Protalix’s PRX-102 Seen to Halt Kidney and Heart Decline in Long-Term Phase 1/2 Trial

Two-year data from Protalix BioTherapeutics’ Phase 1/2 extension trial of PRX-102 (pegunigalsidase alfa) show that the treatment prevented a decline in kidney and heart function in Fabry disease patients.

People in this small, open-label study also reported a significant reduction in the severity of their symptoms. The data support the possibility of substantial benefit to Fabry patients, as well as the treatment’s continuing evaluation in three Phase 3 studies now enrolling.

“The long-term results at 24 months indicate that PRX-102 continues to demonstrate a remarkable improvement and stability across all key Fabry disease parameters,” Raphael Schiffmann, a professor at the Baylor Research Institute in Dallas, said in a press release.

The extension study (NCT01981720) recruited patients who had received PRX-102 in the original Phase 1/2 trial (NCT01678898), or a shorter term extension study (NCT01769001).

Eleven of the 16 patients in the original study continued the intravenous infusion treatment for two years. Those who dropped out did so because they either became pregnant or moved from the area, researchers said.

At two years, patients had a decrease of about 90 percent in their levels of globotriaosylsphingosine (LysoGb3) — one of the fatty substances accumulating in Fabry disease patients.

Researchers noted no decrease in kidney or heart function, and no development of heart fibrosis. Moreover, patients improved on all assessed gastrointestinal symptoms, including the severity and frequency of abdominal pain and diarrhea.

An improvement in overall disease severity of 40 percent was also measured, using a tool called the Mainz Severity Score Index. Patients improved on all aspects of the disease, the measure showed.

“PRX-102 was also well tolerated, with a very low incidence of treatment-induced anti-drug antibodies that were reversible with only a transient and reversible effect on pharmacokinetics,” Schiffmann said.

Pharmacokinetics are measures of how a medication is processed in the body.

Study findings showed that most adverse events were either mildly or moderately severe. After one year, fewer than 19 percent of patients had formed antibodies to the medication, and only two of them — less than 13 percent — had so-called neutralizing antibodies. Neutralizing antibodies may render the treatment ineffective.

Importantly, the antibodies disappeared over time in all affected patients. Researchers also did not note any impact of the antibodies on the treatment’s effectiveness or safety.

“These long-term results further support that PRX-102 has the potential to be a significant differentiated therapy when compared to currently approved enzyme replacement therapies, and carries an important hope for all Fabry patients,” said Schiffmann.

PRX-102 is currently investigated in three Fabry disease Phase 3 clinical trials (NCT03180840, NCT02795676, and NCT03018730). These trials — all taking place across the U.S. and Europe, and occasionally elsewhere — are recruiting participants. Interested patients can find more information, including locations and contact details, by following the links above.

“The need for better treatments to address Fabry disease remains great, and Protalix, together with our European partner, Chiesi Farmaceutici, look forward to introducing an anticipated new therapy to the market,” said Moshe Manor, Protalix’s president and CEO.

The European Commission designated PRX-102 an orphan drug for the treatment of Fabry disease, signaling that regulators consider it a potential substantial improvement over current therapies.

In contrast to the available versions of enzyme-replacement therapies, PRX-102 is a chemically modified enzyme. The modifications make the therapy more stable and active, Protalix reports.