-leading patient-satisfaction scores and an agile, data-driven, patient-first team that partners with biopharmaceutical manufacturers, patients, and payers to create bespoke programs that innovate the patient experience and drive measurable outcomes. Learn more at www.lemedrx.com About Cycle Pharmaceuticals Cycle Pharmaceuticals was founded in 2012 with the sole aim of delivering drug treatments and product support to the underserved rare disease patient community. Cycle Pharma focuses on rare genetic conditions in metabolic, immunology, urology, and oncology, as well as neurology, where we focus on multiple sclerosis. Cycle Pharma is headquartered in Cambridge, UK and has offices in Boston, Massachusetts. For more information, please visit www.cyclepharma.com and follow us on X, LinkedIn and Facebook.

Drug ApprovalLicense out/in

17 Jul 2025

·www.businesswire.com

Cycle Pharmaceuticals launches HARLIKU™ (nitisinone) Tablets, the first FDA-approved treatment for use in Alkaptonuria (AKU)

BOSTON--(BUSINESS WIRE)--Cycle Pharmaceuticals announced the launch of HARLIKU, the first and only FDA-approved treatment for reducing urinary homogentisic acid (HGA) in adult patients with alkaptonuria (AKU).1 AKU, also known as Black Bone Disease, is an ultra-rare genetic metabolic disorder that affects approximately one in 1,000,000 people in the US.2 HARLIKU can reduce urinary HGA production by up to 97% through the inhibition of an upstream enzyme.1 Clinical data demonstrated that nitisinone-treated patients experienced significant improvement in pain, energy levels, and physical functioning.3 With the launch of HARLIKU, patients now have the option of treatment, guidance and care tailored to the unique needs of AKU. Accompanied by our dedicated support program, Cycle Vita™, patients will receive individualized support* from onboarding to continuous product and clinical support throughout treatment. “AKU is an ultra-rare condition with slow progression and variable presentation, which makes diagnosis and accessing appropriate care difficult.2, 4 With the launch of HARLIKU, Cycle Vita can now provide patients with AKU the individualized support they need to navigate their treatment from diagnosis onwards.” – Jamie Ray, Director – Patient Support Program, Cycle Pharmaceuticals “The launch of HARLIKU marks an exciting milestone for our AKU community. As the first commercially available treatment for AKU in the United States, it will empower patients to take a more proactive role in their care, paving the way for personalized treatment discussions and helping to reduce barriers to access.” - Nick Sireau, CEO and Chair of Trustees, AKU Society Indications HARLIKU™ is indicated for the reduction of urine homogentisic acid (HGA) in adult patients with alkaptonuria (AKU). Important Safety Information Do not prescribe HARLIKU to patients allergic to nitisinone or any other contained ingredients. Warnings and Precautions: Ocular Symptoms and Hyperkeratotic Plaques Due to Elevated Plasma Tyrosine Level: Ocular signs and symptoms including keratitis, corneal opacities, corneal irritation, corneal ulcers, conjunctivitis, eye pain, and photophobia, have been reported in patients. Perform slit-lamp examination prior to treatment and regularly thereafter. Reexamine patients if symptoms develop or tyrosine levels are > 500 micromole/L. Assess plasma tyrosine levels in patients with an abrupt change in neurological status. Perform a clinical laboratory assessment, including plasma tyrosine levels, in patients with an abrupt change in neurological status. Leukopenia and Severe Thrombocytopenia In clinical trials, patients with hereditary tyrosinemia type 1 (HT-1) treated with another oral formulation of nitisinone and dietary restriction developed reversible leukopenia (3%), thrombocytopenia (3%), or both (1.5%). No patients developed infections or bleeding as a result of the episodes of leukopenia and thrombocytopenia. Monitor platelet and white blood cell counts during HARLIKU therapy. Adverse Reactions: The most common adverse reactions (≥1%) reported in patients with AKU taking nitisinone in clinical trials are elevated tyrosine levels, thrombocytopenia and keratitis. Drug Interactions: Nitisinone is a moderate CYP2C9 inhibitor and a weak CYP2E1 inducer. Potential clinical impact of Harliku administration with CYP2C9 substrates. Reduce the dosage of the co-administered drugs metabolized by CYP2C9 by half. Additional dosage adjustments may be needed. Nitisinone is an inhibitor of OAT1/OAT3. Potential clinical impact of administration with OAT1/OAT3 substrates. Patients should be monitored for potential adverse reactions. Use in Specific Populations: Pregnancy: Limited available data with nitisinone use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Lactation: The developmental and health benefits of breastfeeding should be considered against the mother’s clinical need for HARLIKU, along with potential adverse effects on the breastfed infant from HARLIKU or from the underlying maternal condition. Pediatric Use: The safety and effectiveness of HARLIKU have not been established in pediatric patients with AKU. Geriatric Use: Insufficient data from clinical studies of HARLIKU to determine if patients ≥ 65 years of age respond differently. Elderly patients should be cautious reflecting any decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. For more detailed information, please refer to the full Prescribing Information at harliku.com/pi To report SUSPECTED ADVERSE REACTIONS, contact Cycle Pharmaceuticals at 1-855-831-5413, or the FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch. US-HKU-2500015 | June 2025 References HARLIKU (nitisinone) Tablets. Prescribing Information. Cycle Pharmaceuticals Ltd Introne WJ, Perry M, Chen M. 2003 (updated 2021). Alkaptonuria. Available at: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/sites/books/NBK1454/ [Accessed May 29 2025] Spears KR, Rossignol F, Perry MB, et al. 2024 Patient-reported outcomes and functional assessments of patients with Alkaptonuria in a 3-year Nitisinone treatment trial. Mol Genet Metab . 143(1-2),108562. doi:10.1016/j.ymgme.2024.108562 Zatkova, A., Ranganath, L., & Kadasi, L. 2020. Alkaptonuria: Current Perspectives. The application of clinical genetics , 13 , 37–47. doi:10.2147/TACG.S186773 *Some areas of support may not be accessible to all patients. Eligibility criteria may apply to ensure compliance with all applicable federal and state requirements, and benefits may be limited to commercially insured patients only. For more detailed information about eligibility, terms and conditions, please contact the Cycle Vita team at 888-360-8482. ©2025 Cycle Pharmaceuticals Limited. All rights reserved. HARLIKU™ and Cycle Vita™ are trademarks of Cycle Pharmaceuticals Limited in the United States. About Cycle Pharmaceuticals Cycle Pharmaceuticals was founded in 2012 with the sole aim of delivering drug treatments and product support to the underserved rare disease patient community. Cycle Pharma focuses on rare genetic conditions in metabolic, immunology, urology, and oncology, as well as neurology, where we focus on multiple sclerosis. Cycle Pharma is headquartered in Cambridge, UK and has offices in Boston, Massachusetts. For more information, please visit www.cyclepharma.com and follow us on X, LinkedIn and Facebook.

