Sentynl Therapeutics Announces First Comprehensive Body of Clinical Evidence Supporting NULIBRY® (fosdenopterin) in Treating Molybdenum Cofactor Deficiency Type A Compared to Natural History

Manuscript in the Journal of Inherited Metabolic Disease indicates increased survival in patients treated with fosdenopterin

SOLANA BEACH, Calif., April 2, 2025 /PRNewswire/ -- Sentynl Therapeutics, Inc. ("Sentynl"), a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences, Ltd. ("Zydus Group"), is pleased to announce the publication of NULIBRY's three clinical studies comparing the treatment effect of NULIBRY versus a natural history study in the Journal of Inherited Metabolic Disease. Fosdenopterin gained its approval by the United States Food and Drug Administration (FDA) in February 2021, the Israeli Ministry of Health (MoH) in July 2022, the European Medicines Agency (EMA) in September 2022, and the Medicines and Healthcare products Regulatory Agency (MHRA) in April 2024 for the treatment of MoCD Type A.

These data represent the first comprehensive body of clinical research in the only approved treatment for MoCD Type A patients, as well as the most abundant findings on the natural progression of the disease. The results showed statistically significant prolonged survival in treated versus untreated patients, as well as genotype-match controls with the risk of death at 5.1 times higher in the untreated patients (Cox proportional hazards 5.1; 95% CI 1.32-19.36; p=0.01). Additionally, significant improvements were seen in cognitive and motor functioning in the treated versus the untreated patients.

Fosdenopterin-treated patients experienced mild to moderate treatment emergent adverse events with the most common adverse events being catheter-related complications and infections. There were no discontinuations or dose modifications due to adverse events.

MoCD Type A is an ultra-rare, autosomal recessive disease caused by variants in the MOCS1 gene. It typically presents at birth or shortly thereafter and if left untreated causes rapid, irreversible neurogeneration due to a build up of toxic sulfite levels in the brain, and ultimately a premature death. Fosdenopterin, a synthetic form of cPMP, restores normal sulfite levels thereby reducing the toxic sulfite concentration. 

"This publication marks the end of a truly collaborative and enthusiastic path from basic research to the bedside that started 21 years ago, when we reported the successful treatment of a mouse model of MoCD type A with cPMP (cyclic pyranopterin monophosphate, fodenopterin)," said Guenter Schwarz, Professor, Institute of Biochemistry, Department of Chemistry and Biochemistry & Center for Molecular Medicine, Cologne University, Germany. "Increased awareness and expeditious testing upon suspicion of MoCD are critical to improve neurological outcomes and overall survival in patients with MoCD Type A who can be treated early with fosdenopterin."

"It is important that clinicians consider the diagnosis of MoCD type A in neonates with intractable seizures, encephalopathy, feeding difficulties or increased startle response as earlier treatment appeared to improve achievement of developmental milestones," said Liza Squires, MD, Sentynl Medical Consultant.

Sentynl Therapeutics is committed to treating rare genetic diseases, which often present in infancy and early childhood.  "The publication of these data in JIMD is a huge milestone for MoCD Type A patients, caregivers, and the medical community," said Matt Heck, CEO, Sentynl. "It is the culmination of four companies' commitment in NULIBRY's clinical development program spanning over two decades."

About Molybdenum Cofactor Deficiency (MoCD) Type A
MoCD Type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production, leading to a lack of molybdenum-dependent enzyme activity.^1,2 The lack of activity leads to decreased sulfite oxidase activity with buildup of sulfite and secondary metabolites (such as S-sulfocysteine) in the brain, which causes irreversible neurological damage.²

MoCD Type A is an ultra-rare disease. The incidence and prevalence of MoCD Type A in the United States are not known, but the estimated incidence is 1 per 342,000 to 411,000 live births (0.24 and 0.29 per 100,000).³ Based on these estimates, MoCD Type A is likely to be underdiagnosed.

The most common presenting symptoms of MoCD Type A are seizures, feeding difficulties and encephalopathy. Patients with MoCD Type A who survive beyond infancy typically suffer from progressive brain damage, which presents in characteristic patterns on magnetic resonance imaging (MRI). This damage leads to severe psychomotor impairment and an inability to make coordinated movements or communicate with their environment.

1. Mechler K et al. Genet Med. 2015;17(12):965-970.
2. Veldman A et al. Pediatrics. 2010;125(5):e1249-e1254
3. Mayr SJ, et al. Forecasting the incidence of rare diseases: an iterative computational and biochemical approach in molybdenum cofactor deficiency type A. Presented at the 2019 SSIEM meeting; September 3-6, 2019; Rotterdam, The Netherlands.

About NULIBRY^® (fosdenopterin) for Injection
NULIBRY (fosdenopterin) for Injection is a substrate replacement therapy that provides a synthetic source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase, an enzyme that reduces levels of neurotoxic sulfites. NULIBRY was approved by the U.S. FDA in February 2021, and by the Israel Ministry of Health in July 2022 and is indicated to reduce the risk of mortality in patients with MoCD Type A. NULIBRY was also approved by the EMA in September 2022, with an indication for treatment of patients with MoCD Type A.

Important Safety Information

Warnings and Precautions

Potential for Photosensitivity

NULIBRY can make the patient oversensitive to sunlight. NULIBRY-treated patients or their caregivers are advised to avoid or minimize patient exposure to sunlight and artificial UV light and adopt precautionary measures when exposed to the sun, including wearing protective clothing and sunglasses, and use broad-spectrum sunscreen with high SPF in patients 6 months of age and older. If photosensitivity occurs, caregivers/patients are advised to seek medical attention immediately and consider a dermatological evaluation.

Adverse Reactions

The most common adverse reactions in NULIBRY-treated patients were infusion catheter–related complications (89%), pyrexia (fever) (78%), viral infection (56%), pneumonia (44%), otitis media (ear infection) (44%), vomiting (44%), cough/sneezing (44%), viral upper respiratory infection (33%), gastroenteritis (33%), diarrhea (33%) , and bacteremia (33%). Adverse reactions for rcPMP-treated patients were similar to the NULIBRY-treated patients.

Patient Counseling Information

Please read the FDA-approved NULIBRY Prescribing Information and Instructions for Use and follow the instructions on how to prepare and administer NULIBRY.

NULIBRY has a potential for photosensitivity; see Warnings and Precautions. Seek medical attention immediately if the patient develops a rash or if they notice symptoms of photosensitivity reactions (redness, burning sensation of the skin, blisters).

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

About Sentynl Therapeutics
Sentynl Therapeutics, Inc. ("Sentynl") is a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. The company was acquired by the Zydus Group in 2017. Sentynl's experienced management team has previously built multiple successful pharmaceutical companies. With a focus on commercialization, Sentynl looks to source effective and well-differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is dedicated to ensuring no patient is overlooked, and is committed to the highest ethical standards and compliance with all applicable laws, regulations and industry guidelines. For more information, visit https://sentynl.com.

About Zydus Group
Zydus Lifesciences Ltd. with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global life sciences company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group employs over 27,000 people worldwide, including 1,400 scientists engaged in R & D, and is driven by its mission to unlock new possibilities in life sciences through quality healthcare solutions that impact lives. The group aspires to transform lives through path-breaking discoveries. For more information, visit https://www.zyduslife.com/zyduslife.

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SOURCE Sentynl Therapeutics