Nulibry (fosdenopterin) / BridgeBio, Zydus Lifesciences - LARVOL DELTA

Molybdenum cofactor deficiency : a single-center experience (SSIEM 2026) - "MoCD is a rare, severe neurodegenerative disorder typically presenting in the neonatal period with seizures, though later-onset forms exist. Our findings are consistent with previous reports regarding clinical and imaging features. Low serum uric acid and homocysteine levels are important and accessible diagnostic clues."

Clinical • CNS Disorders • Endocrine Disorders • Epilepsy • Genetic Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Ventriculomegaly • MOCS1 • MOCS2

Clinical and biochemical footprints of inherited cofactor disorders. (PubMed, Mol Genet Metab) - "We summarize pathomechanisms and current treatment options, emphasizing time-critical, treatable conditions (e.g., cyclic pyranopterin monophosphate (cPMP; fosdenopterin) replacement in MoCo-A; neurotransmitter and vitamin replacement strategies)...While newborn screening is well established for disorders of BH4 metabolism, screening for several other disorders, such as PDE-ALDH7A1 deficiency, is still in the pilot phase and available only in a few specialized centers. In contrast, genomic screening, with all its benefits and pitfalls, is emerging as a complement to classic newborn screening."

Journal • Review • CNS Disorders • Epilepsy • Metabolic Disorders • Movement Disorders • ALDH7A1

Treatable Neonatal Molybdenum Cofactor Deficiency: Rapid Demise Despite Rapid Biochemical Diagnosis. (PubMed, JIMD Rep) - "Although the biochemical genetics laboratory's protocol for analyzing and reporting S-sulfocysteine levels within 48 h enabled a rapid preliminary diagnosis, the patient's condition deteriorated too quickly to initiate disease-altering treatment, progressing more rapidly than described in the literature. We discuss potential hypotheses for his rapid decline and the broader implications for the field of biochemical genetics."

Journal • CNS Disorders • Epilepsy • Genetic Disorders • Infectious Disease • Metabolic Disorders • Respiratory Diseases • MOCS1

Increased survival and improved clinical outcomes in patients with MoCD Type A treated with cyclic pyranopterin monophosphate (cPMP)/fosdenopterin (SSIEM 2023) - "This updated analysis demonstrated that pts with MoCD Type A who received cPMP were more likely to survive, feed orally, achieve growth and development milestones, and be ambulatory, and that cPMP was generally well-tolerated."

Clinical • Clinical data • CNS Disorders • Gastrointestinal Disorder • Genetic Disorders • Infectious Disease • Metabolic Disorders • Pneumonia • Rare Diseases • Respiratory Diseases • Respiratory Syncytial Virus Infections

Early Neonatal Fosdenopterin Treatment for Molybdenum Cofactor Deficiency Type A: New Insights into Its Natural History and Potential Role for Fetal Therapy. (PubMed, J Clin Med) - " This case highlights that brain injury in MoCD-A may commence in utero during the second trimester. Early delivery combined with immediate neonatal fosdenopterin treatment controlled seizures and halted progression, but residual injury suggests that prenatal interventions are necessary to optimize outcomes."

Journal • Cerebral Palsy • CNS Disorders • Epilepsy • Genetic Disorders • Metabolic Disorders • Vascular Neurology

Real-World Evidence in New Drug and Biologics License Application Approvals During Fiscal Years 2020-2022. (PubMed, Clin Pharmacol Ther) - "The first report covered fiscal year (FY) 2023 and described two approvals based, at least in part, on RWE: tocilizumab (trade name Actemra) and lacosamide (trade name Vimpat)...RWE contributed to substantial evidence of effectiveness for the approval of applications for fosdenopterin (trade name Nulibry) and tacrolimus (trade name Prograf) in FY 2021 and abatacept (trade name Orencia), vosoritide (trade name Voxzogo), and alpelisib (trade name Vijoice) in FY 2022...Four studies leveraged registry data, and two leveraged medical record data. In parallel with annual RWE public reporting under PDUFA VII, this report can inform interested parties regarding how RWD are used to generate RWE that can support regulatory decision making for medical products."

BLA • HEOR • Journal • Real-world evidence

Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate. (PubMed, J Inherit Metab Dis) - "Fosdenopterin/rcPMP was generally well-tolerated. Improved outcomes in patients treated early support the importance of identifying MoCD in neonates and initiating treatment as soon as possible."

