PRX-102 at least as effective as Fabrazyme, Interim Data Show
One year of treatment with PRX-102 (pegunigalsidase alfa), an investigational enzyme replacement therapy (ERT), was at least as effective as Fabrazyme (agalsidase beta) in preventing decline of kidney function in adults with dementia. Fabry, interim data from the BALANCE phase 3 clinical trial shows.
These results add to the growing body of clinical trial evidence supporting PRX-102, the first herbal ERT, every two weeks, as a potential new treatment option for Fabry patients.
“The BALANCE study is continuing as planned throughout its 24-month treatment period to support its final analysis,” Dror Bashan, Protalix BioTherapeutics“said the Chairman and CEO in a Press release. Protalix develops the PRX-102 in collaboration with Chiesi Rare Diseases Worldwide.
“Based on the entire clinical development program, which includes the BRIGHT and BRIDGE studies, we believe that PRX-102 has the potential to become an important treatment option for Fabry patients, both male and female,” said said Bashan.
Protalix and Chiesi plan to file an application with the European Medicines Agency (EMA) this year for approval of PRX-102 for the treatment of adults with Fabry disease.
A similar request was rejected by the U.S. Food and Drug Administration (FDA) in late April due to issues with facility inspections and manufacturing processes. The companies plan to request a Type A meeting with the FDA to discuss the way forward for PRX-102 approval.
“We look forward to the presentation of the [regulatory application] to the EMA for the European Union and to continue to work with the FDA towards US approval, ”Bashan said, adding that“ these regulatory milestones are our primary focus right now ”.
Like other ERTs, PRX-102 delivers alpha-galactosidase A, the enzyme missing in Fabry disease, directly into the bloodstream of patients. But the enzyme, made with Protalix’s plant-based ProCellEx platform, has been chemically modified to last longer in the body, potentially allowing less frequent dosing than existing ERTs.
The BALANCE Global Phase 3 Trial (NCT02795676) compares the safety and efficacy of PXR-102 versus Fabrazyme – an approved TES marketed by Sanofi Genzyme – in 78 adults with active renal failure.
Participants, all receiving Fabrazyme for at least one year prior to enrollment, were randomly assigned to either continue on Fabrazyme or switch to PXR-102 (1 mg / kg), both given every two weeks for two years maximum.
The primary objective of the trial is to assess whether PXR-102 is at least non-inferior to Fabrazyme in slowing the progression of kidney disease, as assessed by the mean annualized change in estimated glomerular filtration rate.
Secondary goals include changes in heart function, levels of disease biomarkers, pain, and analgesic use, as well as quality of life and safety measures.
The primary objective of the one-year interim analysis was to assess the non-inferiority of PXR-102 after at least one year of treatment.
The analysis was carried out on two predefined groups of patients: the intention-to-treat group, made up of all 77 patients who received at least one dose; and the per protocol group, made up of all 74 patients having completed at least one year of treatment.
The intention-to-treat group consisted of 47 men (61%) and 30 women (39%) with a mean age of 44.3 years.
Interim data showed that PRX-102 was at least not inferior to Frabazyme in slowing the decline of renal function in the group of patients who completed at least one year of treatment, but not in those who received at least one. dose.
At the time of analysis, two patients had left the trial due to adverse events, which were deemed to be treatment-related in one of them. No deaths occurred. Safety data appeared favorable and consistent with what was reported in previous clinical trials of PRX-102.
All patients will continue to receive treatment, regardless of which group they were assigned to, for up to two years. Final unblinded data is expected between April and June 2022.
BRIDGE and BALANCE
The completed BRIDGE evaluated the safety and efficacy of PRX-102 in 22 men and women with Fabry who were previously treated with Replagal (agalsidase alpha) for at least two years and at a stable dose for at least six months. .
The final results showed that PRX-102 was safe and caused patients to decline in renal function slower than that seen when receiving Replagal, achieving the primary objective of the trial.
The ongoing BRIGHT program is testing the safety, pharmacokinetics and efficacy of PRX-102 – at a more practical dose of 2 mg / kg, administered every four weeks for up to one year – in 30 Fabry patients previously treated with stable dose of a commercially available ERT every two weeks for at least three years. Pharmacokinetics refers to the movement of therapy in, through, and out of the body.
Initial trial data showed that the once-monthly regimen was well tolerated and effectively maintained patients’ renal function, biomarker levels and quality of life. Additionally, 75% of patients reported a reduction or stabilization in pain severity.
Final data from this trial, which is slated to end in December, is expected later this year.
Two open-label extension studies including patients treated with the PRX-102 bi-weekly regimen (NCT03566017) and once a month (NCT03614234) in BRIDGE, BALANCE and BRIGHT trials are currently underway.
“We thank the patients and clinicians participating in our completed and ongoing clinical studies evaluating PRX-102,” said Giacomo Chiesi, Director of Chiesi.
“While we are planning [regulatory application] submission in the EU, we remain committed to advancing our US PRX-102 development program while making access to therapy accessible to eligible patients through our expanded access program in the US ”, Chiesi added.
Launched in October, this extended access program (NCT04552691) provides pre-approval access to PRX-102 to US patients who, in the opinion of their physician, do not have satisfactory treatment options and / or could not participate in ongoing Fabry trials.