Krabbe disease(Gain Therapeutics)

Data from Krabbe patients treated with hematopoietic stem cell transplantation (HSCT) and FBX-101 gene therapy in clinical trials continue to demonstrate safety and efficacy post-FBX-101 systemic administration Five patients have received FBX-101, all of whom were identified by newborn screening CEO Timothy J. Miller, Ph.D., is slated to comment during the public meeting of the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) to reinforce the importance of the addition of Krabbe Newborn Screening to the national Recommended Newborn Screening Panel (RUSP) on Tuesday, January 30, 2024 Dr. Maria Escolar, Chief Medical Officer, will present updated FBX-101 clinical data as a late-breaking oral presentation on Friday, February 9, 2024, during the 10:30 a.m. ET session at the WORLD Symposium in San Diego, California COLUMBUS, Ohio--(BUSINESS WIRE)-- Forge Biologics (Forge), a member of Ajinomoto Bio-Pharma Services and a leading manufacturer of genetic medicines, announced a clinical update today on five patients with Krabbe disease that have received FBX-101, an AAV gene therapy, after hematopoietic stem cell transplantation (HSCT). Timothy J. Miller, Ph.D., CEO and President of Forge Biologics, will provide comments during the open period at the public meeting of the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) on Tuesday, January 30, 2024, in support of adding Krabbe disease to the Recommended Uniform Screening Panel (RUSP). Krabbe disease is caused by mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine, associated with myelination of the nervous system. Without functional GALC, psychosine accumulates to toxic levels in cells, damaging cells that myelinate and insulate the nerves in the brain and peripheral nervous system, causing rapid demyelination and eventual death. Infantile Krabbe patients, often not diagnosed until after significant disease manifestations have occurred, typically die by the age of two if not treated by HSCT before symptoms are observed. Previously published data have demonstrated that patients with Krabbe treated with HSCT demonstrate increased lifespan and stabilization of neurodegenerative disease in the central nervous system. FBX-101, an investigational adeno-associated viral (AAV) gene therapy, has been designed to address the peripheral nerve disease not corrected by HSCT. Data recently presented at the European Society for Gene and Cell Therapy (ESGCT) demonstrated that FBX-101 provided to Krabbe patients identified through newborn screening who also received HSCT demonstrated increased GALC expression, reduced psychosine levels, normalized motor function, and corrected brain white matter growth. “Inclusion of Krabbe disease on the RUSP would extend Krabbe Newborn Screening to eight additional states, based on RUSP alignment legislation, ensuring that nearly 70% of all newborns in the United States are screened for this devastasting disease,” said Dr. Miller. “That would mean the potential of identifying dozens of babies every year, based on published incidence, who could receive the opportunity of life-saving treatments such as transplant and newly developing treatments like gene therapy.” The responsibility of the committee members of the ACHDNC is to provide the Secretary of Health and Human Services with recommendations, advice, and information to enhance, expand, or improve the ability of the Secretary to reduce mortality and morbidity from heritable disorders—such as Krabbe disease—in newborns and children. In early 2023, Krabbe disease came up for the second time (previously in 2010) to the ACHDNC for a vote to be added to the RUSP—a vote which ended in a tie of seven members voting approve, and seven members voting not to approve, something that had never happened before and has been a focus of multiple advocacy group efforts requesting a re-vote. As a result, after a year of patient and foundation advocacy, Krabbe disease is again being voted on for potential inclusion on the RUSP. “For infantile Krabbe patients, the alternative of not being able to receive a treatment such as a transplant is 100% chance of death,” said Lesa Brackbill, Director of Advocacy at Leukodystrophy Newborn Screening Action Network (LDNBS), whose daughter Victoria died from Krabbe disease in 2016. “The risk-to-benefit approach of identifying patients as early as possible in their genetic disease to help provide their children any relief, justifies the addition of Krabbe to the RUSP. Newborn screening for Krabbe will help enhance the efforts of all parents, industry partners, and treatment providers’ ceaseless search for cures.” Additionally, Maria