Chiesi’s flagship Fabry drug heads for FDA verdict in early 2021

The FDA has started its review of Israeli biotech Protalix BioTherapeutics and partner Chiesi’s Fabry disease therapy pegunigalsidase alfa, setting up a possible approval by 27 January.

The enzyme replacement therapy (ERT) – also known as PRX-102 – has been granted a priority review by the US regulator, and is the top prospect in Chiesi’s recently formed rare diseases division.

Fabry disease is a rare genetic disease caused by a deficiency of an enzyme called alpha-galactosidase A that causes a build-up of toxic metabolites that cause a range of symptoms including pain, gastrointestinal symptoms and kidney damage.

Like other ERTs, pegunigalsidase alfa is given via an intravenous infusion and works to replenish the levels of alpha-galactosidase A, but has been modified to stabilise the enzyme and may allow less frequent dosing.

If approved, pegunigalsidase alfa will compete with established ERT drugs like Sanofi Genzyme’s Fabrazyme (agalsidase beta) and Takeda’s Replagal (agalsidase alfa), as well as Amicus Therapeutics’ newer, orally-active drug Galafold (migalastat) which made its debut in 2018 and is designed to bind and stabilise the enzyme in the body.

Earlier this year, Protalix and Chiesi reported results from the phase 3 BRIDGE trial showing that a year’s treatment with pegunigalsidase alfa was well-tolerated and seemed to slow kidney disease progression more effectively than Replagal, whilst also reducing biomarkers of Fabry disease.

The trial wasn’t a head-to-head comparison of the two drugs, but charted the course of treatment with the new drug in Fabry patients who had previously been maintained on Replagal therapy.

The initial application with the FDA is for dosing of 1mg/kg pegunigalsidase alfa every two weeks, the same interval as Fabrazyme and Replagal.

In the meantime, Chiesi and Protalix are also conducting a phase 3 trial – called BRIGHT – to see if the efficacy of their drug is retained at a dose of 2mg/kg given every four weeks.

Market research firm Optima Insights has predicted that sales of Fabry disease drugs will more than double from around $1.8 billion last year to $3.8 billion by 2027, driven by new oral drugs such as Galafold as well as gene therapies that are still in clinical development.

It says ERTs will remain a key part of Fabry treatment, although the first generation drugs could start to see biosimilar competition in the intervening period.