Protalix, Chiesi Resubmit BLA to Treat Fabry Disease

Protalix BioTherapeutics and Chiesi Global Rare Diseases have resubmitted the biologics license application (BLA) for PRX-102 (pegunigalsidase alfa) to treat adult patients with Fabry disease. Fabry disease is a life-threatening, rare genetic disorder that can cause pain and impaired peripheral sensation and can lead to organ failure, particularly of the kidneys. It is caused by a deficiency of the lysosomal α–Galactosidase–A enzyme, which leads to abnormal deposits of a fatty substance called globotriaosylceramide (Gb3) in blood vessel walls. Fabry disease occurs in one person per 40,000 to 60,000.

“We believe PRX-102, if approved, has the potential to significantly impact patients living with this rare, life-threatening genetic disease. As we approach potential approval and commercialization of PRX-102, we affirm our dedication to our mission of bringing new medicines to patients with serious diseases,” Dror Bashan, Protalix's president and chief executive officer, said in a press release.

PRX–102 is an enzyme replacement therapy. It is a long-acting and chemically modified stabilized version of the recombinant α–Galactosidase–A enzyme.

The companies had received a complete response letter from the FDA in April 2021. At the time, the agency indicated that travel restrictions limited the ability to complete inspections of Protalix’s manufacturing facility in Israel.

The FDA also indicated that Sanofi’s Fabrazyme (agalsidase beta) was recently converted to full approval as an enzyme replacement therapy for Fabry disease, and any potential resubmission seeking accelerated approval of PRX‑102 must address this.

The data in the resubmission were compiled from studies that involved more than 140 Fabry disease patients with up to five years of follow up. These include all three completed studies in the PRX-102 phase 3 clinical program: the BALANCE study, the BRIDGE study and the BRIGHT study, as well as the phase 1/2 clinical trial of PRX-102. The phase 1/2 data includes data compiled from the related extension study. The BLA resubmission also includes safety data compiled from the ongoing phase 3 extension studies of PRX–102.

The BRIGHT study, released in March 2022, met key objectives for safety, efficacy and pharmacokinetics. Treatment with PRX-102 provided coverage for the entire four‑week period between infusions. No patients developed treatment-induced anti-drug antibodies to PRX-102.

The study enrolled 30 adult patients with Fabry disease ranging from 19 to 58 years who previously received an approved enzyme replacement therapy for at least three years on a stable dose administered every two weeks.

The BALANCE study, released in April 2022, met the primary endpoint on kidney function in active control, non-inferiority study vs. Fabrazyme. Topline results demonstrated a favorable tolerability and immunogenicity profile for PRX-102. The study enrolled 78 patients who were previously treated with agalsidase beta for at least one year.