Takeda's Maribavir Outperforms Roche's Valcyte in Phase 2 CMV Trial

Compiled by Fan Dongdong

Recently, Takeda announced that its cytomegalovirus (CMV) drug maribavir outperformed Roche’s Valcyte in a Phase 2 study. The study compared the efficacy of maribavir in patients with CMV infection who had undergone organ or stem cell transplantation, and the results demonstrated that maribavir was more effective at clearing the virus from patients’ blood.

This Phase 2, open-label study evaluated three doses of maribavir in 159 adult patients and compared their efficacy with that of Valcyte. After three weeks of treatment, 62% of patients receiving maribavir achieved undetectable cytomegalovirus (CMV) DNA in plasma, compared with 56% of those treated with Valcyte. At six weeks, viral clearance was achieved in 79% of patients in the maribavir group versus 67% in the Valcyte group. The trial results have been published in The New England Journal of Medicine.

Maribavir, also known as TAK-620, was initially developed by ViroPharma. The company abandoned the drug's development in 2009 after a devastating failure in a clinical trial. In 2013, Shire acquired the drug for $4.2 billion, and following Takeda's acquisition of Shire in May 2018, the rights to the drug were transferred once again to Takeda.

Maribavir can precisely inhibit the UL97 protein kinase of cytomegalovirus, thereby blocking key processes in viral replication within patients, including viral DNA replication and gene expression. The drug has previously received orphan drug designation in both the United States and the European Union for the treatment of severe cytomegalovirus infections in high-risk patient populations (such as transplant recipients) and for cytomegalovirus infections in immunocompromised patients.

Currently, Takeda has initiated patient recruitment for two Phase 3 studies of maribavir. The first trial will evaluate the drug’s efficacy in stem cell transplant recipients experiencing cytomegalovirus (CMV) infection for the first time, as well as in patients who have undergone stem cell or solid organ transplantation and have resistant or refractory CMV infection. The second study will compare the therapeutic efficacy of maribavir with that of other agents, including Valcyte and three antiviral drugs.

However, safety concerns may pose a challenge to the drug’s successful market approval. The results showed that 67% of patients in the maribavir treatment group experienced treatment-related adverse events, compared to only 22% in the Valcyte treatment group. More serious adverse effects associated with the drug included acute graft-versus-host disease, diarrhea, and renal failure. Nevertheless, the current lack of therapeutic options for refractory cytomegalovirus infection in clinical practice may lead regulatory authorities to relax restrictions on the drug’s safety profile.

The drug’s future main competitors also include Merck & Co.’s Prevymis. Prevymis received approval from the U.S. FDA for market launch last November and was approved by UK regulators this May. In a pivotal Phase III clinical trial, the drug met its primary endpoint, with results showing that treatment with Prevymis significantly reduced the incidence of cytomegalovirus infection (38% vs. 61%).

Reference Source: Takeda’s CMV Drug Outshines Roche’s Valcyte in Phase 2