Drug Approval

100 Deals associated with Nitisinone

External Link

KEGG	Wiki	ATC	Drug Bank
D05177	Nitisinone	A16AX04	DB00348

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Alkaptonuria	European Union	Swedish Orphan Biovitrum International AB	21 Feb 2005
Alkaptonuria	Iceland	Swedish Orphan Biovitrum International AB	21 Feb 2005
Alkaptonuria	Liechtenstein	Swedish Orphan Biovitrum International AB	21 Feb 2005
Alkaptonuria	Norway	Swedish Orphan Biovitrum International AB	21 Feb 2005
Tyrosinemias	European Union	Swedish Orphan Biovitrum International AB	21 Feb 2005
Tyrosinemias	Iceland	Swedish Orphan Biovitrum International AB	21 Feb 2005
Tyrosinemias	Liechtenstein	Swedish Orphan Biovitrum International AB	21 Feb 2005
Tyrosinemias	Norway	Swedish Orphan Biovitrum International AB	21 Feb 2005
Tyrosinemia, Type I	United States	Swedish Orphan Biovitrum AB	18 Jan 2002

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00107783 (FDA_CDER) Manual	Phase 2	Alkaptonuria	40	HARLIKU 2 mg	dvlhzxczfg(ckuzcvwncs) = nzdximhknc fbhftntmau (lxoygnyfkd, -79 to -97) View more	Positive	10 Jun 2025
NCT00107783 (FDA_CDER) Manual	Phase 2	Alkaptonuria	40	No Treatment	dvlhzxczfg(ckuzcvwncs) = qagszynbsi fbhftntmau (lxoygnyfkd, 0 - +216) View more	Positive	10 Jun 2025
NCT01916382 (SONIA 2, ESC2024)	Phase 4	Aortic Valve Stenosis \| Alkaptonuria homogentisic acid levels	138	Nitisinone	hptegcgslg(eguvhgvefz) = shnrxmywfk pkwhygwxdd (pgxomsqsem, -0.054 to 0.18)	Positive	30 Aug 2024
NCT01390077 (CTgov)	Phase 2/3	Alkaptonuria	8	Nitisinone	nbdawollpz(vzbspnyegi) = gvimfqulfi raszubwrrh (cyffbvhwai, vnqqnhzrye - kvgcrswjay) View more	-	22 Apr 2021
NCT01916382 (SONIA 2, Pubmed \| Lancet Diabetes Endocrinol) Manual	Phase 3	Alkaptonuria	138	nitisinone	dpuzyyfedg(zsdxyghzkt) = vgkkozxzgx hwdlvilrjd (coiboudkxq ) View more	Positive	01 Sep 2020
	Phase 3	Alkaptonuria	138	no treatment	foxzmzlekg(qrpdwofqnf) = gynqjgqosc vnuiktonqx (jogjbjgaey )	Positive	01 Sep 2020
NCT01838655 (Pubmed \| JCI Insight)	Phase 1/2	Oculocutaneous Albinism Type 1B	5	Nitisinone 2 mg/d	rwixggpgjs(tpbugcyahm) = skdsngrznx heasxrtice (kijvyssfsg, ± 1.54) View more	-	24 Jan 2019
NCT01838655 (CTgov)	Phase 1/2	Blindness \| Oculocutaneous Albinism Type 1B	5	Nitisinone	bthzudhaqu(kbrlgkhmnz) = zobzhqudmg opfardxxwt (pbkxevidie, 1.68) View more	-	17 Nov 2017
NCT01734889 (CTgov)	Phase 1	Tyrosinemia, Type I	18	Nitisinone	lyaqwvjffj(spoetpirry) = bdkcjwtklv rforbqgnhl (xojuvopbfx, efcjnegqay - btrbghaobl) View more	-	04 Mar 2014

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