A drug developed by partners Protalix BioTherapeutics and Chiesi Group has won FDA approval, a regulatory decision that follows the product’s European approval last week, introducing new competition for the treatment of a rare disorder with few therapeutic options.
The FDA approval covers the treatment of adults who have Fabry disease, a rare inherited enzyme deficiency. The drug, known in development as pegunigalsidase alfa, will be commercialized in the U.S. under the brand name Elfabrio.
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In Fabry disease, a genetic mutation leads to insufficient levels of alpha galactosidase, an enzyme needed to break down a fatty substance called globotriaosylceramide (Gb3). The enzyme deficiency leads to the accumulation of Gb3 in tissues throughout the body, leading to pain, organ damage, and organ failure.
Standard treatment for Fabry disease is enzyme replacement therapy. Sanofi’s Fabrazyme, an engineered version of alpha galactosidase, has been available in Europe since 2001 and in the U.S. since 2003. Replagal, marketed by Takeda Pharmaceutical, has been available in Europe since 2001. It is not approved in the U.S. Both Fabrazyme and Replagal are administered as infusions every other week.
The 2018 FDA approval of Galafold from Amicus Therapeutics introduced another therapeutic option for Fabry. Rather than replacing the deficient enzyme, Galafold is designed to increase the activity of the alpha galactosidase that a patient already has. The capsule, taken once every other day, is intended for Fabry patients with a certain genetic mutation.
Elfabrio is an engineered version of alpha galactosidase administered as an infusion every two weeks. This enzyme replacement therapy is designed to offer a long half-life, but the clinical data so far have not established that Elfabrio’s half-life gives it a safety or efficacy edge. Protalix and Chiesi initially sought accelerated FDA approval for Elfabrio in 2020. In 2021, the agency rejected the drug, citing the need to inspect the drug’s manufacturing facility. No safety or efficacy issues were raised, but travel restrictions in 2021 due to the Covid-19 pandemic hindered the FDA’s ability to inspect the manufacturing sites of Elfabrio and many other drugs.
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The timing of the rejection letter threw another obstacle in Elfabrio’s path. The FDA noted that the accelerated approval of Sanofi’s Fabrazyme had recently been converted to full regulatory approval. That meant that any resubmission of an application for Elfabrio would need to address the Sanofi product.
The resubmission of Elfabrio last fall was based on clinical data from more than 140 patients, both those who have previously received enzyme replacement therapy and those who have not. The application included results from a head-to-head study against Fabrazyme showing Elfabrio met the main goal of demonstrating that it was comparable to the Sanofi product in controlling decline as measured by estimated glomerular filtration rate, an assessment of kidney function.
The most common adverse effects reported in Elfabrio’s clinical trials included infusion-associated reactions, cold symptoms, headache, diarrhea, fatigue, and nausea. The drug’s label carries a black box warning that flags the risk of hypersensitivity reactions including anaphylaxis. Clinical trial results showed that 20 (14%) of Elfabrio-treated patients experienced anaphylaxis.
“While much progress has been made in the treatment of Fabry disease, there is still a need for new treatment options,” Giacomo Chiesi, head of Chiesi Global Rare Diseases, said in a prepared statement. “We established Chiesi Global Rare Diseases to deliver innovative therapies and solutions for people affected by rare diseases. With the FDA approval of Elfabrio, we can now offer people living with Fabry disease an alternative treatment option.”
Chiesi and Protalix have not said when they plan to launch Elfabrio, nor have they disclosed a price for the drug. They will be going up against Fabry therapies well established in the market. Sanofi’s Fabrazyme generated €938 million in sales in 2022, an 11% increase over prior year sales. But its patents have expired and biosimilar versions pose competition in some parts of the world. For the fiscal year ended March 31, 2022, Takeda reported 51.7 billion Japanese yen (about $384.6 million) in revenue from Replagal. That figure was flat compared to the prior fiscal year. Amicus reported $329 million in Galafold sales for 2022.
Photo: Waldemarus, Getty Images
