Companies challenge EMA advice rejecting monthly Elfabrio dosing
Chiesi, Protalix argue data support less-frequent, higher-dose infusions
Chiesi Global Rare Diseases and Protalix Biotherapeutics are asking a committee of the European Medicines Agency (EMA) to reconsider its recent rejection of a monthly dosing plan for their approved treatment, Elfabrio (pegunigalsidase alfa), for Fabry disease. The proposed regimen would provide patients with a more convenient alternative to the current two-week infusion schedule.
“Both Chiesi and Protalix remain fully committed to working closely with the EMA through the re-examination process and to addressing the high unmet medical needs of the Fabry community,” the two companies stated in a press release. The companies did not specify when a decision on the re-examination is expected.
Fabry disease is a genetic disorder caused by mutations in the gene that encodes the alpha-galactosidase A (alpha-Gal A) enzyme, which is necessary for breaking down certain fatty molecules. In people with Fabry, these fatty molecules accumulate to toxic levels in cells, causing damage that ultimately drives disease symptoms, such as kidney problems.
How elfabrio works
Elfabrio is an enzyme replacement therapy designed to deliver a working version of the alpha-Gal A enzyme into the body, clearing out toxic fatty molecule buildups to slow disease progression. It is given by infusion into the bloodstream.
In the European Union, Elfabrio is currently approved for adults with Fabry disease at a dose of 1 mg/kg every two weeks. Late last year, Chiesi and Protalix submitted an application seeking approval of an alternative dosing schedule, where a dose twice as high is given half as frequently (2 mg/kg every four weeks).
The submission was primarily based on data from the Phase 3 BRIGHT clinical trial (NCT03180840) and its ongoing open-label extension study (NCT03614234), which evaluated the modified dosing schedule in 30 adults with Fabry disease. Results showed the less-frequent, higher-dose infusions were well tolerated overall, and kidney function remained stable. Additional pharmacological analyses from other studies also supported the companies’ application.
Last month, the EMA’s Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion recommending against approving the less-frequent regimen. It stated the available data were insufficient to conclude that the less-frequent dosing schedule is equally effective as the approved regimen.
In the EU, the CHMP is responsible for reviewing data on applications seeking approval of new medical treatments. Its recommendations are sent to the European Commission, which has final say over medication approvals in the EU. The commission is not required to abide by the committee’s recommendations, but it almost always follows them.
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