Study: Pegunigalsidase alfa noninferior to agalsidase beta in slowing eGFR decline
Key takeaways:
- At 2 years, median eGFR slope difference between groups was 0.36 mL/min/1.73 m2 per year.
- Exposure-adjusted rates were 7.8-fold higher with pegunigalsidase alfa.
Pegunigalsidase alfa was noninferior to agalsidase beta in slowing the rate of eGFR decline during a 2-year period and had lower rates of adverse events and infusion reactions, according to recently published data.
In the phase 3 BALANCE trial, researchers compared pegunigalsidase alfa, a PEGylated alpha-galactosidase A enzyme replacement therapy, with agalsidase beta in adults with Fabry disease. Overall, 77 patients with an annualized eGFR slope more negative than 2 mL/min/1.73 m2 per year were included, with 52 patients receiving pegunigalsidase alfa and 25 patients receiving agalsidase beta for at least 1 year. Baseline eGFR was 74.5 mL/min/1.73 m2, and median eGFR slope was 7.3 mL/min/1.73 m2 per year.
Fabry disease “involves many systems, including renal, cardiac, neurologic and cerebrovascular,” Eric L. Wallace, MD, of the department of medicine and division of nephrology at The University of Alabama at Birmingham, wrote with colleagues. At the time of the study, three “treatment options were approved with varying availability by country, including two enzyme replacement therapies ... and one oral pharmacological chaperone therapy. BALANCE is the first study to directly evaluate efficacy, safety and tolerability of pegunigalsidase alfa [vs.] agalsidase beta in adult patients with previous agalsidase beta treatment and deteriorating renal function.”
Patients were randomly assigned in a 2:1 ratio to either 1mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary outcome measured noninferiority based on median annualized eGFR slope differences between treatment arms.
At 2 years, the median eGFR slope difference between groups was 0.36 mL/min/1.73 m2 per year, meeting noninferiority criteria, according to the study. Researchers also noted minimal changes in lyso-Gb3 concentrations in both treatment arms at the end of the trial.
The number of patients who had treatment-related adverse events and mild or moderate infusion-related reactions was similar in each group. Exposure-adjusted rates were 3.6- and 7.8-fold higher, respectively, with agalsidase beta than with pegunigalsidase alfa.
Researchers also found antibodies in 15% of patients on pegunigalsidase alfa and in 26% of patients on agalsidase beta. No deaths occurred during the study.
“BALANCE demonstrated noninferior renal efficacy and the potential for improved tolerability with pegunigalsidase alfa compared with agalsidase beta in patients with Fabry disease and deteriorating renal function,” Wallace and colleagues wrote.
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