With these infections being problematic, a newer antiviral offers an alternative option for these patients.
Transplantation patients can be challenging to treat, especially with the introduction of a new organ or living tissue into the body and dealing with all the potential side effects including infections. For example, the development of cytomegalovirus (CMV) in post-transplant patients can bring about a whole host of issues.
“Once [clinicians] do identify that there's an infection, and are actively treating, seeing the CMV management oftentimes has to be balanced along with the risk of rejection,” said Daniele K. Gelone, PharmD, US Region Strategic medical lead- senior medical director Rare Disease/Transplant, Takeda. “There's a tug of war that clinicians are faced with that can be a challenge. And then there's the medications themselves—antiviral therapies. The tolerability profiles of antiviral therapy sometimes have side effect profiles that have an additive effect to some of the clinical presentation that's ongoing with CMV. And that could pose a challenge as well as resistance that could develop and all those items could lead to either inadequately treated or sub-optimally treated CMV.”
There is a newer antiviral, Takeda’s Livtencity (maribavir), available for post-transplant patients with CMV. The FDA approved the therapy in November 2021, and it was the first treatment indicated for adults and pediatric patients (12 years of age and older and weighing at least 35 kilograms) with post-transplant 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 at the time of the approval. “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.”
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:
Gelone sat down to speak with Contagion at the recent IDWeek conference about some of the challenges of CMV in this patient population and insights about maribavir as a treatment option.
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.