Krabbe Disease Gene Therapy Receives Second Orphan Drug Designation


Forge Biologics and Solid Biosciences have also partnered to help develop a gene therapy for Duchenne muscular dystrophy.

The EMA has granted orphan drug designation to Forge Biologics’ FBX-101, an investigational adeno-associated virus (AAV)-directed gene therapy for patients with Krabbe disease.1

Forge Biologics announced the designation along with other regulatory updates in a statement. They also shared that they received positive feedback from the FDA on their AAV production processes, proprietary plasmids, including their pEMBR helper plasmid, and Ignition HEK293 suspension cell line. 

“FBX-101 is the culmination of over 20 years of scientific research to understand the challenges faced by patients with progressive disease after hematopoietic stem cell transplantation, the current standard of care,” said Maria Escolar, MD, chief medical officer, Forge Biologics, in the statement.1 “We are currently recruiting patients for our RESKUE clinical trial to administer FBX-101 and we are pleased by the EMA’s designation so that patients in Europe may also have access to this potentially transformative therapeutic approach.”

FBX-101 is designed to deliver a corrected version of the mutated GALC gene that causes Krabbe disease. The FDA previously granted orphan drug and rare pediatric disease designations to FBX-101 earlier in 2021.

READ MORE: SGT-001 Improves Pulmonary Function in Duchenne Muscular Dystrophy

FBX-101 is being evaluated in the phase 1/2 nonblinded, non-randomized, dose escalation, RESKUE trial (NCT04693598) for the potential treatment of Krabbe disease. Participants will receive standard of care hematopoietic cell transplantation (HSCT) followed by a single infusion of FBX-101 and will be compared to natural history as a control. The study is currently recruiting and aims to enroll 6 participants with an estimated study completion date of April 2023.

RESKUE will assess both a high and low dose of FBX-101. Primary outcomes will measure safety in terms of organ-specific adverse event (AE) severity and HSCT engraftment.Secondary outcomes will assess efficacy, specifically achieving independent sitting and gross motor function as measured by Peabody Developmental Motor Scales. Other exploratory endpoints will record biomarkers and other responses.

“We are excited that the tools we have developed at Forge will help accelerate and scale cGMP production of AAV gene therapies for patients. We are thankful to have a positive dialogue with the EMA and for gaining alignment with the FDA on the suitability of our key production materials for our own and our clients’ use,” Christopher Shilling, vice president, regulatory affairs and quality, Forge Biologics, added to the statement.1 “These new technologies can help mitigate current safety concerns surrounding critical raw materials used in AAV scale-up and production processes for programs moving from research to clinical stage.”

Forge Biologics also recently partnered with Solid Biosciences to facilitate the development and manufacturing of SGT-003, Solid’s investigational gene therapy for the potential treatment of Duchenne muscular dystrophy.2 Forge will use their validated manufacturing processes to advance the product’s clinical development.

“We are excited to partner with Forge, a company who shares our high standards for product purity, potency and reproducibility, to further our ability to bring meaningful therapies to patients with Duchenne,” said Joel Schneider, PhD, chief operating officer, Solid Biosciences, in a statement.2 “As we continue to develop our pipeline, it is important that we have partners who will enhance our expertise. Uniting Forge’s integrated platforms and cGMP gene therapy manufacturing capabilities with our in-depth knowledge in high dose gene therapy development and manufacturing will introduce an additional method to produce AAV gene therapy at Solid, and help to accelerate human proof of concept for SGT-003.”

1. Forge Biologics announces regulatory updates from FDA and EMA, accelerating manufacturing and clinical trial momentum. News release. Forge Biologics. September 20, 2021.
2. Solid Biosciences and Forge Biologics announce viral vector contract development and cGMP manufacturing partnership. News release. Forge Biologics. October 4, 2021.
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