Interim data from BRIDGE Phase III study of PRX 102 shows efficacy in Fabry disease.- Protalix BioTherapeutics

Protalix BioTherapeutics announced positive 12-month on-treatment data from the first 16 out of the 22 adult patients with Fabry disease enrolled in its BRIDGE Phase III study of PRX 102 (pegunigalsidase alfa). The BRIDGE study is an open label switch-over study evaluating the safety and efficacy of pegunigalsidase alfa, 1 mg/kg infused every two weeks, in up to 22 Fabry patients currently treated with agalsidase alfa (Replagal) for at least two years and on a stable dose for at least six months. Patients are screened and evaluated over three months while continuing agalsidase alfa treatment. Following the screening period, each patient was enrolled and switched from Replagal treatment to receive intravenous (IV) infusions of pegunigalsidase alfa 1 mg/kg every two weeks for 12 months.

Patients have the option to receive pegunigalsidase alfa infusions in a home care setting based on infusion tolerability and country regulation. The 12-month interim data from the first 16 of 22 adult patients enrolled (9 males and 7 females) demonstrate a mean improvement in kidney function, in both male and female patients, when switched from agalsidase alfa to pegunigalsidase alfa. One hundred percent of the progressing patients, those with an estimated Glomerular Filtration Rate (eGFR) slope between -5 and -3 mL/min/1.73 m2/year, and 66.7% in the fast progressing group, with an eGFR slope < -5 mL/min/1.73 m2/year, achieved the proposed therapeutic goals goals (eGFR slope at least -3 mL/min/1.73 m2/year for progressing patients, and at least -5 mL/min/1.73m2/year or more than 50% decrease in progression for fast progressing patients) after switching to pegunigalsidase alfa. The majority of the patients who completed the study rolled over to a long-term extension study, continuing to be treated with pegunigalsidase alfa.

In the study, after one year, the mean annualized eGFR slope improved from -5.10 mL/min/1.73m2/year while on agalsidase alfa to -0.23 mL/min/1.73m2/year on pegunigalsidase alfa. Baseline characteristics of these patients, ages 27 to 60 years, were: mean eGFR 75.45 in males and 85.78 mL/min/1.73m2 in females, annualized pre-switching eGFR slope was -5.04 and -5.18 mL/min/1.73m2/year, in males and females respectively, mean residual leucocytes enzymatic activity 5.9% of lab normal mean in males and 27.9% in females, and plasma lyso-Gb3 mean levels 53.6 and 13.8 nM, in males and females, respectively. Pegunigalsidase alfa was found to be well tolerated in the study, with all adverse events being transient in nature without sequelae.

Comment: pegunigalsidase alfa is an investigational, plant cell culture expressed enzyme, and a chemically modified stabilized version of, the recombinant alpha-Galactosidase-A protein. Protein sub-units are covalently bound via chemical cross-linking using short PEG moeity, resulting in a more stable molecule with different pharmacokinetic parameters compared to the current available versions of the enzyme. In clinical studies, pegunigalsidase alfa has been observed to have a favorable circulatory half-life of approximately 80 hours.