‘2nd line opt for CMV is limited…should improve access'

That has been shown to be effective in patients with resistance

Professor Sung Shin, Department of Kidney and Pancreas Transplantation, Asan Medical Center

CMV infection, which occurs in organ transplant patients, has limited options after developing resistance to existing therapies

Livtencity demonstrated efficacy and safety in clinical trials…” should be reimbursed to benefit more patients”

Sung Shin, Professor of Kidney and Pancreas Transplantation at Asan Medical Center (Director of General Affairs, the Korean Society for Transplantation)

An expert had suggested that we improve access to a new cytomegalovirus (CMV) treatment drug that has shown effect in patients with resistance as CMV has a major impact on transplanted organs.

 

Sung Shin, Professor of Kidney and Pancreas Transplantation at Asan Medical Center (Director of General Affairs, the Korean Society for Transplantation) expressed so at a meeting with Dailypharm, explaining how Livtencity, which has been shown to be effective in second-line treatment, could be beneficial amid the rising number of CMV patients developing resistance to existing first-line therapies.

 

CMV is a member of the herpesvirus family that causes infectious diseases.

 

The risk of CMV infection is particularly high after organ transplantation when the patient’s immunity is lowered.

 

CMV is a common complication in kidney transplant patients, to the extent that around half of the patients report infections.

 

If not treated in time, it can lead to a variety of complications, including pneumonia and lung inflammation, but treatment options are limited for patients who develop resistance to first-line therapy, raising the need for new second-line options.

 

Takeda's CMV therapy, Livtencity (maribavir), has demonstrated efficacy in patients who are resistant or intolerant to existing first-line therapies.

 

In clinical trials, Livtencity demonstrated more than double the CMV viremia clearance rate compared to existing treatment options and had lower toxicity.

 

Professor Shin welcomed the introduction of a new class of antivirals for resistant and treatment-refractory CMV and emphasized the need for its reimbursement to increase patient access to Livtencity CMV, predominantly affects organ transplant patients, and can potentially be fatal Delayed treatment of CMV can lead to the infection of various organs.

 

Especially in the early stages of transplantation, when immunity is low, it can lead to severe pneumonia, enteritis, sepsis, and even death.

 

CMV infection is known to be especially prevalent in kidney transplant patients.

 

More than 2,000 patients receive kidneys in Korea every year.

 

According to reports, more than 50% of them are infected with CMV, and more than 10% of the infected patients show infected symptoms.

 

As much as it is difficult to receive a kidney transplant, it is also important to manage various viruses after the transplant.

 

Professor Shin said, “CMV infection is associated with earlier loss of function in the transplanted kidneys compared to uninfected patients.

 

Also, CMV infection is associated with a significantly higher risk of fatal pneumonia and death from severe infections.” As such, early administration of effective antiviral therapy is important for organ transplant patients susceptible to infections.

 

However, with a reported 60% resistance rate to existing first-line antivirals such as ganciclovir and valganciclovir, only a limited range of second-line CMV treatment options exist due to toxicity issues.

 

MSD's Prevymis (letermovir) has emerged as a prophylactic therapy for CMV infection, but can only be used up to 100 days after organ transplantation.

 

Professor Shin explained, "The goal of CMV treatment is the achievement of complete negative viral load.

 

We consider the treatment a failure if the virus increases after 2 weeks of treatment or does not decrease sufficiently.

 

This could be due to the virus itself being genetically resistant to antivirals or the patient's poor medication adherence to antivirals.” "After developing a resistance, patients may use the same drug again or consider using second-line options such as foscarnet or cidofovir.

 

However, there are limitations to the use of these agents because of their severe nephrotoxicity, which can be fatal in kidney transplant patients." Livtencity enters the scene...showing promise in patients with resistant CMV Livtencity is the drug that can address these concerns.

 

It works by inhibiting a kinase called UL97 that allows the virus to multiply inside the cellular host.

 

The drug’s efficacy and safety compared to existing treatment were confirmed through the Phase III SOLSTICE study.

 

Study results showed that Livtencity demonstrated a CMV viremia clearance rate of 55.7%, more than double the 23.9% achieved with valganciclovir/ganciclovir, foscarnet, or cidofovir arms that used the drugs alone or in combinations.

 

Also, Livtencity is associated with fewer side effects compared to existing therapies.

 

Patients taking immunosuppressants after transplant often have poor kidney function, and Livtencity reduced their dosing burden with its low toxicity.

 

In terms of safety, Livtencity was associated with a 1.7% incidence of neutropenia.

 

This was 15 times lower than the 25.0% in the ganciclovir/valganiclovir arm.

 

"The negative conversion rate was better in the Livtencity arm, and the Livtencity arm also showed a significantly higher negative conversion rate at 16 weeks of follow-up.

 

It also showed a lower rate of adverse events such as neutropenia and nephrotoxicity, with very few discontinuations due to adverse events being reported.

 

Livtencity’s developer Takeda’s reimbursement application for its drug had passed the Drug Reimbursement Review Committee in December last year and the company has been negotiating drug prices with the National Health Insurance Service since this month.

 

Professor Shin stressed that insurance reimbursement is necessary for Livtencity’s broader use to benefit more patients.

 

Professor Shin emphasized, "CMV is a virus that has a significant adverse effect on the survival rate of all transplant recipients, even among the opportunistic infections that can occur with solid organ transplant and hematopoietic stem cell transplants.

 

Delaying its treatment increases the risk of rejection, therefore, early and effective treatment is very important." He added, "In this regard, we should welcome the introduction of a new class of antivirals for resistant and treatment-refractory CMV, as it is a blessing for transplant patients in practice.

 

Insurance coverage for the drug is all that more important as it relieves the Livtencity’s burden of cost for healthcare providers and patients in Korea."