PRX-102 Safe and Effective Once Monthly Fabry Treatment, Phase 3 Data Show

A once-a-month regimen of the investigational enzyme replacement therapy (ERT) PRX-102 (pegunigalsidase alfa) is safe and effective at maintaining disease stability in adults with Fabry disease, top-line data from the BRIGHT Phase 3 trial show.

All were previously being treated twice a month with a commercially available ERT.

“Patients participating in the BRIGHT study have expressed their satisfaction with the once every four weeks regimen,” John Bernat, MD, PhD, the trial’s principal investigator at the University of Iowa’s site, said in a press release.

“Infusions of 2 mg/kg once every four weeks has the potential to enable patients to maintain their clinical status while reducing their number of treatments by half,” Bernat added.

Final data from BRIGHT are expected to be announced in the second half of the year, and to be presented at a future medical conference.

“We are excited to share these top-line results from the BRIGHT study, our third consecutive positive clinical trial of PRX–102, following the Phase I/II and the BRIDGE [Phase 3] clinical studies,” said Einat Brill Almon, PhD, Protalix BioTherapeutics’ senior vice president and chief development officer. Protalix is developing PRX-102 in collaboration with Chiesi Global Rare Diseases.

“The results indicate that this investigational therapy is well tolerated and potentially an effective treatment for adult patients living with Fabry disease,” Almon said, adding that the company looks forward to “further evaluating the results.”

Made with Protalix’s plant-based ProCellEx platform, PRX-102 delivers a modified version of alpha-galactosidase A (Gal A) — the missing enzyme in Fabry disease — that is meant to last longer in the body, requiring less frequent dosing than existing ERTs. It is administered directly into the bloodstream.

The therapy is currently being reviewed by the U.S. Food and Drug Administration under priority status as a potential treatment for adults with Fabry disease, with a decision due by April 27. A similar regulatory application is expected to be filed to the European Medicines Agency.

The BRIGHT trial (NCT03180840) evaluated the safety, pharmacokinetics, and effectiveness of PRX-102 — at a dose of 2 mg/kg, given every four weeks for up to one year — in 30 Fabry patients previously treated with a stable dose of a commercially available ERT every other week for at least three years.

Pharmacokinetics refers to the therapy’s movement into, through, and out of the body. Available ERTs included Sanofi Genzyme’s Fabrazyme (agalsidase beta) and Takeda’s Replagal (agalsidase alpha), which is not currently approved in the U.S.

All participants (24 men and six women) received at least one dose of PRX-102, and 29 of them (mean age of 40.5, ranging from 19 to 58) completed the one-year treatment period. In agreement with the trial’s protocol, treatment was changed to 1 mg/kg of PRX-102, given every two weeks, in one patient due to clinical deterioration.

Initial PRX-102 doses were administered under controlled conditions at the investigation site. But patients were able to infuse the treatment at home once the investigator and sponsor medical monitor agreed it was safe to do so and home care setup adequate.

BRIGHT’s top-line results showed the therapy to be well-tolerated, with patients’ lyso–Gb3 levels — a biomarker of Fabry disease — and kidney function remaining stable throughout the study. Participants’ perception of their own health also remained high and stable through the one-year treatment, as assessed with the validated Quality of Life EQ-5D-5L questionnaire.

About 75% of participants also reported a reduction or stabilization in pain severity after one year of treatment, and additional pain-related results indicated that there was no increase or relapse in pain. No Fabry clinical events were reported during the study.

At study’s start, 10 patients were positive for immune antibodies against the therapy-delivered Gal A enzyme, which can limit the ERTs’ effectiveness.

After switching to PRX-102, four of these patients became negative for such antibodies, and no other trial participant developed anti-drug antibodies at one year of treatment, “suggesting tolerization by these patients,” Almon said.

“We find this [immune-related] data very encouraging and supportive to the positive benefit-risk profile of PRX-102,” she added.

These findings indicate that PRX-102’s once-a-month regimen was well tolerated and effectively maintained a stable clinical presentation in adults, highlighting “the potential of PRX–102 to be an important treatment option for the Fabry community,” said Dror Bashan, Protalix’s president and CEO.

All 29 patients completing treatment entered the open-label extension study (NCT03614234), in which they will continue PRX-102 treatment for up to three years or until the therapy becomes commercially available.

“Currently, 80% of the patients enrolled in the BRIGHT study have been treated with this treatment regimen for over two years,” Almon said.

Giacomo Chiesi, Chiesi Global Rare Diseases’ head, thanked all involved in BRIGHT for helping to move the Phase 3 program forward. “[T]hese top-line data are another important milestone in our collected effort to make PRX-102 available to Fabry patients in need as rapidly as possible,” Chiesi added.

In addition to BRIGHT, PRX-102’s Phase 3 development program includes two other Phase 3 trials with completed enrollment — BRIDGE (NCT03018730) and BALANCE (NCT02795676).