FDA Meeting Likely to Lead to New Request for PRX-102 Approval

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by Steve Bryson PhD |

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A recent type A meeting with the U.S. Food and Drug Administration (FDA) is likely to lead Protalix Biotherapeutics to resubmit a request for approval of PRX-102 (pegunigalsidase alfa) to treat Fabry disease, after its initial application was rejected by the agency.

“We are pleased with the results of the Type A meeting,” Dror Bashan, Protalix’s president and CEO, said in a press release. “We remain committed to the Fabry community and our goal of providing an alternative treatment option for Fabry patients.”

PRX-102, a plant-based enzyme replacement therapy the company is developing in collaboration with Chiesi Global Rare Diseases, is designed to deliver a long-lasting lab-made version of alpha-galactosidase A, the enzyme lacking in Fabry patients.

The companies applied to the FDA last year, asking for accelerated approval of PRX-102, which the agency accepted under priority review. However, the FDA rejected the application in April due to problems with the manufacturing process and facility inspections, caused in part by pandemic travel restrictions. Problems identified were not related to the therapy’s effectiveness or safety.

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Protalix then requested a type A meeting to discuss a path forward for PRX-102’s approval.

In the Sept. 9 meeting, the FDA agreed in principle that the data package it received from the companies had the potential to support a standard approval of PRX-102, Protalix stated, citing the meeting’s minutes provided by the regulatory agency.

“We are encouraged by the productive discussion with the FDA, which we believe provides a pathway to resubmit the PRX-102 BLA, and appreciate the valuable feedback and guidance provided,” said Einat Brill Almon, PhD, senior vice president and chief development officer at Protalix.

“We look forward to our continued development of PRX-102 and our collaborative efforts with Chiesi in advancing the PRX-102 program towards commercialization,” Almon added.

The planned resubmission is expected to include final, two-year data from the Phase 3 BALANCE clinical trial (NCT02795676), comparing the therapy’s safety and effectiveness to Fabrazyme (agalsidase beta), an approved enzyme replacement therapy by Sanofi Genzyme.

The ongoing trial, which recently completed dosing its last patient, enrolled 78 adults with Fabry who were previously treated with Fabrazyme for one year and had progressive kidney decline. Participants were randomly assigned to continue on Fabrazyme or switch to PRX-102, both given every two weeks for up to two years.

Results after one year of treatment showed that PRX-102 was at least as effective as Fabrazyme at slowing kidney function decline. BALANCE is set to conclude in May, with final data expected a month later.

A total of 72 patients completed the two-year treatment period, with two patients stopping treatment early due to side effects and four others for personal reasons. Of those who completed treatment as of mid-October, 67 chose to continue or start with PRX-102, given at 1 mg/kg every other week, in an open-label extension study.

The therapy’s development program includes two other Phase 3 trials — BRIDGE (NCT03018730) and BRIGHT (NCT03180840) — as well as two open-label extension studies testing the long-term impact of PRX-102 given every other week at 1 mg/kg (NCT03566017), or once a month (NCT03614234) at a 2 mg/kg dose.

Protalix and Chiesi started an expanded access program (NCT04552691) last year to allow pre-approved access to PRX-102 for Fabry patients in the U.S. who lack adequate treatment options and/or are unable to join clinical trials.

Protalix and Chiesi also announced an Oct. 8 meeting with the European Medicines Agency (EMA), an essential step in the process for a planned filing of an approval application. The companies discussed details of the application, and reported that EMA members were “generally supportive.”

Chiesi and Protalix expect to submit an approval application for PRX-102 to the EMA early in 2022.

“On behalf of our team at Chiesi, we thank the patients, families and clinicians for their participation in our clinical studies evaluating PRX-102,” said Giacomo Chiesi, head of Chiesi Global Rare Diseases. “We remain committed to advancing this important program to expand support for the Fabry disease community.”