Protalix and Chiesi Get FDA OK to Seek Accelerated Approval of PRX-102 for Fabry Disease

PRX-102 (pegunigalsidase alfa), an investigational enzyme replacement therapy (ERT) for Fabry disease, is closer to accelerated approval after a successful pre-biologics license application (BLA) meeting with the U.S. Food and Drug Administration (FDA), according to a press release.

PRX-102’s developers, Protalix BioTherapeutics and Chiesi Farmaceutici, met with the FDA on Oct. 15, during which they discussed the terms of submitting a BLA for PRX-102 under accelerated approval for the treatment of people with Fabry disease.

The regulatory agency indicated that existing data will support the BLA and no additional clinical trials are necessary before submission.

As a result, the companies are now finalizing their application based on available data from Phase 1/2 clinical trials of PRX-102 (NCT01678898 and NCT01769001) and from the ongoing Phase 3 BRIDGE study (NCT03018730). They expected to submit the BLA in April 2020.

“We have now had three successful interactions with the FDA during 2019, which built on our long-term relationship with the Agency and made our regulatory path forward for pegunigalsidase alfa clear,” said Einat Almon, Protalix’s senior vice president of product development. “We expect that alignment with the FDA on the Accelerated Approval pathway for pegunigalsidase alfa results in our being significantly closer to bringing an approved product to market to help Fabry patients.”

PRX-102 is being developed to compensate for the lack of alpha-galactosidase A (αGAL-A) enzyme in Fabry patients. Th investigational ERT was created from Protalix’s plant-based ProCellEx platform that uses plant cells to produce therapeutic proteins, rather than the commonly used mammalian cells, which can pose safety issues.

Previous data from Phase 1/2 studies showed that PRX-102 was considered safe and was able to prevent a decline in kidney and heart dysfunction in Fabry patients.

PRX-102 is currently being studied globally in three Phase 3 trials: BALANCE (NCT02795676), BRIGHT (NCT03180840), and BRIDGE studies.

Preliminary results from the BALANCE study demonstrated that PRX-102 is superior to currently available therapy Fabrazyme (agalsidase beta, developed by Sanofi Genzyme) in stabilizing kidney function, and is less suppressed by pre-existing neutralizing antibodies.

Data from the BRIGHT study has so far shown that PRX-102 is able to achieve roughly seven times higher blood concentrations within 28 days after administration than Fabrazyme.

The open-label Phase 3 BRIDGE study is evaluating the safety and impact of PRX-102 in Fabry patients previously treated with Replagal (agalsidase alpha, marketed by Shire) for at least two years.

Preliminary data of the first 16 of 22 enrolled patients who completed 12 months of treatment showed that PRX-102 significantly improved patients’ kidney function by reverting the decline in glomerular filtration rate (eGFR) — a measure of how well the kidneys are cleaning the blood — over one year.

One year of treatment with PRX-102 significantly improved the clinical status of all patients with progressing disease and 66.7% of those with fast-progressing disease. Moreover, PRX-102 was well tolerated and generally safe; all adverse events reported during the study were temporary and did not cause additional health problems.

Most of the patients who completed the study chose to continue treatment with PRX-102 through a long-term extension study (NCT03566017).

“The confirmation by the FDA regarding the proposed BLA submission, together with the finalization of the BALANCE study enrollment (78 patients) and the very promising interim results from the BRIDGE study, are three recent significant consecutive milestones achieved with respect to our Fabry late-stage clinical program,” said Dror Bashan, Protalix’s president and CEO. “We are committed to the completion of this program with positive results for the benefit of the Fabry patient community.”

For a BLA approved under accelerated approval to be converted into a full approval, a confirmatory trial is necessary. In this case, the BALANCE study will serve as the confirmatory trial.

“Together with our partner Chiesi, we look forward to completing the application process, as well as continuing with our double blind head-to-head phase III BALANCE clinical trial, which we feel will further strengthen the position of pegunigalsidase alfa within the Fabry patient community,” Almon said.

Chiesi Farmaceutici previously acquired the exclusive rights to develop and market PRX-102 in the United States.