Molybdenum Cofactor Deficiency

The therapy has demonstrated benefits in five main studies enrolling 52 subjects with MoCD type A. Credit: Shironagasukujira / Shutterstock.com. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved TMC Pharma’s fosdenopterin (Nulibry) for the treatment of molybdenum cofactor deficiency (MoCD) type A. This rare genetic disorder is characterised by the body’s inability to produce cyclic pyranopterin monophosphate, leading to toxic sulphite accumulation that damages the brain. Symptoms apparent from birth include seizures, poor muscle tone and small head size. The authorisation, which is based on a decision by the European Commission (EC) and advice from the Committee for Medicinal Products for Human Use, follows the EC decision reliance procedure. Fosdenopterin is offered as a 9.5mg powder in solution for injection, administered intravenously through a catheter. It has demonstrated benefits in five main studies enrolling 52 subjects with MoCD type A. These trials assessed the impact of fosdenopterin on survival following a treatment period of one year. See Also: Oryzon wins FDA approval to begin SCLC treatment trial J&J and Legend’s Carvykti scores early line approval for MM by FDA 93% of subjects treated with fosdenopterin survived beyond one year, in contrast to a 75% survival rate in those who did not receive the treatment. Initiating fosdenopterin treatment early, before the onset of significant brain damage, has been linked to preserved oral feeding abilities and enhanced growth, motor and cognitive development. Pain, redness, discharge and inflammation were the most common side effects of the medicine linked to the catheter. MHRA healthcare quality and access interim executive director Julian Beach stated: “Keeping patients safe and enabling their access to high quality, safe and effective medical products are key priorities for us. “We’re assured that the appropriate regulatory standards for the approval of this medicine have been met. “As with all products, we will keep its safety under close review.”

Risk of death was 5.1 times higher in untreated patients versus patients treated with NULIBRY Treatment also led to improvements in urinary biomarker levels and development outcomes NULIBRY is the first therapy to reduce the risk of mortality in patients with known or presumed MoCD Type A SOLANA BEACH, Calif., Sept. 7, 2023 /PRNewswire/ -- Sentynl Therapeutics, Inc. (Sentynl), a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases, announced that data evaluating NULIBRY® (fosdenopterin) for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A were presented at the 2023 Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Meeting on Aug. 30 in Jerusalem. NULIBRY is indicated to reduce the risk of mortality in patients with MoCD Type A, an ultra-rare, autosomal recessive, inborn error of metabolism causing sulfite-induced neurodegeneration and early death. "Clinicians must consider MoCD in infants with encephalopathy or intractable seizures," said Dr. Guenter Schwarz, Professor for Biochemistry at the Department of Chemistry & Center for Molecular Medicine, Cologne University, Germany. "Early treatment with fosdenopterin (NULIBRY) improves survival and neurodevelopmental outcomes, reducing burden on patients and caregivers." In comparison of three non-randomized retrospective and prospective open-label studies versus a retrospective and prospective natural history study, the authors reported the following survival and clinical outcomes of patients treated with recombinant cPMP/NULIBRY: Risk of death was 5.1 times higher in untreated MoCD Type A patients compared to those treated with rcPMP/NULIBRY (Cox proportional hazards [95% CI]=5.1 [1.32, 19.36], P=0.0144). Treatment with rcPMP/NULIBRY led to a normalization of MoCD Type A-associated urinary biomarker levels. Treated patients were more likely than untreated patients to feed orally and meet growth and developmental milestones. "These results were pooled from a series of carefully designed studies and corroborate previous anecdotal findings. Early treatment of children with typical neonatal disease manifestation has a dramatic effect on their survival and overall development," said Dr. Bernd C. Schwahn, Consultant in Paediatric Metabolic Medicine, Manchester Centre for Genomic Medicine, St. Mary's Hospital, in Manchester, United Kingdom. "Increased disease awareness and the use of new technologies, including improved biochemical testing and rapid whole genome sequencing, will help to shorten the diagnostic gap and allow timely access to effective treatment for a higher proportion of affected children." Based on these data, NULIBRY was approved by the U.S. Food and Drug Administration, the European Medicines Agency and the Israeli Ministry of Health. To further evaluate the safety and efficacy of NULIBRY, a post-approval non-interventional study is being initiated in Europe. "Given Sentynl's focus on meaningful treatments for serious rare diseases, we are grateful to the authors for presenting these data and increasing awareness of MoCD Type A in the medical community," said Matt Heck, CEO of Sentynl. "We thank the patients, their families and caregivers, and all investigators involved in this study. We remain focused on continued evaluation of NULIBRY to reduce the risk of mortality and progression of this devastating disease." Treatment with NULIBRY/rcPMP was generally well-tolerated in patients with MoCD Type A. Most patients experienced a treatment-emergent adverse event (TEAE), the majority of which were catheter-related or infections and were mild to moderate in severity. In the retrospective study, two serious TEAEs of death occurred, one from RSV pneumonia (unrelated to treatment), and one from necrotizing enterocolitis (possibly related to treatment). Please click here for full Prescribing Information of NULIBRY. 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 estimated prevalence of MoCD Type A in the European Union is 0.005 per 10,000. 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. About NULIBRY® (fosdenopterin) for Injection NULIBRY® (fosdenopterin) for Injection is a substrate replacement therapy that provides an exogenous 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 is approved by the U.S. Food and Drug Administration, the European Medicines Agency and the Israeli Ministry of Health for the treatment of patients with known or presumed MoCD Type A (discontinued if MoCD Type A is not confirmed), and it is the first and only FDA-approved therapy indicated to reduce the risk of mortality in patients with MoCD Type A. Clinical trials have demonstrated that patients treated with NULIBRY or rcPMP had an improvement in overall survival compared to the untreated, genotype-matched, historical control group. References 1 Mechler K et al. Genet Med. 2015;17(12):965-970. 2 Schwarz G. Cur Op in Che Bio. 2016;31:179-187. About Sentynl Therapeutics Sentynl Therapeutics 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 committed to the highest ethical standards and compliance with all applicable laws, regulations and industry guidelines. For more information, visit . SOURCE Sentynl Therapeutics

