Protalix Asks FDA to Discuss Future of PRX-102
Protalix BioTherapeutics has requested a type A meeting with the U.S. Food and Drug Administration (FDA) to discuss a path forward for approval of PRX-102 (pegunigalsidase alfa), an investigational therapy for Fabry disease that was rejected by the regulatory agency earlier this year.
The meeting is expected to take place within 30 days of the FDA’s receipt of the request, according to a press release from Protalix dated Aug. 2.
A plant-based enzyme replacement therapy, PRX-102 aims to deliver a lab-made version of alpha-galactosidase A (the enzyme missing in Fabry disease patients) into a patient’s bloodstream. It is being developed by Protalix in collaboration with Chiesi Global Rare Diseases.
The companies’ application for approval of PRX-102 in the U.S. was accepted under priority review by the FDA last year. The agency then extended the review, before eventually rejecting the application in April.
Notably, the FDA’s rejection was not caused by concerns related to the therapy’s safety or efficacy, but because of issues with facility inspections and manufacturing processes, due in part to travel restrictions put in place because of the COVID-19 pandemic.
PRX-102’s regulatory application included a comprehensive set of preclinical, clinical, and manufacturing data to support the therapy’s approval, at a twice-monthly dose of 1 mg/kg.
This included data from the completed BRIDGE Phase 3 clinical trial (NCT03018730), which compared PRX-102 to Takeda’s Replagal (agalsidase alpha) in 22 people who had been taking Replagal for at least two years.
Replagal is an approved ERT for Fabry patients in countries that include those of the European Union, Canada, and the U.K.; it is not approved in the U.S. Results from BRIDGE showed that PRX-102 was safe, and outperformed Replagal in terms of slowing the decline in kidney function.
Safety data from the BALANCE Phase 3 study (NCT02795676), which is comparing the safety and effectiveness of PXR-102 to Fabrazyme (agalsidase beta), an approved enzyme replacement therapy marketed by Sanofi Genzyme, in 78 adults. Participants were assigned randomly to treatment with either PRX-102 or Fabrazyme, both given every other week for up to two years.
Interim results reported in early June suggested that PRX-102 was at least as effective as Fabrazyme at slowing the decline in kidney function among participants who had completed at least one year of treatment.
PRX-102’s Phase 3 development program includes another ongoing Phase 3 clinical trial, called BRIGHT (NCT03180840), which is testing a monthly regimen for PRX-102 (at a dose of 2 mg/kg), rather than 1 mg/kg given every two weeks. The trial enrolled 30 participants who have been stably on other enzyme replacement therapies.
Protalix also is sponsoring two open-label extension studies to evaluate the long-term safety and efficacy of PRX-102 given with the every-other-week regimen (NCT03566017) and the once-a-month regimen (NCT03614234) in participants who complete other studies.
Last year, Protalix and Chiesi launched an expanded access program (NCT04552691) to provide pre-approval access to PRX-102 for people with Fabry disease in the U.S. who, in the opinion of their physician, lack satisfactory treatment options and/or are unable to participate in ongoing clinical trials.