Biomarker • Journal • Retrospective data • CNS Disorders • Genetic Disorders • Metabolic Disorders

Early postnatal hepatocyte transplantation in a child with molybdenum cofactor deficiency type B. (PubMed, Mol Genet Metab) - "Whilst there is now an emerging therapy for MoCD Type A (cPMP/fosdenopterin), this treatment is not effective for MoCD Type B and there is no treatment for isolated sulfite oxidase deficiency (ISOD)...Whilst there was evidence of biochemical stabilization with reduction in concentrations of sulfite and S-sulfocysteine and a moderate increase in urate levels compared to the sibling, the treatment was not able to prevent acute brain injury from sulfite toxicity which was evident in neuroimaging at 35 h of age. This correlated clinically with ongoing seizures as well as minimal developmental progress."

Journal • CNS Disorders • Epilepsy • Genetic Disorders • Hepatology • Metabolic Disorders • Transplantation • Vascular Neurology

cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant. (PubMed, Mol Genet Metab) - "This case provides further evidence that cPMP substitution does significantly alter the disease course when applied early enough. Postnatal treatment in this case was not sufficient to enable an entirely normal cognitive development, despite sustained complete normalization of the biochemical abnormalities."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • Hypoglycemia • Metabolic Disorders • Vascular Neurology • MOCS1

CONSENSUS GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF ISOLATED SULFITE OXIDASE DEFICIENCY AND MOLYBDENUM COFACTOR DEFICIENCIES (SSIEM 2024) - "One of the four disorders, molybdenum cofactor deficiency type A (MoCD-A) has recently become amenable to causal treatment with synthetic cPMP (fosdenopterin)... The guidelines reflect expert consensus opinion after evaluation of the evidence from a systematic literature search."

Genetic Disorders • Metabolic Disorders

Pharmacodynamic profiling in three patients with molybdenum cofactor deficiency type A reveals prolonged biological effects after withdrawal of cyclic pyranopterin monophosphate. (PubMed, Mol Genet Metab) - "We found that the clinical and metabolic effects were sustained for longer than expected, over 7 days at least. Our data implicate a biological half-life of the molybdenum cofactor dependent enzyme activities of approximately 3 days and suggest the possibility that less frequent than once daily dosing intervals could be a safe alternative to current practice."

Journal • PK/PD data • Genetic Disorders • Metabolic Disorders

Consensus guidelines for the diagnosis and management of isolated sulfite oxidase deficiency and molybdenum cofactor deficiencies. (PubMed, J Inherit Metab Dis) - "One of the four disorders, molybdenum cofactor deficiency type A (MoCD-A) has recently become amenable to causal treatment with synthetic cPMP (fosdenopterin)...The guidelines were developed by experts in diagnosis and treatment of sulfite intoxication disorders. It reflects expert consensus opinion and evidence from a systematic literature search."

Journal • Review • Cerebral Palsy • CNS Disorders • Genetic Disorders • Metabolic Disorders

Examine the Use of Real-World Evidence To Support FDA Decision-Making for New Drug Applications and Biologics License Applications From 2021 to 2022 (ISPOR 2024) - "The application of fosdenopterin utilized RWE as primary evidence for effectiveness, while others used RWE as supportive evidence... In recent FDA’s regulatory decisions for NMEs, RWE have been incorporated into their submissions for diseases with high unmet needs. To support effectiveness, RWE has been applied as an external control arm to compare with single-arm trials or as a description of the disease’s natural history. However, it is crucial to address biases during the analysis to minimize potential harmful effects."

Clinical • HEOR • Real-world • Real-world evidence • Dermatology • Oncology

The Genetic Prevalence of Molybdenum Cofactor Deficiency as a Result of MOCS1 and MOCS2: A Genetics and Biostatistics Perspective (ACMG 2024) - "The first drug treatment, fosdenopterin, was approved in 2021 for treating MoCD type A by the FDA... This investigation found 8 MOCS1 carriers and no MOCS2 carriers in the healthy unrelated individuals of the 1KG population. The literature reports an estimated global incidence of MoCD is 1 in 100,000 to 1 in 200,000. Additionally, the literature specifies that 50-60% of patients with MoCD are affected by MOCS1 pathogenic variants while 33% are affected by MOCS2 variants."

