Monthly Elfabrio treatment keeps Fabry disease stable for 5 years
Extension study data show dosing regimen generally safe
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Elfabrio (pegunigalsidase alfa), when given every four weeks, was generally safe and helped most Fabry disease patients maintain stability for up to five years. The therapy was particularly effective for women and those who did not develop antibodies against the replacement enzyme.
That’s according to interim results of the ongoing BRIGHT F51 open-label extension study (NCT03614234), which is testing the long-term efficacy and safety of Elfabrio at 2 mg/kg of body weight every four weeks in 29 adults with Fabry disease who had already received the enzyme replacement therapy for one year, at this dosing schedule, as part of the Phase 3 BRIGHT (NCT03180840) trial.
The therapy is approved in the U.S. for adults with Fabry disease as an intravenous (into-the-vein) infusion at 1 mg/kg body weight every two weeks, and was recently approved in the European Union under the new every-four-week dosing regimen.
The study, “Long-term efficacy and safety of pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease: results from up to 5 years of the BRIGHT F51 phase III, open-label extension study,” was published in the Orphanet Journal of Rare Diseases. It was funded by Protalix Biotherapeutics and Chiesi Farmaceutici, which developed Elfabrio, now marketed by Chiesi.
As an enzyme replacement therapy, Elfabrio provides alpha-galactosidase A (alpha-Gal A), an enzyme missing or nonfunctional in Fabry, to reduce the build-up of fatty molecules that cause Fabry symptoms.
Study, extension results support less frequent dosing schedule
The European Commission’s approval of the new dosing regimen was based on positive results from the BRIGHT study and its open-label extension, which assessed the safety and effectiveness of the less frequent dosing schedule in patients with stable disease.
The BRIGHT trial showed that this schedule was generally safe and effective in 30 patients who had been on other replacement therapies. Of the 30 patients, 29 enrolled in the open-label extension study to continue receiving Elfabrio for up to an additional seven years. One patient withdrew due to fatigue, leaving 28 continuing patients who have received Elfabrio for three to five years. The total durations are different because patients joined the extension study at different times.
Kidney function was measured using the estimated glomerular filtration rate (eGFR), which assesses how well the kidneys filter blood. There was a decline in median annual eGFR, which was faster in men than in women. Patients with antibodies against the replacement enzyme, an immune response to the therapy, had a faster decline than those without.
Protein in the urine remained mostly normal or only slightly elevated in most patients. Some patients, particularly those with pre-existing antibodies, required dose adjustments due to worsening kidney function or pain crises. Blood lyso-Gb3, a biomarker of Fabry disease, remained low in women and showed only mild changes in men. Patients with antibodies against the replacement enzyme tended to have higher levels of lyso-Gb3 in their blood.
Overall disease severity, measured by the Mainz Severity Score Index (MSSI), remained stable, especially in patients without pre-existing antibodies, and most patients (81.8%) experienced either reduced or unchanged pain after about four years. Quality of life, measured by the EuroQol 5-Dimension 5-Level questionnaire, also improved slightly.
Elfabrio was generally well tolerated. Most side effects were mild or moderate, and only a small proportion were related to the enzyme replacement therapy. Infusion-related reactions, such as fever or chills, occurred in about one-third of patients (31%), mostly early in treatment, and were mild or moderate. Infusions became faster over time, decreasing from an average of 4.5 hours at baseline to two hours after one year.
While these results suggest that extending the dosing interval of Elfabrio to every four weeks is feasible and effective for many patients, “the final results of this extension study will further assess the feasibility of this dosing regimen,” the researchers wrote. In the meantime, they said, “clinical outcomes should be closely monitored.”
