Pipeline & Science
Developing gene therapies for life
Pipeline & Science
Forge is developing innovative gene therapies that aim to help patients suffering from devastating rare diseases.
Krabbe Disease & FBX-101
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 insulating the nerves in the brain and peripheral nervous system, causing rapid demyelination. Krabbe disease initially manifests as irritability, developmental delay, and progressive muscle weakness; symptoms rapidly advance to difficulty swallowing, breathing, 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 2 years of age; Late Infantile patients (12-36 months of age at onset) usually die by the age of six1. 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 onset2. However, HSCT does not correct the peripheral neuropathy that is progressive as the patient grows, leading to loss of gross motor skills and eventually death3. Early diagnosis is key for treating Krabbe patients before significant neurological damage has occurred. Currently, 10 states in the U.S. are conducting newborn screening for Krabbe disease. Infants who screen positive due to insufficient GALC activity undergo psychosine and mutation analysis to confirm the diagnosis and determine which infants need immediate treatment because they are at high risk to progress.
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 infusion. 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 approach has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies and extend the duration of gene transfer. 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.
About the RESKUE Trial
RESKUE is a Phase 1/2 clinical trial to investigate the safety and efficacy of FBX-101 in patients with infantile Krabbe disease. It is a nonblinded, non-randomized dose escalation study in which subjects receive a single intravenous infusion of FBX-101 within 21 to 60 days of HSCT, the current standard of care. Data from extensive natural history subjects will be used to compare as the control group. More information on the RESKUE trial can be found online at https://www.clinicaltrials.gov/ct2/show/NCT04693598
About the REKLAIM Trial
REKLAIM is a Phase 1b, nonblinded, non-randomized dose escalation clinical trial currently enrolling children with asymptomatic infantile and symptomatic late infantile Krabbe disease to investigate the safety and efficacy of a single intravenous infusion of FBX-101 administered more than 90 days after HSCT, the current standard of care, when the patient is partially or fully immuno-competent. Data from extensive natural history subjects will be used to compare as the control group. More information on the REKLAIM trial can be found online at https://www.clinicaltrials.gov/ct2/show/NCT05739643.
Expanded Access Policy
We recognize the value of the Expanded Access program and are dedicated to patient-focused drug development. At this time, we are unable to commit to expanded access of FBX-101 for the general Krabbe patient population while safety assessments are ongoing. All requests for Expanded Access will be referred to study investigators to determine a patient’s eligibility for a clinical study. In very exceptional circumstances, Expanded Access requests may be considered on a case-by-case basis. These will only be considered in lieu of a patient who does not qualify for an ongoing clinical study and based on the potential benefit/risk profile of the experimental medicine for that specific individual patient based on existing safety and efficacy data.
For more information about our clinical trials or Expanded Access, patients, pediatricians, caregivers, and foundations are encouraged to reach out to email@example.com. Physicians may also email to refer a patient to our clinical trials. A team member from Forge will respond within five business days.
A Note from the Forge Team
If someone you love was recently diagnosed with Krabbe disease, you are the reason we are aiming everything we have – our time, talents, and resources – towards safely, effectively, and expediently bringing healing to Krabbe patients. We are more than just a company; we are a collection of real people that care deeply about connecting with, listening to, and understanding the patients and families we serve. If you or someone close to you has been affected by Krabbe and you’d like to connect with us, simply reach out at firstname.lastname@example.org. We’re here to listen, learn, and help however we can.
1. Bascou, N., A. DeRenzo, M. D. Poe, and M. L. Escolar. 2018. 'A prospective natural history study of Krabbe disease in a patient cohort with onset between 6 months and 3 years of life', Orphanet J Rare Dis, 13: 126.
2. Escolar, M. L., M. D. Poe, J. M. Provenzale, K. C. Richards, J. Allison, S. Wood, D. A. Wenger, D. Pietryga, D. Wall, M. Champagne, R. Morse, W. Krivit, and J. Kurtzberg. 2005. 'Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease', N Engl J Med, 352: 2069-81.
3. Wright, M. D., M. D. Poe, A. DeRenzo, S. Haldal, and M. L. Escolar. 2017. 'Developmental outcomes of cord blood transplantation for Krabbe disease: A 15-year study', Neurology, 89: 1365-72.
4. Rafi MA, Rao HZ, Luzi P, et al. Long-term improvements in lifespan and pathology in CNS and PNS after BMT plus one intravenous injection of AAVrh10-GALC in twitcher mice. Mol Ther 2015; 23:1681–1690.
About Gene Therapy
Gene therapies are transformative medicines that hold promise for treating diverse, genetically-driven diseases. Genetic diseases are caused by alterations in genes that result in the defective function or complete absence of important proteins in cells. Gene therapies can help to correct these defects by replacing or modifying the mutated gene(s). The essential components of a gene therapy are: