Chiesi, Protalix’s Fabry disease treatment is approved as Elfabrio joins Fabrazyme, Galafold

The FDA has greenlit an enzyme replacement therapy for adults with a rare, inherited disease in which abnormal deposits of fatty substances build up and cause pain and sometimes end-organ failure — two years after a CRL and just days after Europe approved the therapy.

The approval for Chiesi Global Rare Diseases and Protalix BioTherapeutics’ Elfabrio puts the treatment in the same arena as Sanofi’s Fabrazyme and Amicus Therapeutics’ Galafold in treating Fabry disease. Sanofi’s therapy was given an accelerated approval in the early aughts, but a full approval didn’t come until 2021. Amicus also originally received an FDA rejection, though it wound up securing a nod in 2018.

Dror Bashan

“This approval is a testament to the dedication of the Protalix and Chiesi teams to deliver this much needed new therapeutic option to patients in need,” Protalix president and CEO Dror Bashan said in a press release. “The totality of clinical data suggests that Elfabrio has the potential to be a long-lasting therapy.”

In April 2021, Chiesi and Protalix announced the rejection, which the companies attributed to the FDA’s inability to inspect a manufacturing site in Israel. The agency says the inspection issue alone wasn’t the only reason for the CRL.

The biotechs would go on to resubmit their biologics license application for pegunigalsidase alfa, known also as PRX-102, in November of last year. Takeda’s Replagal has been approved in Europe and Japan for years, but never made it to approval in the US, despite filling a Fabrazyme shortage for a period.

At a time when other biotechs in the field are adjusting trials and going through pipeline reorgs, Chiesi and Protalix will bring to market their therapy, which is a recombinant human α–Galactosidase–A enzyme that they say is meant to have a long half-life, initially at 78.9 ± 10.3 hours.

The landscape of investigational therapies also includes products developed by 4D Molecular Therapeutics, Sangamo Therapeutics and CANbridge Pharmaceuticals, among others. The list at one point included Freeline Therapeutics, which flashed a red light on its gene therapy last month; Avrobio, which axed its candidate about 18 months ago; and Idorsia, which failed a Phase III in fall 2021. 4DMT is working on getting its gene therapy clinical hold lifted.

Elfabrio was tested in more than 140 patients, some of whom were followed for up to seven and a half years. In a study investigating it directly against Fabrazyme injection, Elfabrio met its primary endpoint. Its efficacy was non-inferior to the standard drug and was “generally well-tolerated,” the companies said.

Giacomo Chiesi

“While much progress has been made in the treatment of Fabry disease, there is still a need for new treatment options,” said Giacomo Chiesi, head of Chiesi Global Rare Diseases, in a statement.

On the warning label, FDA says cardiopulmonary resuscitation equipment should be “readily available” as patients given the therapy have experienced anaphylaxis, or an allergic reaction. Four, or 3% of treated patients in clinical trials, experienced those allergic reactions within five to 40 minutes of the initial infusion start.

About one in 40,000 to 60,000 people have the enzyme deficiency, the companies said.

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