FDA Greenlights Maribavir for Select Post-Transplant Recipients With CMV

FDA

The FDA has approved maribavir (Livtencity) for the treatment of adult and pediatric patients aged 12 years and older weighing at least 35 kg who have post-transplant cytomegalovirus (CMV) infection that does not respond to available antiviral treatment.¹

The regulatory decision was based on findings from the pivotal phase 3 TAK-620-303 (SOLSTICE) trial (NCT02931539), which demonstrated that maribavir was superior to conventional antiviral therapies like ganciclovir (Zirgan), valganciclovir (Valcyte), foscarnet (Foscavir), or cidofovir (Vistide) alone or in combination in this patient population.²

Results showed that more than twice as many transplant recipients with relapsed/refractory CMV infection or disease who received maribavir (n = 131/235) achieved CMV viremia clearance at study week 8 vs those on conventional antiviral therapies (n = 28/117), at 55.7% and 23.9%, respectively (95% CI, 32.8%; 22.8%-42.7%; P < .001). Moreover, the benefit with maribavir over conventional antivirals was found to be maintained through study week 16.

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

The multicenter, open-label, active-controlled, phase 3 trial enrolled transplant recipients with CMV infection who were refractory with or without resistance to 1 or a combination of conventional treatment approaches.

First, participants underwent a 2-week screening period. Then, they were randomized 2:1 to receive either maribavir at a dose of 400 mg or investigator-assigned treatment (IAT) for 8 weeks. Once the treatment period was completed, patients had 12 weeks of follow-up.

The primary end point of the trial was the proportion of patients who achieved confirmed CMV viremia clearance, which was defined as plasma CMV DNA of less than 137 IU/mL in 2 consecutive tests at least 5 days apart at a central laboratory, vs IAT at the end of study week 8. A key secondary end point was demonstrating improvement with maribavir over conventional therapies in clearance of CMV viremia and associated symptom control maintained through study week 16.

Data from a subgroup analysis of the trial showed that maribavir lead to more than triple the amount of transplant recipients with confirmed genotypic-resistant CMV infection at baseline experiencing CMV viremia clearance at study week 8 compared with those who received conventional approaches, at 62.8% (n = 76/121) vs 20.3% (n = 14/69), respectively (95% CI, 44.1%; 31.3%-56.9%).³

Additionally, 55.6% of solid organ transplant recipients with relapsed/refractory CMV who received maribavir had confirmed CMV viremia clearance compared with 26.1% of those given conventional approaches. In hematopoietic cell transplant recipients with relapsed/refractory CMV infection, 55.9% and 20.8% of patients, respectively, achieved confirmed CMV viremia clearance.

Notably, more recipients who received maribavir were noted to have CMV clearance at week 8, regardless of viral load category compared with those who received conventional approaches. Among the subset of patients with a low viral load category at baseline, defined as less than 9100 IU/mL, 62.1% of those who received maribavir experienced CMV clearance vs 24.7% of those who received conventional approaches; in those with intermediate or high viral load category at baseline, defined as 9100 IU/mL or more, these rates were 43.9% and 21.9%, respectively.

The most frequent adverse effects reported with maribavir include taste disturbance, nausea, diarrhea, vomiting, and fatigue.

Maribavir could reduce the antiviral activity of ganciclovir and valganciclovir, according to the FDA; as such, coadministration of these agents is not recommended. Moreover, virologic failure because of resistance can occur during, and after, treatment with maribavir. As such, the regulatory agency stated that the CMV DNA levels should be monitored and resistance to the agent should be checked if the patient is unresponsive to treatment or they relapse.

References

1. FDA approves first treatment for common type of post-transplant infection that is resistant to other drugs. News release. FDA; November 23, 2021. Accessed November 24, 2021. https://bit.ly/3FMaI5q
2. Takeda’s maribavir phase 3 clinical trial met primary endpoint of superiority to conventional antiviral therapy in transplant recipients with refractory, with or without resistance, cytomegalovirus infection/disease. News release. Takeda Pharmaceutical Company Limited. February 12, 2021. Accessed November 24, 2021. https://bit.ly/3oF9UYT
3. Subgroup analysis from phase 3 clinical trial supports efficacy of maribavir over conventional therapies in transplant recipients with cytomegalovirus infection (refractory, with or without resistance). News release. Takeda Pharmaceutical Company Limited. March 15, 2021. Accessed November 24, 2021. https://bit.ly/342BlT3