FDA Approves Maribavir for CMV Infections After Transplant

The Food and Drug Administration (FDA) announced today the approval of Takeda’s Livtencity (maribavir) as the first treatment for treating adults and pediatric patients (12 years of age and older and weighing at least 35 kilograms) with post-transplant cytomegalovirus (CMV) infection/disease that does not respond with or without genetic mutations that cause resistance) to available antiviral treatment for CMV.

“Transplant recipients are at a much greater risk for complications and death when faced with a cytomegalovirus infection,” John Farley, MD, MPH, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said. “Cytomegalovirus infections that are resistant or do not respond to available drugs are of even greater concern. Today’s approval helps meet a significant unmet medical need by providing a treatment option for this patient population.”

Maribavir works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication. The therapy is an orally bioavailable anti-CMV compound. It is currently the only antiviral drug for treating adult post-transplant patients with CMV in hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).

From a global perspective, there is an estimated 200,000 adult transplant recipients, and CMV is one of the most common viral infections, affecting 16-56% of SOT recipients and 30-70% of HSCT recipients.

Data Findings

The TAK-620-303 (SOLSTICE) trial was a multicenter, randomized, open-label, active-controlled trial comparing 8 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), according to Takeda.

The 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. In addition, the SOLSTICE trial met 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.

More than twice (55.6%, 79/142) as many SOT recipients with R/R CMV infection at baseline treated with maribavir achieved confirmed CMV viremia clearance at study week 8 (end of treatment phase) compared to those treated with conventional antiviral therapies (26.1%, 18/69) (investigator assigned treatment; IAT consists of one or a combination of ganciclovir, valganciclovir, foscarnet or cidofovir) (adjusted difference [95% CI]: 30.5% [17.3, 43.6]).¹ The results presented showed consistent efficacy in SOT recipients receiving maribavir in heart, lung and kidney transplants.

Key findings included:

• More than 3 times as many lung transplant recipients with R/R CMV infection treated with maribavir achieved confirmed CMV viremia clearance as compared to those on conventional therapies (47.5% [19/40] vs 13.6% [3/22]; adjusted difference [95% CI]: 38.2% [16.89, 59.53]).
• More than 1.5 times as many kidney transplant recipients with R/R CMV infection treated with maribavir achieved confirmed CMV viremia clearance as compared to those on conventional therapies (59.5% [44/74] vs 34.4% [11/32]; adjusted difference [95% CI]: 26.7% [7.48, 45.85]).
• 42.9% (6/14) of heart transplant recipients with R/R CMV infection treated with maribavir achieved confirmed CMV viremia clearance as compared to 11.1% (1/9) of those on conventional therapies (adjusted difference [95% CI]: 30.7% [-1.72, 63.15]).

“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,” Obi Umeh, MD, vice president and Maribavir Global Program Leader, Takeda, said at the time of the data's release. "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.”

Reference

1. Avery R. Randomized Phase 3 Open-Label Study of Maribavir vs Investigator-Assigned Therapy for Refractory/Resistant Cytomegalovirus Infection in Transplant Recipients: Subgroup Analyses of Efficacy by Organ. In: American Transplant Congress (ATC) 2021 Virtual Connect; 2021.