The US Food and Drug Administration (FDA) issued a complete response letter for the drug candidate, pegunigalsidase alfa, late last month. Later, Protalix said the rejection stemmed from the FDA’s pandemic-related inability to visit the manufacturing facility in Carmiel, Israel where it makes the enzyme replacement therapy using its plant cell-based protein expression system.
An inability to perform an inspection or facility assessment because of COVID-19 forced the FDA to delay 48 decisions on human drug applications over the first year of the pandemic. The FDA now has a roadmap for working through its backlog of inspections but its in-person assessments of foreign facilities are at the mercy of international travel restrictions.
Given the potential for the pandemic to continue to prevent FDA staff from visiting foreign facilities, Protalix plans to use an upcoming meeting with the agency to propose alternative approaches, as its CEO, Dror Bashan, explained on a May 14 quarterly results conference call with investors.
“It's possible to hold a virtual inspection,” Bashan said. “Maybe there is another alternative, like a record review inspection. We are not deciding for the FDA.. but we will raise all these alternatives again with [the] FDA and hopefully it will come to [an] agreed upon solution.”
The US drug regulator has already assessed the third-party European fill-and-finish facility for pegunigalsidase alfa using powers that enable it to request records from manufacturers. Bashan said Protalix is reviewing the agency’s comments with quality and regulatory consultants.
Assessment timeline
If the FDA wants to inspect the Carmiel site in person, it is unclear when the assessment will take place. Asked by an analyst for a timeline, Bashan said: “I wish I knew. We wish it will be sooner than later, but we do not control their timetable.”
The situation is complicated by a change in the regulatory situation for Fabry drugs. Recently, the FDA granted Sanofi’s Fabry treatment Fabrazyme full approval, 18 years after clearing it for use via its accelerated pathway.
“This new development will need to be addressed in the context of any potential resubmission seeking accelerated approval of PRX-102,” Bashan said.
Avrobio has already changed the development plan for its Fabry gene therapy in light of the change in the status of Fabrazyme on the grounds it “can no longer pursue an accelerated approval pathway for AVR-RD-01 with the FAB-GT trial as currently designed.”