FDA's antimicrobial adcomm unanimously backs Takeda's drug for post-transplant cytomegalovirus
The FDA’s antimicrobial drugs advisory committee on Thursday voted unanimously in favor of FDA approving Takeda’s antiviral for post-transplant cytomegalovirus.
The adcomm voted 17-0 on the question of whether the overall benefit-risk profile is favorable for the use of Takeda’s maribavir for the treatment of transplant recipients with CMV infection and disease refractory to treatment and with genotypic resistance to four other antivirals — ganciclovir, valganciclovir, foscarnet or cidofovir.
On whether the drug, which took about two decades to develop, should be approved for the same population but those without genotypic resistance to the four antivirals, the committee voted 17-0.
FDA’s briefing documents released ahead of the meeting showed how maribavir proved safe across multiple studies and statistically superior to investigator-assigned treatment (IAT) in a Phase III trial, which Takeda announced earlier this year.
While several members of the adcomm said during the discussion that they don’t want to let perfect be the enemy of the good in terms of the data around maribavir, several others questioned the endpoint used in that trial, and why the trial didn’t include a more diverse population.
Adcomm chair Lindsey Baden of the Dana-Farber Cancer Institute, who voted in favor of the approval, also called the data “messy,” but said the totality of data is persuasive. He also noted the advantages of an oral drug in this indication.
Committee member Nancy Bridges, chief of the transplantation branch at the NIH’s National Institute of Allergy and Infectious Diseases, who voted in favor of approval also said that overall, “the data are very persuasive.”
But she noted that the participants in the Phase III trial “were overwhelmingly white,” even though this condition has a higher prevalence among African Americans. “I’d like to see some data from the company on efficacy in African Americans, which we don’t have,” Bridges said.
George Siberry, a medical officer at the US Agency for International Development, also said it was disappointing that no adolescents were included in the pivotal trial.
Peter Weina, director of the Defense Health Agency, said that even if the drug is approved for a narrow population, it’ll be used for all different indications off-label.
“I’m torn that the difference between genotypic resistance and no genotypic resistance is truly a moot point here,” Weina said.
An approval from FDA would cap a long and rocky history for the drug, which has changed hands several times over the last two decades following both positive and negative trials.
GlaxoSmithKline first synthesized the drug about 20 years ago and did some early clinical work before licensing it to the rare disease and infectious disease-focused biotech ViroPharma.
ViroPharma then missed a primary endpoint in a Phase III study in 2009. Maribavir failed to prevent CMV infections better than placebo in patients receiving bone marrow transplants. ViroPharma suggested a higher dose might lead to a better response, but ended up passing the candidate to Shire as part of a $4.2 billion buyout in 2013.
Shire upped the dose in various pharmacokinetic and efficacy studies, and in 2016, a Phase II study showed that the drug helped clear infections. The FDA commended the results with a breakthrough designation in 2018. And the following year, Takeda completed its acquisition of Shire for $62 billion.