HIGH IMPACT Protalix and Chiesi announce topline results of Phase III BALANCE trial evaluating the safety and efficacy of PRX-102 in Fabry.

  • Study:
    • Phase III BALANCE study is a 12-month, randomized, double-blind, study of 1 mg/kg PRX-102 administered every two weeks compared to agalsidase beta.
    • 78 enrolled patients were previously treated with agalsidase beta for at least one year with an eGFR slope at screening worst than -2 ml/min/1.73 m2/year.
    • Patients were randomized on a 2:1 ratio for switching to PRX-102 (n=52) or continuing on agalsidase beta (n=25).
  • Efficacy:
    • The median eGFR slope in the PRX-102 arm was –2.514 mL/min/1.73 m2/year and -2.155 mL/min/1.73 m2/year (–3.805, –0.505) in the agalsidase beta arm, demonstrating a large overlap in the confidence intervals of the two arms.
    • The prespecified non-inferiority margin was met with difference in medians being -0.359 mL/min/1.73 m2/year.
    • Topline results in the Per Protocol (PP) analysis set (72 patients) are consistent with the Intent–to–Treat (ITT) results.
  • Safety:
    • 47 (90.4%) patients in the PRX–102 arm experienced at least one AE compared to 24 (96.0%) in the agalsidase beta arm.
      • The number of events adjusted to 100 years of exposure is 572.36 events for the PRX–102 arm and 816.85 events for the agalsidase beta arm.
    • TRAEs were reported for 21 (40.4%) patients in the PRX–102 arm compared to 11 (44.0%) in the agalsidase beta arm.
      • The number of treatment-related events adjusted to 100 years of exposure is 42.85 events for the PRX-102 arm and 152.91 events for the agalsidase beta arm.
    • For PRX-102 arm, 18 (24.6%) patients were ADA-positive at baseline and 17 (94.4%) had neutralizing antibody activity.
    • For the agalsidase beta arm, 8 (32.0%) patients were ADA-positive at baseline, of which 7 (87.5%) had neutralizing antibody activity.
    • At the end of the two-year study, 11 (23.4%) patients receiving PRX-102 were ADA-positive, of which 7 (63.6%) had neutralizing antibody activity, while in the agalsidase beta arm 6 (26.1%) were ADA-positive and all 6 (100%) had neutralizing antibody activity.
    • 6 patients discontinued from the study: 5 (.94%) from PRX-102 arm with 1 withdrew prior to first infusion, 2 due to personal reasons, and 2 due to AEs. 1 patient (4%) from the agalsidase beta arm discontinued due to personal reasons.
  • Next steps:
    • 69 patients from the trial have opted to continue receiving PRX-102 1mg/kg every other week in a long-term open-label extension study.
    • Protalix believes the totality of data from BALANCE trial and BRIGHT study supports favorable benefit-risk profile for the treatment of Fabry and plans to resubmit BLA to the FDA.

inThought Analysis

With the change in regulatory landscape in the U.S with the full approval of Fabrazyme (agalsidase beta) in March 2021, the primary analysis of PRX-102’s BALANCE study was changed from superiority to non-inferiority. PRX-102 was also issued a CRL last year partly due to the approval of Fabrazyme and was no longer eligible for accelerated approval. Given the non-inferior data, if approved, PRX-102 will likely capture a significant number of Fabry patients with its favorable frequency of dosing and immunogenicity over Fabrazyme.


Source: Protalix Press Release