Takeda's maribavir hits phase 3 goal as pharma looks forward to regulatory talks

Takeda US facility
(Takeda)

Takeda’s experimental TAK-620 (maribavir) has hit its main phase 3 goal in helping transplant patients with refractory/resistant cytomegalovirus (CMV) infection.

Patients who have undergone a transplant are among the most vulnerable to CMV infection because they must take immunosuppressive drugs to ward off organ rejection.

CMV doesn’t usually cause symptoms in healthy people, but once someone is infected, the virus stays in their body in a dormant state. However, it can “wake up” in people with weakened immune systems, like transplant patients.

Takeda is hoping to join only a handful of other treatments for the disease, and its phase 3 data show it has hit its primary endpoint, taking it a step closer to a potential regulatory submission.

The data come out of an open-label, active-controlled trial comparing eight weeks of treatment with either maribavir or investigator-assigned treatment (IAT) in transplant recipients with CMV infection refractory or resistant to existing antiviral treatments (i.e., one or a combination of ganciclovir, valganciclovir, foscarnet or cidofovir).

Top-line data released Friday showed the so-called SOLSTICE trial met its primary endpoint, defined as the proportion of patients who achieved confirmed CMV viremia clearance compared to IAT at the end of study Week 8.

It also hit its key secondary endpoint, defined as achievement of CMV viremia clearance and symptom control at end of Week 8 and maintained through Week 16. “No new safety signals were identified and maribavir was associated with lower incidence of neutropenia compared to IAT,” the Japanese pharma said/

More detailed data will be published soon, it added.

“Achieving the primary endpoint of the SOLSTICE trial is an exciting new development in the search for a treatment for transplant recipients with refractory/resistant CMV infection,” said Obi Umeh, M.D., vice president and maribavir global program leader at Takeda.

“Today, transplant patients who do not respond or experience adverse events related to existing therapies may be at higher risk for complications from the virus, including transplant failure and death. Maribavir has the potential to redefine management of post-transplant CMV infections by helping patients clear the virus with less treatment limiting toxicities.

“We look forward to discussing these data with global health authorities including the U.S. Food and Drug Administration and European Medicines Agency as we work to bring maribavir to patients.”

Last fall, maribavir beat out Roche’s Valcyte at clearing the virus from patients’ blood in a phase 2 study. The study compared the drugs in patients with CMV infection after receiving an organ transplant or a stem cell transplant.

The phase 2, open-label study tested three doses of maribavir in 159 adults, comparing it to Valcyte (valganciclovir). After three weeks of treatment, 62% of patients taking maribavir had no signs of CMV in their blood plasma, compared to 56% of those on Valcyte.

There were, however, some safety worries: Sixty-seven percent of patients taking maribavir had a treatment-related side effect, compared to 22% of those on Valcyte. Serious side effects, such as acute graft-versus-host disease, diarrhea and renal failure, affected 10% of maribavir patients versus 2% of Valcyte patients. But the lack of treatments for patients with stubborn CMV infections may outweigh these issues. Maribavir has orphan drug status in the U.S. and EU.

Maribavir, also called TAK-620, has had a checkered past. ViroPharma abandoned a phase 3 CMV trial in 2009 after the drug failed to beat placebo in reducing the rate of CMV in patients who had undergone a bone marrow transplant. Maribavir, along with hereditary angioedema drug Cinryze, ended up at Shire through its $4.2 billion ViroPharma buyout in 2013 and eventually landed at Takeda following its $62 billion megamerger with Shire.