Takeda’s cytomegalovirus (CMV) drug, maribavir, beat 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.
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.
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. After six weeks, 79% of maribavir patients had cleared the virus, compared to 67% of Valcyte patients. The findings appear in the New England Journal of Medicine.
“The Phase 2 study showed that maribavir has demonstrated antiviral activity as a potential treatment of CMV infection and demonstrated a reduction of actively multiplying CMV in the blood, following hematopoietic cell transplant or solid organ transplant,” Takeda said in a statement.
Takeda is already enrolling two phase 3 studies for maribavir. One will test the drug in stem cell transplant patients with their first CMV infection and the other will test it in patients who have received a stem cell or solid organ transplant and have a resistant or refractory CMBV infection. The second study will pit maribavir against treatments chosen by the study investigators, including Valcyte and a trio of antivirals that were approved in the 1980s and 1990s.
Maribavir’s safety profile may pose a challenge—67% 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.
“There is a significant unmet need for additional treatment for post-transplant patients with CMV infection especially those with a CMV infection that is resistant to currently available antiviral therapies,” said principal investigator Johan Maertens, M.D., Ph.D. of Universitaire Ziekenhuizen Leuven in Leuven, in a statement. “These results are encouraging and warrant further investigation of maribavir as a potentially effective and tolerated treatment for CMV in transplant patients.”
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 the hereditary angioedema drug Cinryze in 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.