Escolar, M.D., Chief Medical Officer, will present updated FBX-101 clinical data during the 20th Annual WORLD Symposium in San Diego, California, on February 9, 2024 at 10:30 a.m. ET. Dr. Escolar’s late-breaking oral presentation is titled, “REKLAIM, the novel phase 1b clinical trial of FBX-101 (AAVrh10.galc) intravenously administered after UCBT for the treatment of infantile Krabbe disease.” The session will also be available on demand for registered attendees February 14 to March 14, 2024. For more details on the conference, please visit: . “We continue to be encouraged by the safety and efficacy observed in FBX-101 treated patients,” stated Dr. Escolar. “The window of treatment for patients with Krabbe disease is very narrow and newborn screening is a critical step for these babies to benefit from any treatment, but unfortunately newborn screening for this devastating and quickly progressing disease is still only available in a handful of states. Dr. Miller’s comments to the ACHDNC will reflect the urgency physicians have been trying to convey for this patient community.” About Krabbe Disease Krabbe disease is a rare neurodegenerative disease affecting about 1-2.5 in 100,000 people in the U.S. Krabbe disease is caused by autosomal recessive mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine, associated with myelination of the nervous system. Without functional GALC, psychosine accumulates to toxic levels in cells, specifically in cells that make myelin insulating the nerves in the brain and peripheral nervous system, resulting in rapid demyelination. Krabbe disease initially manifests in young patients as irritability, feeding difficulties, increased muscle tone and developmental delay. Symptoms rapidly advance to difficulty breathing, and regression of neurodevelopment followed by seizures, vision and hearing loss. Infantile Krabbe disease (0-12 months of age at onset) usually leads to death in untreated patients by two years of age. Late Infantile patients (12-36 months of age at onset) usually die by the age of six. The current standard of care, hematopoietic stem cell transplantation (HSCT), has been shown to stabilize cognitive decline and significantly improve long-term neurological outcomes when performed prior to symptom onset. However, HSCT does not correct the peripheral neuropathy that is progressive as the patient grows, leading to loss of gross motor skills and eventually death. Early diagnosis is key for treating patients with Krabbe disease before symptoms are evident and significant neurological damage has occurred. Currently, 11 states in the U.S. are conducting newborn screening for Krabbe disease. Infants who screen positive due to insufficient GALC activity undergo psychosine testing and mutation analysis to confirm the diagnosis and determine which infants need immediate treatment because they are at high risk to progress. More details can be found at . About FBX-101 FBX-101 was developed to treat children with Krabbe disease. FBX-101 is an adeno-associated viral serotype rh10 (AAVrh10) gene therapy that is delivered intravenously after HSCT. The vector delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system. FBX-101 has been shown to functionally correct the central and peripheral neuropathy associated with Krabbe, improve myelination and gross motor function, and significantly prolong lifespan in animal models. This is a novel approach that has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies (without transplantation). HSCT has normal GALC and provides an immune system that does not recognize GALC as an antigen. The FDA has granted FBX-101 Fast Track Designation, Orphan Drug Designation, Rare Pediatric Disease Designation, and the EMA has granted FBX-101 Orphan Drug Designation and Priority Medicines (PRIME) designation. FBX-101 investigation use is currently being evaluated for new subjects in the REKLAIM clinical trial (NCT05739643). More information on the REKLAIM trial can be found online at . About Forge Biologics Forge Biologics, a member of Ajinomoto Biopharma Services, is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company enabling access to life-changing gene therapies by bringing them from concept to reality. Forge’s 200,000 square foot facility, the Hearth, is headquartered in Columbus, Ohio, and houses 20 custom-designed cGMP suites. Forge’s end-to-end, scalable plasmid and AAV manufacturing services include research-grade manufacturing, process and analytical development, cGMP manufacturing, fill and finish, and regulatory consulting support to help accelerate the timelines of transformative medicines for patients with genetic diseases. To learn more, visit .