Less frequent Elfabrio ERT regimen for Fabry up for EU approval
Application seeking every 4 week treatment instead of approved every 2
The European Medicines Agency (EMA) has validated a regulatory application that seeks clearance of a less frequent regimen of Elfabrio (pegunigalsidase alfa), an approved enzyme replacement therapy (ERT) for adults with Fabry disease.
If the agency decides to approve the variation application after its review, Fabry patients in the European Union could start receiving the therapy once every four weeks, at a dose of 2 mg/kg, instead of the currently approved every-other-week regimen, now given at a dose of 1 mg/kg.
“The validation of this variation application is an important milestone in our efforts to reduce the burden of treatment for some adult patients living with Fabry disease who continue to experience unmet medical needs,” Giacomo Chiesi, executive vice president of Chiesi Global Rare Diseases, which codeveloped the therapy with Protalix Biotherapeutics, said in a joint company press release.
The now-validated application was based on new pharmacological models and analyses, as well as data from the Phase 3 BRIGHT clinical trial (NCT03180840) and its ongoing open-label extension study (NCT03614234).
Results from BRIGHT, which involved 30 Fabry patients who had previously been on other ERTs — all administered every two weeks — showed that one year of treatment with Elfabrio’s less frequent regimen was generally safe and effective.
Dror Bashan, president and CEO of Protalix, said the new regimen would give Fabry patients more choices.
“Based on study results, we believe in the potential of [Elfabrio] 2 mg/kg administered every four weeks to be a beneficial, alternative dosing option for some adults living with Fabry disease,” Bashan said. “We look forward to continuing to work closely with the agency in the months ahead.”
EU agency validates application seeking OK for new Elfabrio dosing regimen
A rare genetic disease, Fabry is caused by a faulty or missing alpha-galactosidase A (alpha-Gal A) enzyme. As a result, fatty molecules, mainly globotriaosylceramide (Gb3), build up within cells, progressively damaging organs, particularly the kidneys, heart, and nervous system. This causes a diverse range of Fabry disease symptoms.
For more than two decades, enzyme replacement therapy, known as ERT for short, has been the standard treatment for Fabry. It delivers a working alpha-Gal A enzyme directly into the patient’s bloodstream to promote Gb3 breakdown, and ultimately slow or prevent disease progression.
Elfabrio is an ERT approved for Fabry disease that’s been modified to make the enzyme more stable in the blood, and stay longer in the body. The therapy is administered as an intravenous, or into-the-vein, infusion every two weeks at a dose of 1 mg/kg.
We remain committed to meeting the needs of people with Fabry disease and bringing additional therapeutic options to market.
The one-year BRIGHT study tested whether a less frequent, but higher dose of the drug was safe for Fabry patients who had stable disease with other ERTs. The results showed that Elfabrio, when given once every four weeks at a dose of 2 mg/kg, was detected in the bloodstream at effective levels throughout the four-week interval period.
Additionally, kidney function, as well as Fabry disease markers, remained generally stable over one year of treatment.
Nine patients, or nearly one-third of participants, experienced side effects, but these were mild to moderate, and overall, the alternative dosing regimen was considered to be well tolerated.
Patients completing BRIGHT may enroll in its open-label extension study, designed to evaluate the long-term safety, tolerability, and efficacy of the less frequent dosing regimen. In it, participants will receive the treatment for up to seven years. The study is set to end in 2026.
“Together with Chiesi, we remain committed to meeting the needs of people with Fabry disease and bringing additional therapeutic options to market,” Bashan said.
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