Feb 23, 2021

The U.S. Food and Drug Administration (FDA) has partially rescinded a pair of supplemental Biologics License Applications (BLAs) the agency had granted, in error, for two recombinant factor IX products, BeneFIX® (Pfizer) and IXINITY (Aptevo). The supplemental BLAs in question were both approved by the FDA in 2020 and represented additional indications that ultimately ran against exclusivity rights of another product.   

Background:
On June 26, 2020, the FDA approved a supplemental BLA that granted  Benefix®  an indication for routine prophylaxis to reduce the frequency of bleeding episodes in adults and children with hemophilia B. On September 25, 2020, the indication for IXINITY was expanded to include routine prophylaxis to reduce the frequency of bleeding episodes in adults and adolescents 12 years of age or older with hemophilia B – the initial indication was for the control and prevention of bleeding episodes and for perioperative management in adults only.

The partial rescissions became necessary when during a review of agency records, the FDA determined that another product already had Orphan Drug exclusivity that precluded approval of the added indications that were specific to prophylaxis in adolescents and children. That product, Baxalta US Inc’s recombinant FIX therapy RIXUBIS – indicated for adults and children with hemophilia B for control and prevention of bleeding episodes, perioperative management, and routine prophylaxis – had been granted Orphan Drug status by the FDA several years prior.

It should be noted that Benefix® continues to be indicated for adults and children with hemophilia B for on-demand treatment and control of bleeding episodes and perioperative management of bleeding. It also retains its added indication for routine prophylaxis in adults. IXINITY also maintains its initial indications, plus its added indication for routine prophylaxis in adults.

In letters sent by the FDA to both Pfizer and Aptevo, the agency explains that the Orphan Drug provision allows for, among other things, seven years of exclusivity that “blocks approval of another applicant’s application for the same drug for the same indication.” Exclusivity for RIXUBIS remains in effect until September 12, 2021.

The FDA notified Pfizer and Aptevo that product labeling for BeneFIX® and IXINITY needs to be revised accordingly to reflect the modified indications, the exact language, and requisite instructions for which were included in the agency’s February 17th letters to both companies. The agency has made these letters available on their website:

February 17, 2021 Partial Rescission of Approval Benefix
February 17, 2021 Partial Rescission of Approval XINITY