Protalix and Chiesi Plan Q1 2020 Filing For Accelerated FDA Approval
Executive Summary
The companies plan to use surrogate endpoint data to win approval to challenge Sanofi and Shire for the Fabry disease market.
Protalix BioTherapeutics Inc. and Chiesi Farmaceutici SPA plan to file for accelerated approval of Fabry disease drug pegunigalsidase alfa in the first quarter of next year after talks with US Food and Drug Administration found a surrogate path forward.
The partners are testing the drug, also known as PRX-102, in three Phase III trials to establish it as a rival to Sanofi’s Fabrazyme and Shire PLC’s Replagal in the treatment of the rare genetic disease. Those trials will read out over the next two years, which would put Protalix and Chiesi on track to win approval in the US via the conventional pathway in the second half of 2021.
As PRX-102 has FDA fast-track status, it is eligible for a priority, six-month review, rather than the usual 10-month assessment process.
Analysts at Jefferies think PRX-102 could generate peak global sales of $250m (€222m) and assign it a 60% probability of success. Full-year sales of Sanofi’s Fabrazyme totaled €755m in 2018, up 10% on the previous year. Replagal generated revenues of €490m for Shire and its new owner Takeda Pharmaceutical Co. Ltd..
Protalix and Chiesi brought forward plans to file for approval to challenge Fabrazyme and Replagal after talking to the FDA about surrogate endpoints. Protalix left their first meeting with the FDA feeling “cautiously optimistic” about the potential to use the pathway.
At a second meeting, Protalix and Chiesi talked the FDA through the kidney and estimated glomerular filtration rate data they have generated in the clinic to date and the substance of their planned filing for accelerated approval. The preliminary data suggest switching patients from Replagal to PRX-102 may improve kidney function.
The FDA’s response encouraged Protalix and Chiesi to start preparing to file for approval on the basis of Phase I/II data and results from one of the ongoing Phase III trials. If the FDA authorizes PRX-102, Protalix and Chiesi could later use final data from the wider Phase III program to confirm the clinical benefit of the the drug.
Financial Boon?
Accelerating the regulatory process may improve Protalix’s financial position. Protalix thinks the $30m it had in cash at the end of March will see it through to the middle of next year, around the time that the FDA could authorize PRX-102. Chiesi will make a payment to Protalix when the drug is approved under the terms of a 2018 licensing agreement, which features $760m in milestones.
Talking to investors earlier this year, Protalix CFO Yossi Maimon called the approval-based milestone “significant,” adding that an accelerated authorization “could cascade a lot of potential milestones and payments et cetera that could change the picture very quickly.”
The picture for Protalix has been troubled at times. Protalix won approval for a Pfizer-partnered drug to treat Gaucher disease in 2012. However, the drug, which uses the same plant-based expression system as PRX-102, struggled to win market share from rival products sold by Sanofi and Shire. Protalix sold the rights to the drug outside of Brazil to Pfizer for $36m in cash in 2015.
Striking the deal with Pfizer gave Protalix money to advance PRX-102, the centerpiece of its then-new strategy to develop “clinically superior biologics.” In the case of PRX-102, Protalix sought to improve on the half-life of Fabrazyme and Replagal by using covalent cross-linking to generate a stable dimer. Pharmacokinetic studies show PRX-102 has a half-life of around 80 hours, compared to two hours or less for Fabrazyme and Replagal.
The extended half life could translate into a less onerous dosing schedule. One of the three Phase III trials is administering PRX-102 every four weeks. Replagal and Fabrazyme are dosed every two weeks via infusions that take 40 minutes and upward of 90 minutes, respectively.
Interim data from the assessment of the once-monthly regimen of PRX-102 are due in the second half of 2019, with final results to follow early the following year. Final data from the Phase III that will support accelerated approval are due before the end of 2019.