Developing gene therapies for life
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 leukodystrophy affecting about 1 in 100,000 people in the U.S. and is inherited in an autosomal recessive manner. Krabbe disease is caused by loss-of-function mutations in the galactosylceramidase (GALC) gene, a lysosomal enzyme responsible for the breakdown of certain types of lipids such as psychosine. Without functional GALC, psychosine accumulates to toxic levels in cells. The psychosine toxicity is most severe in the protective cells surrounding the nerves in the brain and throughout the body (peripheral nervous system), eventually leading to the death of these cells. The progressive neuronal cell death manifest over the course of the disease: initially presenting as mental and physical delays in development, muscle weakness and irritability and advancing rapidly to vision and hearing loss and difficulty swallowing and breathing. Early onset, “Early Infantile”, Krabbe cases usually results in death by age 2, while later onset “Late Infantile” cases have a more variable course of progressive decline1. There is currently no cure for either form of Krabbe disease.
The current standard of care for early infantile Krabbe disease, hematopoietic stem cell transplant (HSCT), was pioneered by Dr. Maria Escolar2. After HSCT, symptoms of disease have been shown to stabilize by neurological assessment, and survival has improved through correction of the GALC deficiency in the brain. However, HSCT does not effectively correct the GALC deficiency in the peripheral nervous system and as pediatric patients grow, they will progressively lose motor and sensory skills eventually resulting in death3.
The RESKUE Trial - a Phase 1/2 Clinical Trial for Patients with Krabbe Disease:Screening will begin in early 2021 for the Phase 1/2 RESKUE trial. FBX-101 utilizes adeno-associated viral (AAV) gene therapy after hematopoietic stem cell transplant (HSCT) to deliver a functioning copy of the GALC gene, which encodes an enzyme needed to prevent the buildup of psychosine in myelinated cells of both the central and peripheral nervous system. FBX-101 has been shown to functionally correct the central and peripheral myelination deficits, significantly improve the behavioral impairments associated with Krabbe disease in animal models, and drastically improve the lifespan of treated animal models of the disease. The use of transplant and intravenous AAV gene therapy infusion has the potential to overcome some of the immunological safety challenges of traditional AAV gene therapies.
FBX-101, for the treatment of patients with Krabbe disease, is currently in the early phase of clinical development, and the focus of our initial “RESKUE” Phase 1/2 clinical trial will be an evaluation for safety of FBX-101. These clinical trials are designed and implemented to gain an understanding of the safety and efficacy of FBX-101. Participation in these clinical trials, accepted by the U.S. Food and Drug Administration (FDA), or other regulatory authorities, is the best way for patients to access investigational therapies for their diseases.
More information on the ongoing “RESKUE” clinical trial can be found online at https://www.clinicaltrials.gov/ct2/show/NCT04693598.
A Note From Our Forge Family
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.
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.
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: