EU agency urges against monthly dosing plan for Fabry drug Elfabrio
Enzyme replacement therapy remains authorized at lower dose every 2 weeks
The European Medicines Agency (EMA) has issued a negative opinion on a request to approve a less frequent and higher-dose regimen of Elfabrio (pegunigalsidase alfa), an approved enzyme replacement therapy (ERT) for adults with Fabry disease.
The request, submitted by Elfabrio’s developers, Chiesi Global Rare Diseases and Protalix Biotherapeutics, was accepted for review by the EMA at the end of last year. It sought approval for dosing once every four weeks at 2 mg/kg, in addition to the currently approved every-other-week dosing at 1 mg/kg.
The submission was supported by positive results from the Phase 3 BRIGHT clinical trial (NCT03180840) and its ongoing open-label extension study (NCT03614234), which evaluated Elfabrio’s safety and efficacy in patients transitioning to the proposed modified dosing schedule. Further support was provided by new pharmacological models and exposure-response analyses integrating data from prior studies.
The EMA, however, has deemed the available results insufficient to conclude on comparable efficacy between the two regimens.
“We are disappointed by the result of this review but want to express our immense appreciation for the collaboration of the patient community, researchers, and European Commission throughout this process,” Giacomo Chiesi, executive vice president at Chiesi Global Rare Diseases, said in a press release. “We are proud to be a part of this community and will continue to prioritize the potential to advance and evolve safe and effective solutions for Fabry disease with reduced treatment burden.”
Treatment approved in EU at lower dose every 2 weeks
Caused by a faulty or missing alpha-galactosidase A (alpha-Gal A) enzyme, Fabry leads to the buildup of fatty molecules, mainly globotriaosylceramide (Gb3), within cells. This progressively damages the kidneys, heart, and nervous system, ultimately driving Fabry disease symptoms.
Enzyme replacement therapy, or ERT, has been used for more than two decades as the mainstay approach for Fabry treatment. It delivers a functional alpha-Gal A enzyme through regular infusions into the bloodstream, temporarily restoring the body’s ability to break down Gb3 and helping to slow disease progression.
Elfabrio, an ERT approved for Fabry, was designed to increase enzyme stability in the bloodstream so that the therapy can remain active for a longer period compared with earlier treatments, helping to reduce treatment burden for patients. The treatment is administered as an intravenous, or into-the-vein, infusion every two weeks at a dose of 1 mg/kg.
The one-year BRIGHT study, which involved 30 people with Fabry who had previously been on other ERTs, evaluated whether a less frequent but higher dose of Elfabrio could be safely used in patients with stable disease.
We … remain committed to reducing the treatment burden for patients with Fabry disease. The results of this review do not change this priority.
Results showed that Elfabrio, given once every four weeks at 2 mg/kg, was generally safe and effective, maintaining effective levels in the bloodstream throughout the four-week interval.
While nearly one-third of participants experienced side effects, these were mostly mild to moderate in severity, and the alternative dosing regimen was considered to be well-tolerated overall.
Despite the EMA’s negative opinion on the proposed regimen, Chiesi and Protalix said they intend to continue working together to support the Fabry community and to pursue options that may further reduce treatment burden for patients.
Elfabrio remains approved in the European Union at the currently authorized dose of 1 mg/kg every two weeks.
“We, together with Chiesi, remain committed to reducing the treatment burden for patients with Fabry disease,” said Dror Bashan, Protalix’s president and CEO. “The results of this review do not change this priority. We are grateful to all of the patients and investigators, and their staff members, who participated in the [every-4-weeks] clinical trial programs.”
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