US FDA approves Takeda’s Livtencity to treat people with post-transplant Cytomegalovirus infection

Takeda Pharmaceutical yesterday announced that the US Food and Drug Administration (FDA) has approved Livtencity (maribavir) for the treatment of adults and pediatric patients (12 years of age or older and weighing at least 35 kg) with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir, or foscarnet. Overall, more than twice the proportion of adult transplant patients with refractory or resistant (R/R) CMV infection/disease achieved confirmed CMV DNA level <LLOQ (lower limit of quantification, i.e. <137 IU/mL) at week eight (end of treatment phase), the study’s primary endpoint, with Livtencity (56%; n=131/235), compared to those treated with conventional antiviral therapies (24%; n=28/117) (adjusted difference: 33%, 95% CI: 23–43; p<0.001). Livtencity is Takeda’s second new molecular entity to receive FDA approval in FY2021, the company said via a statement.

“The announcement redefines the management of post-transplant CMV with the approval of the first and only treatment for transplant patients with CMV that is refractory with or without resistance, a significantly underserved and vulnerable patient community,” said Ramona Sequeira, President, US Business Unit and Global Portfolio Commercialisation, Takeda Pharmaceutical.

“People undergoing transplants have a lengthy and complex healthcare journey; with the approval of this treatment, we’re proud to offer these individuals a new oral antiviral to fight CMV infection and disease. We are grateful for the contributions of the patients and clinicians who participated in our clinical trials, as well as the dedication of our scientists and researchers,” Sequeira added.

Livtencitty is a new molecular entity which targets CMV at pUL97, resulting in inhibition of viral DNA replication, encapsidation and nuclear egress. Though a rare disease, CMV is one of the most common infections experienced by transplant recipients, with an estimated incidence rate of around 16-56 per cent in Solid Organ Transplant (SOT) recipients and 30-70 per cent in Hematopoietic Stem Cell Transplant (HSCT) patients. CMV can be acquired or reactivated following transplant leading to serious consequences—including loss of the transplanted organ and failure of the graft—or loss of life, the statement added.

According to the statement, Livtencity will be available in the coming days. For appropriate patients, physicians can submit a prescription to initiate access to treatment by contacting Takeda Patient Support at 1-855-268-1825.

“The FDA approval of Livtencity marks a major step forward in the treatment of post-transplant CMV, bringing a new therapeutic option to those living with this potential life-threatening opportunistic infection,” said Roy F Chemaly, MD, MPH, FACP, FIDSA, Department of Infectious Diseases, Infection Control and Employee Health at The University of Texas, MD, Anderson Cancer Center in Houston, TX.

“In clinical studies, we observed Livtencity was statistically superior to conventional antiviral therapies in achieving the primary endpoint at week eight.”

Prior to FDA approval, Livtencity (maribavir) was granted Orphan Drug Designation by the FDA for treatment of clinically-significant CMV viremia and disease in at-risk patients, as well as Breakthrough Therapy Designation as a treatment for CMV infection and disease in transplant patients resistant or refractory to prior therapy. Takeda is looking forward to continuing our discussions with regulatory agencies across the globe to potentially bring maribavir to patients worldwide. The company is also investigating maribavir as a first-line treatment of CMV in hematopoietic stem cell transplant recipients in an ongoing phase-III clinical trial.

The statement also mentioned that Livtencity was evaluated in the TAK-620-303 (SOLSTICE) trial, a global, multi-centre, randomised, open-label, active-controlled superiority trial assessing the efficacy and safety of treatment with either maribavir or investigator-assigned treatment (IAT, conventional antiviral therapy) in 352 HSCT and SOT adult recipients with CMV infection refractory, with or without or resistance, to one or a combination of conventional antiviral therapies: ganciclovir, valganciclovir, foscarnet, or cidofovir. Participants were randomised 2:1 to receive maribavir (N=235) (400 mg, twice daily) or IAT (N=117) (as dosed by the investigator) for up to eight weeks. After completion of the treatment period, subjects entered a 12-week follow-up phase. The primary efficacy endpoint was confirmed CMV DNA level <LLOQ (lower limit of quantification, [i.e. <137 IU/mL] as assessed by COBAS AmpliPrep/COBAS TaqMan CMV test at the end of week eight).

The most common adverse events occurring in all grades, >10 per cent of patients receiving maribavir were taste disturbance, nausea, diarrhoea, vomiting, and fatigue. A higher proportion of subjects in the IAT group discontinued study medication due to an adverse event compared to the Livtencity group (32%, n=37/116 versus 13%, n=31/234, respectively). Taste disturbance events (46%, n=108/234) were generally mild, and rarely led to discontinuation of maribavir (one per cent). In 37 per cent of patients, these events resolved while patients remained on therapy (median duration 43 days; range seven to 59 days). For the patients with ongoing taste disturbance after drug discontinuation, resolution occurred in 89 percent. In patients with resolution of symptoms after drug discontinuation, the median duration of symptoms of treatment was six days (range two to 85 days). All-cause mortality was similar in each treatment group (Livtencity 11%, n=27/235; IAT 11%, n=13/117), the statement concluded.