"Cytomegalovirus (CMV) infection is worse than a simple viral infection in patients with solid organ transplant (SOT), but existing treatments have limitations. Reimbursement of new medicines is meaningful in terms of extending treatment options."

Livtencity (maribavir), which can be prescribed to post-transplant patients who have had limited treatment options, is receiving a favorable assessment. It can be used following initial treatment.

Livtencity, as a second-line treatment, was approved for reimbursement in April 2024 for patients who experienced an inadequate response to conventional antiviral agents or discontinued treatment due to serious adverse events.

Dr. Sang-Oh Lee, a professor at Seoul Asan Medical Center's Department of Infectious Diseases, who has the latest expertise in related fileds, emphasized that reimbursement approval of Livtencity elevated the flexibility of treatment strategy.

"Introduction of second-line treatment for CMV is receiving favorable assessment"

Cytomegalovirus (CMV) is a virus for which approximately 95% of Korean adults already possess antibodies. While it typically causes almost no symptoms in individuals with normal immune systems, it can progress to a severe illness in post-transplant patients who must take immunosuppressants.

Dr. Lee explained, "About 60% of solid organ transplant patients in Korea experience CMV infection, and approximately 13.7% of these progress to severe CMV disease." Dr. Lee added, "CMV disease is divided into CMV syndrome associated with systemic viral activation and localized infections affecting specific organs, with gastrointestinal involvement accounting for about 75% of these cases."

According to Dr. Lee, the risk of CMV infection varies depending on the type of transplanted organ. The risk of CMV viremia is highest in lung transplant patients, at around 10%, followed by heart and liver transplant patients at approximately 7-8%, and kidney transplant patients at approximately 5%.

Dr. Lee said, "When CMV DNA levels in a patient's blood rise above a certain threshold, even without symptoms, preemptive treatment is initiated. However, treatment sustainability often declined due to side effects of existing treatments, such as myelosuppression or nephrotoxicity."

Existing CMV treatments like ganciclovir and valganciclovir, despite their potent antiviral effects, caused adverse reactions such as myelosuppression, posing clinical limitations for immunocompromised transplant patients.

Furthermore, patients showing resistance or are refractory to these drugs had to use foscarnet or cidofovir, but these agents were limited in use due to severe nephrotoxicity concerns.

Livtencity is a novel drug that emerged to overcome the limitations of existing treatments. As an antiviral agent with a novel mechanism that targets the UL97 protein kinase, it has a lower burden of myelosuppression and nephrotoxicity compared to existing therapies. Its oral administration significantly improved patient convenience and treatment sustainability.

Dr. Lee stated, "Livtencity demonstrated superior efficacy in clinical studies in patient groups who developed resistance or refractoriness to previous treatments," and added, "Since its reimbursement approval last year, favorable responses have continued to be reported in clinical practice."

Dr. Lee has directly prescribed Livtencity to about 10 patients since its introduction, observing substantial treatment effects, including a stable decrease in CMV DNA levels in most treated patients.

Asan Medical Center in Seoul performs approximately 500 liver transplants and numerous lung transplants annually. The number of CMV disease cases among these patients is estimated to be around 40 per year. Livtencity is particularly regarded for demonstrating outstanding efficacy in various clinical situations, including liver and lung transplant patients, such as CMV hepatitis and chronic graft-versus-host disease (GVHD).

"The efficacy of Livtencity treatment is adequate, but reimbursement criteria need to be improved"

Notably, Dr. Lee particularly gave high marks for Livtencity's safety and treatment sustainability observed in clinical practice.

Dr. Lee said, "Livtencity has a superior safety profile compared to existing antiviral drugs, showing high patient satisfaction in terms of treatment sustainability in clinical settings. Since its use, there have been no cases of severe adverse reactions warranting treatment discontinuation, and its treatment sustainability is overwhelmingly superior to existing drugs."

However, Dr. Lee proposed that the current reimbursement criteria for Livtencity in Korea may need some improvement.

Currently, Livtencity's reimbursement criteria are set for cases where 'treatment has failed after using existing antiviral drugs (ganciclovir, valganciclovir) for at least 2 weeks, or severe side effects have occurred, or resistance has been confirmed.'

Dr. Lee views that while the current criteria are reasonable to a certain degree, they can be improved for actual clinical practice, as the reimbursement criteria are limited to solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patient populations.

Dr. Lee emphasized, "Currently, Livtencity's reimbursement criteria are limited to cases where refractoriness is confirmed after at least 2 weeks of treatment with existing therapies," and added, "This is a somewhat long period for high-risk patients, and since CMV can be worsened in a short time, more flexible and rapid reimbursement application criteria are needed."

Additionally, for transplant patients, Dr. Lee proposed that institutional improvements are necessary to extend reimbursement coverage to other severely immunocompromised patient groups, such as those with hematologic cancers, where CMV treatment is urgently needed.

Finally, Dr. Lee concluded, "The introduction of Livtencity has brought a substantial change to the CMV infection treatment environment in Korea. However, more improvement of related systems and policies is essential so that even more flexible and patient-customized approaches are available in the future."