RARE Daily

FDA Grants Rare Pediatric Disease Designation to Forge’s Gene Therapy for Krabbe Disease

February 16, 2021

Rare Daily Staff

The U.S. Food and Drug Administration granted Rare Pediatric Disease, Fast Track, and Orphan Drug designations to Forge Biologics’ gene therapy FBX-101 for the treatment of patients with Krabbe disease.

Krabbe disease is a rare, inherited leukodystrophy 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 myelin cells surrounding the nerves in the brain and in the peripheral nervous system, eventually leading to the death of these cells. The disease initially manifests as physical delays in development, muscle weakness and irritability, and advances rapidly to difficulty swallowing, breathing problems, cognitive, vision and hearing loss. Early onset or “infantile” Krabbe disease cases usually result in death by age two to four years, while later onset or “late infantile” cases have a more variable course of progressive decline. There is currently no approved treatment for Krabbe disease.

Forge Biologics is a hybrid gene therapy contract manufacturing and therapeutic development company. FBX-101 is the first intravenous gene therapy program for patients with Krabbe disease and marks a major step forward in building out the company’s hybrid model as a gene therapy manufacturing and development engine.

FBX-101 is an adeno-associated viral (AAV) gene therapy that is delivered after a hematopoietic stem cell transplant. FBX-101 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 and correct the behavioral impairments associated with Krabbe disease in animal models, and to drastically improve the lifespan of treated animals. This approach has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies. Forge is currently actively recruiting patients for enrollment in the RESKUE phase 1/2 clinical trial of FBX-101.

“FDA’s decision to grant these designations to our first-in-human investigational gene therapy highlights the urgency of developing a treatment for Krabbe patients,” said Timothy Miller, CEO, president and co-founder of Forge Biologics. “Krabbe is a devastating disease, and it is imperative to develop treatment options like FBX-101 that may address all manifestations of the disease.”

Fast Track designation is given when the FDA determines that a drug demonstrates the potential to address unmet medical needs for a serious or life-threatening disease or condition. This designation is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions, and may also allow for priority or rolling review of a company’s Biologics License Application (BLA).

The FDA grants Orphan Drug designation to drugs or biologics intended to treat a rare disease or condition that affects fewer than 200,000 people in the United States. Programs with Orphan Drug status receive partial tax credit for clinical trial expenditures, waived user fees and eligibility for seven years of marketing exclusivity.

The FDA grants Rare Pediatric Disease designation for serious and life-threatening diseases that primarily affect children ages 18 years or younger and fewer than 200,000 people in the United States. The designation makes each FBX-101 eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Rhythm Pharmaceutics sold its priority review voucher for $100 million in January 2021 to Alexion Pharmaceuticals.

Photo: Timothy Miller, CEO, president and co-founder of Forge Biologics

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