Protalix BotherRepoytics, Inc. (NYSE American and TASE: PLX) A biopharmaceutical company focusing on the development, production and commercialization of therapeutic recombinant proteins produced using a unique plant-friendly expression and production system, called ProCellEx®, together with its partner in development and commercialization, Casey’s Rare Diseases Division, Services Group Research-focused international health today released positive topline results from the BRIGHT Phase III clinical study examining alpha-pegoniglycidase (PRX-102), at a dose of 2 mg / kg body weight given every four weeks as a potential treatment for Fabry disease.
PRX-102 is a company-developed drug, made from a recombinant protein, alpha-galactosidase-A (cross-linked α-galactosidase-), extracted from plant cells that have undergone chemical pegylation after extraction (PEGylated).
The BRIGHT study is a 12-month Phase III clinical trial in open indication and switch-over therapy designed to evaluate the safety, efficacy, and pharmacokinetics of PRX-102 therapy, at a dose of 2 mg per kilogram of body weight every four days. Weeks for up to 30 patients with Fabry disease previously treated with a commercially available enzyme replacement drug (ERT) (alpha-sedase alpha – Replagal® or agla-acidase beta – Fabrazyme®) for at least three years and in a stable dose given every two weeks.
The topline results indicate that PRX-102 given at a dose of 2 mg per kg of body weight by intravenous infusion every four weeks was well tolerated by the patients who received it and clinical stability was maintained which was maintained in adult Fabri patients. None of the new patients developed antibodies to the drug as a result of the treatment (ADA) following the switch to PRX-102.
“We are excited to announce the topline results of the BRIGHT study, which is our third consecutive clinical trial in PRX-102 that ends in positive results, after Phase I / II and BRIDGE clinical trials. Adults with Fabry disease, “she said Dr. Einat Brill Almon, Senior Vice President and Chief Development Officer of Protelix. “We are encouraged to note that all patients who completed this study chose to join the long-term follow-up study. To date, 80% of patients enrolled in the BRIGHT study have been treated with this treatment regimen for two years. We look forward to furthering the study and evaluating the results once again.”
“The results illustrate the potential of PRX-102 to become an important therapeutic alternative for the Fabri patients community and that a 2 mg PRX-102 treatment regimen per kilogram every four weeks may offer significant benefits to both patients and physicians. The attending physicians will be happy with a therapeutic regimen “Another potential and well tolerated that they could offer to Fabry patients subject to the approval of the PRX-102,” he said. Dror Bashan, President and CEO of Protelix. “We are pleased with our solid balance sheet that supports the development efforts and look forward to the implementation of a year rich in milestones that will contribute to bearing the value of the company.”
The BRIGHT study included 30 cow patients (24 men and 6 women). The most common symptoms / manifestations of Fabri’s disease included circumcision, fever intolerance, angiocartomas and hypohydrosis. All 30 patients received at least one dose of PRX-102 and 29 patients (mean age 40.5) [סטיית תקן 11.3], Ranging from 19 to 58 years) completed a 12-month study. Of these 29 patients, 28 received the designated drug regimen of 2 mg / kg every four weeks throughout the study and one patient was transferred to a 1 mg dose of PRX-102 per kg every two weeks according to the protocol. One patient withdrew from the study after the first transfusion due to a car accident.
Following screening tests, patients were recruited and switched from ERT-treated to intravenous infusion of 2 mg / kg PRX-102 every four weeks for 52 weeks (14 infusions in total). The first infusion of PRX-102 was given under controlled conditions. Based on the criteria outlined in the protocol, patients were able to receive the PRX-102 infusions in home care after the researcher and the medical monitor (Sponsor Medical Monitor) agreed that performing an infusion under such conditions was safe.The safety and effectiveness research objectives were tested throughout the 52 weeks of the trial.
The study outcome measures showed that plasma lyso-Gb3 concentrations remained stable throughout the study with a mean change of 3.01 nM from baseline (19.36 nM) to week 52 (22.23 nM). The absolute mean change in eGFR values remained stable during the 52-week treatment period with a mean change from baseline of -1.27 mL / min / 1.73 m2.
“Patients participating in the BRIGHT study expressed their satisfaction with the treatment regimen every four weeks,” he said. Dr. John Bernat of the University of Iowa and lead researcher in BRIGHT research. “An infusion of 2 mg per kg every four weeks may allow patients to maintain clinical status while reducing by half the number of treatments.”
Patients ‘responses to the survey conducted with the EQ-5D-5L Quality of Life Questionnaire indicate that patients’ self-perception of health remained high and stable during the 52-week study with an overall health score (SE) of 78.3 (3.1) and 82.1 (2.9) at baseline and per week 52, respectively, on a scale of 0 to 100. Using a short Brief Pain Inventory (BPI) questionnaire, approximately 75% of study participants felt improvement or no change in the mean pain severity at week 52 (compared to baseline). The influencing factors appearing in the questionnaire also remained stable throughout the study. Pain-related results indicate that there was no increase and / or recurrence of pain. No clinical events related to Fabry disease have been reported during the study.
“Of the 30 patients who participated, 20 remained negative for neutralizing antibodies throughout the course of treatment. Of the 10 patients who were initially positive for antibodies to the drug, four became negative for neutralizing antibodies at 12 months, a fact that suggests the development of tolerance (toleration) of these patients,” D added. Mr. Almon. These immunogenicity data are highly encouraging and support the PRX-102 benefit-risk profile.
“On behalf of Casey’s staff, we thank patients, their families and researchers for their time and research participation,” he said. Giacomo Casey, who heads Casey’s Rare Diseases Division. “Their dedication has helped advance this Phase III study and the topline data are another important milestone in our joint effort to make PRX-102 available to Fabry patients as soon as possible.”
The company intends to publish the final data from the BRIGHT study in the second half of 2021 and present them at an appropriate medical conference.