CNS Disorders • Epilepsy • Genetic Disorders • Metabolic Disorders • MOCS1 • MOCS2

Molybdenum Cofactor Deficiency in Humans. (PubMed, Molecules) - "Substitution therapy with cPMP is highly effective in reducing sulfite toxicity and restoring biochemical homeostasis, while the clinical outcome critically depends on the degree of brain injury prior to the start of treatment. In the absence of a specific treatment for MoCD type B/C and SOX deficiency, we summarize recent progress in our understanding of the underlying metabolic changes in cysteine homeostasis and propose novel therapeutic interventions to circumvent those pathological changes."

Journal • Review • CNS Disorders • Dystonia • Epilepsy • Genetic Disorders • Metabolic Disorders • Movement Disorders • Vascular Neurology

Study of ORGN001 (Formerly ALXN1101) in Neonates, Infants and Children With Molybdenum Cofactor Deficiency (MOCD) Type A (clinicaltrials.gov) - P2/3 | N=5 | Completed | Sponsor: Origin Biosciences | Enrolling by invitation ➔ Completed

Trial completion • Genetic Disorders • Metabolic Disorders

Safety & Efficacy Study of ORGN001 (Formerly ALXN1101) in Pediatric Patients With MoCD Type A Currently Treated With rcPMP (clinicaltrials.gov) - P2 | N=7 | Completed | Sponsor: Origin Biosciences | Active, not recruiting ➔ Completed | Trial primary completion date: Dec 2022 ➔ Jul 2022

Trial completion • Trial primary completion date • Genetic Disorders • Metabolic Disorders • Pediatrics

"$BBIO BridgeBio Pharma and Sentynl Therapeutics Receive Marketing Authorization in the EU for NULIBRY® (fosdenopterin) for the Treatment of MoCD Type A https://t.co/8SxENlJF7p" (,@stock_titan)

Genetic Disorders • Metabolic Disorders

Study of ORGN001 (Formerly ALXN1101) in Neonates, Infants and Children With Molybdenum Cofactor Deficiency (MOCD) Type A (clinicaltrials.gov) - P2/3 | N=5 | Enrolling by invitation | Sponsor: Origin Biosciences | Recruiting ➔ Enrolling by invitation

Enrollment status • Genetic Disorders • Metabolic Disorders

Study of ORGN001 (Formerly ALXN1101) in Neonates, Infants and Children With Molybdenum Cofactor Deficiency (MOCD) Type A (clinicaltrials.gov) - P2/3 | N=5 | Recruiting | Sponsor: Origin Biosciences | Trial primary completion date: Dec 2021 ➔ Jul 2022

Trial primary completion date • Genetic Disorders • Metabolic Disorders

Safety & Efficacy Study of ORGN001 (Formerly ALXN1101) in Pediatric Patients With MoCD Type A Currently Treated With rcPMP (clinicaltrials.gov) - P2; N=7; Active, not recruiting; Sponsor: Origin Biosciences; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Genetic Disorders • Metabolic Disorders • Pediatrics

Nulibry (fosdenopterin) Approved to Reduce the Risk of Mortality in Patients with Molybdenum Cofactor Deficiency Type A: FDA Approval Summary. (PubMed, J Inherit Metab Dis) - No abstract available

Clinical • FDA event • Journal • Genetic Disorders • Metabolic Disorders

Study of ORGN001 (Formerly ALXN1101) in Neonates, Infants and Children With Molybdenum Cofactor Deficiency (MOCD) Type A (clinicaltrials.gov) - P2/3; N=5; Recruiting; Sponsor: Origin Biosciences; Trial completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial completion date • Genetic Disorders • Metabolic Disorders

Fosdenopterin. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal

Fosdenopterin: First Approval. (PubMed, Drugs) - "Fosdenopterin (Nulibry) is a synthetic cyclic pyranopterin monophosphate that is being developed by Origin Biosciences (a subsidiary of BridgeBio Pharma) for the treatment of molybdenum cofactor deficiency (MoCD) type A. Fosdenopterin was recently approved by the US FDA for use in reducing the risk of mortality in paediatric and adult patients with MoCD type A. This article summarizes the milestones in the development of fosdenopterin leading to this first approval."

Journal • Review • Pediatrics