Phase 3 Trial Shows Increased Stability of PRX-102 Over Other ERTs for Fabry Disease
PRX-102 (pegunigalsidase alfa) is safe for the treatment of patients with Fabry disease and has better stability over other available therapies, according to interim data from a Phase 3 clinical trial.
The most recent results from the trial were discussed during the 15th Annual WORLDSymposium 2019, recently held in Orlando, Florida. The oral presentation, “Once every 4 weeks — 2 mg/kg of pegunigalsidase alfa for treating Fabry disease; Preliminary results of a phase 3 study,” was presented by Holida D. Myrl, a physician assistant at the University of Iowa Health Care and BRIGHT study investigator.
PRX-102 is an investigational enzyme replacement therapy (ERT) designed by Protalix BioTherapeutics to compensate for the lack of alpha-galactosidase A (αGAL-A) enzyme in Fabry patients. This new ERT was developed from Protalix’s plant-based ProCellEx platform, which uses plant cells to produce therapeutic proteins, rather than the commonly used mammalian cells.
The Phase 3 trial (NCT03180840), called BRIGHT, was designed to evaluate the safety, efficacy, and overall stability and distribution in the body of PRX-102 in Fabry patients previously treated with ERT — Fabrazyme (agalsidase beta), marketed by Sanofi Genzyme, or Replagal (agalsidase alpha), by Shire.
To date, the study has enrolled 28 patients who received 2 mg/kg of PRX-102 administered every four weeks. Of these, 15 patients completed nine of the planned 12 months of treatment. Participants are still being recruited for an estimated total of 30; more information is available here.
Preliminary analysis revealed PRX-102 was stable and remained active in patients’ blood throughout the four-week period between infusions. In addition, PRX-102 was able to achieve about a sevenfold increase in blood concentrations 28 days after administration, compared with Fabrazyme (1 mg/kg every two weeks) 10 hours after infusion.
“The preliminary pharmacokinetic data from the BRIGHT study is very encouraging and suggest that PRX-102 has the potential to be effectively dosed every 4 weeks, compared to currently available enzyme replacement therapies (ERT) for Fabry disease which need to be administered every two weeks,” Holida said in a press release.
For reference, pharmacokinetics refers to the movement of a compound into, through, and out of the body, essentially how the body affects a medicine.
Evaluation of pre-existing antidrug antibodies before patients were switched to PRX-102 showed these had little to no effect on the circulating levels of PRX-102 during the four-week period. The levels of PRX-102 were higher than Fabrazyme even in the presence of these antibodies.
The new ERT was generally safe and well-tolerated by patients, with most reported adverse events mild to moderate in severity. The most common adverse events were infusion-related reactions and paresthesia (abnormal skin sensation).
Participants who complete the 52 weeks of treatment in the BRIGHT trial will have the opportunity to continue treatment with PRX-102 in an open-label extension study (NCT03614234). During this trial, researchers will evaluate the long-term efficacy and safety of PRX-102.