BRIGHT phase III trial for Fabry disease treatment

Protalix BioTherapeutics, Inc., a major biopharmaceutical company, and Chiesi Global Rare Diseases, a commercial unit of Chiesi Farmaceutici S.p.A., announced final results from the BRIGHT phase III clinical trial evaluating pegunigalsidase alfa (PRX-102) for the potential treatment of Fabry disease. The trial results indicate that treatment with 2 mg/kg of PRX-102 administered through intravenous (IV) infusion every four weeks was reasonably well-tolerated, and the health effects from Fabry disease were assessed by estimated glomerular filtration rate (eGFR) slope, as well as plasma lyso-Gb3 concentration, were stable.

“We are excited to share the final data from the BRIGHT study, an important milestone in the progress of our PRX-102 clinical program,” said Dror Bashan. He is Protalix’s president and chief executive officer. “The availability of this data for review by the US Food and Drug Administration, the European Medicines Agency and other regulators is another step forward towards the anticipated approval of PRX-102 as a potentially good alternative for adult Fabry patients in both the regular one mg\kg every two weeks as well as the two mg\kg every four weeks regimen.” he asserted.

PRX-102 is a plant cell-expressed recombinant known as PEGylated, cross-linked a-galactosidase-A product candidate. The BRIGHT phase III clinical trial (NCT03180840) was a  big, multicenter, multinational open-label. This switch-over study was designed to evaluate the treatment’s safety, efficacy, and pharmacokinetics, where 2 mg/kg of PRX-102 is administered every four weeks for 52 weeks, that is, a total of 14 infusions over a year. The study has enrolled 30 adult patients with Fabry disease, including 24 males and six females, with an average age of around 40.5 years and a standard deviation of about 11.3 years. The ages of patients ranged from 19 to 58 years. They had all previously received an approved enzyme replacement therapy (ERT) for three years or more on a stable dose administered every two weeks. The most common Fabry disease symptoms were acroparesthesia, angiokeratomas, heat intolerance, and hypohydrosis.

All these patients who have participated in the study received at least one dose of PRX-102, and all patients but one have already completed the study. Of these remaining 29 patients, 28 of them received the intended regimen of 2 mg/kg of PRX-102 every four weeks throughout the entire examination. In contrast, one particular patient was switched to 1 mg/kg of PRX-102 every two weeks per protocol from the 11th infusion. One patient had withdrawn from the study after the first infusion due to a traffic accident.

Overall, 33 of 182 total treatment-emergent adverse events (TEAEs) were in nine patients were considered to be treatment-related; all of these were mild or moderate in severity, and the majority of them were resolved at the time of the end of the study. There were no serious or severe treatment-related adverse events, and none led to death or study withdrawal. Of the treatment-emergent adverse events (TEAEs), 27 were infusion-related reactions (IRRs). The rest were single events of diarrhea, fatigue, erythema, influenza-like illness, increased urine protein and creatinine ratio, and white blood cells in urine. The 27 infusion-related reactions (IRRs) were reported in only five patients, who were all male.

Study outcomes also show that plasma lyso-Gb3 concentrations have remained stable during the study.

“We are pleased to announce final results from the BRIGHT phase III clinical trial and would like to thank the study investigators, Fabry disease patients, and their families who dedicated their time and efforts to this significant research,” claimed Giacomo Chiesi, who is head of Chiesi Global Rare Diseases. “Based on these data and additional clinical studies, we believe PRX-102 may be an important new treatment option for patients who are currently receiving ERT infusions every two weeks, and we look forward to advancing our work around the world to obtain regulatory approvals as quickly as possible and provide access to the Fabry disease community,” he added.