FDA Breaks New Ground With Transplant Drug Approval

Tacrolimus (Prograf) won FDA approval late Friday to prevent lung transplant rejection, a newsworthy development on two counts.

In addition to the immunosuppressant becoming the first to be OK’d for that indication, the decision is also the most tangible demonstration so far of the agency’s new openness to “real-world evidence” as the basis for drug approvals.

No prospective trial was conducted with tacrolimus in lung transplant patients. Instead, the primary evidence for the drug’s effectiveness in this setting came from the federal government’s transplant registry, along with Social Security mortality records. These data showed “dramatic improvement in outcomes” with tacrolimus “compared to the well-documented natural history of a transplanted [organ] with no or minimal immunosuppressive therapy,” the FDA said in announcing the decision.

“This approval reflects how a well-designed, non-interventional study relying on fit-for-purpose real-world data, when compared with a suitable control, can be considered adequate and well-controlled under FDA regulations,” the agency said.

Prospective trial data in other indications — tacrolimus is already approved for preventing allograft rejection in liver, kidney, pancreas, bowel, and heart transplantation — supported the new approval, the FDA added. It also noted that the drug was already in routine use off-label to prevent lung transplant rejection.

The FDA first signaled its intention to use evidence from retrospective clinical usage to underpin formal drug and device approvals in 2016, with a New England Journal of Medicine article authored by a dozen senior officials. That led to a guidance document issued in 2019 laying out a pathway for drug sponsors to follow. (A similar document covering medical devices came out in 2017.)

Astellas Pharma, maker of Prograf, made the pitch for tacrolimus in lung transplantation. The drug is also available under other names from several generic manufacturers, but the FDA specified that only Astellas’s version is approved for this indication.