UPDATED: Takeda succeeds where other pharmas have failed with PhIII win for cytomegalovirus castoff maribavir
Maribavir, once a trial dud and multiple-time castoff, received new life from the FDA right before Takeda picked up Shire in 2019. Now, Takeda is posting winning late-stage data from the drug that could help it succeed where so many others have failed.
In a 352-person trial comparing maribavir to physician’s choice antivirals, more than twice as many patients on maribavir achieved CMV viremia clearance at eight weeks — the study’s primary endpoint, according to Takeda. Of the 235 patients who received maribavir, 131 (or 55.7%) achieved clearance versus 28 of 117 (or 23.9%) of those on conventional antiviral therapies (p<0.001). Viremia is the isolation of CMV by culture.
CMV, or cytomegalovirus, is a common virus that affects much of the population without causing symptoms, but it can be dangerous to people with compromised immune systems, including recipients of bone marrow or organ transplants.
Volunteers in Takeda’s open-label trial, dubbed SOLSTICE, randomly received either maribavir, or one or a combination of commonly used antiviral therapies like ganciclovir, valganciclovir, foscarnet or cidofovir. The participants, who were hematopoietic cell transplant and solid organ transplant recipients, were treated for eight weeks, then followed for another 12.
Breaking it down further, Takeda said 55.6% of solid organ transplant patients on maribavir saw CMV viremia clearance at week eight, compared with 26.1% of those on other therapies. And of the hematopoietic cell transplant patients, 55.9% achieved clearance at week eight compared to 20.8% on other drugs.
In addition to the primary endpoint, Takeda says it met a key secondary endpoint: improvement in the clearance of CMV viremia and associated symptom control through four months And those who took maribavir showed a lower incidence of treatment-related toxicities common with other antivirals, according to the company.
Treatment-related serious adverse events led to the deaths of one patient in each treatment group, according to Takeda, though it’s unclear what caused the deaths. As of press time, the company declined to provide more information.
Takeda offered a first glimpse at the Phase III results back in December, and announced that it would take the data to regulators in the US and Europe. In an emailed statement, Takeda said it plans to file with the FDA in the first half of FY 2021.
An approval would be a sweet end to maribavir’s wild-two-decade ride. GlaxoSmithKline first synthesized the drug 20 years ago and did some early clinical work, before licensing it to the rare disease and infectious disease-focused biotech ViroPharma.
ViroPharma successfully took it through Phase II, then missed the 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 during a $4.2 billion buyout in 2013.
Shire ran with ViroPharma’s idea, giving 4 to 12 times more drug in various pharmacokinetic and efficacy studies. They got the results they were looking for in 2016, proving in a Phase II study that 400mg, 800mg, and 1200mg helped clear infection. The FDA commended the results with a breakthrough designation in 2018. And the following year, Takeda completed its acquisition of Shire for $62 billion.
Maribavir has come a long way indeed, but it’s not over the goal line just yet.