OXFORD, England, March 07, 2023 (GLOBE NEWSWIRE) -- MitoRx Therapeutics (MitoRx), a biotechnology company developing revolutionary therapeutics that reverse mitochondrial dysfunction to arrest the progression of degenerative diseases, announces Christine Charman as Chief Development Officer, David Richardson as Finance Director, and four appointments to its Scientific Advisory Board (SAB): Prof Chas Bountra, Prof Dame Kay Davies, Prof Laurent Servais, and Dr Bernd C Schwahn. Prof Chas Bountra OBE is now Chair of the Scientific Advisory Board. He commented on his appointment: “It’s an honour and a pleasure to come together with top international scientific and clinical experts to build the MitoRx Scientific Advisory Board. Together we are working to become a global leader in treating diseases caused by impaired mitochondrial function.” Chas is Pro-Vice Chancellor for Innovation at the University of Oxford, Professor of Translational Medicine in the Nuffield Department of Clinical Medicine, Director of the Centre for Medicines Discovery, and Professorial Fellow at Keble College, Oxford. Prior to coming back to Oxford in 2008, Chas was Vice President and Head of Biology at GlaxoSmithKline. Chas is an invited expert on several government and charitable research funding bodies, and an advisor for many academic, biotech and pharma drug discovery programmes. In 2012 he was voted one of the “top innovators in the industry”, in 2014 received the “Rita and John Cornforth Award” from the Royal Society of Chemistry, in 2017 and 2018 was voted “Master of the Bench” from the Medicine Maker Power List, and in 2018 was awarded the “Order of the British Empire” in the New Years Honours List. Also joining the board is Prof Dame Kay Davies CBE DBE FRS FMedSci, Dr Lee’s Professor of Anatomy Emeritus at the University of Oxford with an international reputation for work on Duchenne muscular dystrophy paving the way for several nucleic acid related therapies. Prof Davies is a co-founder and co-Director of the MDUK Oxford Neuromuscular Centre, and co-founded Summit Therapeutics plc to translate her work into the clinic. Prof Laurent Servais MD PhD directs the Specialised Translational Research Oxford Neuromuscular Group as Professor of Paediatric Neuromuscular Disease at the University of Oxford, and he is Professor of Child Neurology at the University of Liège. He brings a wealth of experience to the Scientific Advisory Board having led many clinical trials as principal investigator for Duchenne muscular dystrophy and spinal muscular atrophy treatments. Dr Bernd C Schwahn MD PhD FRCPCH, Consultant in Paediatric Metabolic Medicine at the Manchester University NHS Foundation Trust and Honorary Clinical Senior Lecturer in Genomic Medicine, also joins the board. Dr Schwahn’s scientific interest focuses on disorders of sulfur amino acid metabolism and has been involved as principal and chief investigator in clinical trials for the treatment of molybdenum cofactor deficiency, lysosomal storage disorders and disorders of intermediary metabolism. Chief Development Officer Christine Charman PhD comes with close to 26 years’ experience in accelerating transformational therapies as Senior Global Program Lead for Takeda’s Rare Diseases, Respiratory and Immunology and Neuroscience therapy areas. She also worked as consultant CDO at Izana Bioscience and development consultant for a range of Biotechs and NewCos and Program Lead supporting UK Vaccine and Antiviral Task Forces, with further development experience at Novartis from preclinical research leadership to Senior Global Programme Director, including the planning, clinical execution and launch of two products. David Richardson BSc ACMA AMCT brings over 30 years finance experience to his new role as Finance Director. He has held board positions at a number of venture-backed technology companies and his experience in the industry includes senior finance roles within both AstraZeneca and Evotec. Jonathan Rees PhD, CEO of MitoRx, said, “We are thrilled to welcome our new SAB members, as well as Christine Charman as Chief Development Officer and David Richardson as Finance Director, who together bring a wealth of renowned experience across financial, scientific and clinical backgrounds. The wide ranging expertise gained from our growing team and advisory board will accelerate progress of our first-in-class, first-in-target small molecules which are now being pre-clinically tested in a mammalian model of muscular dystrophy. We look forward to working with them all.” Notes to Editors Media Contact (Scius Communications) Katja StoutEmail: katja@sciuscommunications.comPhone: +44(0)7789 435990 Daniel Gooch Email: Daniel@sciuscommunications.comPhone: : +44(0)7747 875 479 Company Contact (MitoRx) Jonathan Rees, CEOEmail: jon.rees@mitorxtherapeutics.comPhone: +44(0)7826 556622 About MitoRx At MitoRx our mission is to become the leading global developer of medicines arresting the progression of degenerative diseases driven by mitochondrial dysfunction. We are a preclinical research stage biotechnology company developing our first-in-class, orally delivered, mitochondrial protective therapeutics targeting rare neuromuscular disorders, rare metabolic diseases, and neurodegenerative diseases. Located in Harwell Oxford, we have raised seed financing from a broad range of investors including the UK Innovation & Science Seed Fund, The Fink Family Office, Science Angel Syndicate, Oxford Technology Management, Wren Capital, Longevitytech.fund, as well as angel investors. For more information visit our website at www.mitorxtherapeutics.com and follow us on LinkedIn.