Phase 3 data supported the FDA in their decision to grant priority review to a new drug application for maribavir as therapy for certain patients with cytomegalovirus following transplant.
A new drug application was granted priority review by the FDA for maribavir as therapy to treat patients with refractory cytomegalovirus (CMV) infections with or without resistance following either solid organ or hematopoietic stem cell transplant (HSCT), according to Takeda Pharmaceutical Company Limited, who is responsible for developing the agent.1
The application was based on data from the phase 3 TAK-620-303 (SOLSTICE) trial (NCT02931539) examining the orally bioavailable anti-CMV compound versus investigator-assigned therapy in patients with transplant recipients with cytomegalovirus (CMV) infections that are refractory or resistant to treatment with ganciclovir, valganciclovir, foscarnet, or cidofovir.
“CMV is one of the most common viral infections experienced by transplant recipients, and current antiviral treatment options are limited, and physicians have to engage in a careful balance of viral clearance and side effect management that can impact patient care and transplant outcomes,” Obi Umeh, MD, vice president and Maribavir global program leader with Takeda, said in a press release. “If approved, maribavir has the potential to change the treatment landscape for post-transplant CMV, and the acceptance of this regulatory application is an important milestone on maribavir’s path forward.”
Results from the supporting multicenter, randomized, open-label, active-controlled trial were presented earlier in the year at the 2021 Transplantation & Cellular Therapy (TCT) Meetings Digital Experience.2 Patients were subject to a 2-week screening period followed by randomization (2:1) to either maribavir at 400 mg (n = 235) or investigator’s choice of therapy (n = 117) for 8 weeks plus 12 weeks of follow-up.
The primary end point was the proportion of patients achieving confirmed CMV viremia clearance, defined as plasma CMV DNA less than 137 IU/mL by 2 consecutive tests 5 days apart or more. The key secondary end point was the proportion of patients with CMV viremia clearance and symptom control at the end of week 8 through week 16.
Maribavir led to a statistically significant boost in patients achieving the primary end point, with 55.7% having viral clearance at week 8 versus just 23.9% of those on conventional therapies (P <.001).
Analysis of the primary outcome revealed that 55.6% of patients receiving solid organ transplant with relapsed or refractory CMV infection/disease receiving maribavir achieved confirmed CMV viremia clearance compared with 26.1% of those in the control arm. In patients with HSCT, the rates were 55.9% and 20.8%, respectively. When considering baseline viral loads (<9000 IU/mL or ≥9000 IU/mL), more patients achieved clearance of CMV at week 8 when treated with maribavir (62.1% and 43.9%, respectively) versus investigator’s choice of therapy (24.7% and 21.9%).
For the secondary end point, 18.7% of patients treated with maribavir maintained CMV viremia clearance and symptom control through week 16 versus 10.3% of those treated with conventional therapies (P = .013).
Additionally, patients who received maribavir had fewer treatment-related adverse effects (AE) versus control therapy, including lower rates of neutropenia compared with valganciclovir/ganciclovir (1.7% vs 25%, respectively) and acute kidney injury versus foscarnet (1.7% vs 19.1%). Treatment-emergent (TE)AEs of any grade occurred in 97.4% of those receiving maribavir and 91.4% of the conventional therapy group. Drug discontinuations resulting from TEAEs occurred in 13.2% and 31.9% of patients, respectively.
“CMV infection puts transplant recipients at an increased risk of disease, such as pneumonia or gastrointestinal disease. It can also increase the risk of graft rejection, opportunistic co-infections, and in some cases, even death,” Michael Boeckh, MD, PhD, head of Infectious Disease Sciences Program at the Vaccine and Infectious Disease Division of Fred Hutchinson Cancer Research Center, said in a press release. “The results of the SOLSTICE trial are promising and show that maribavir may help with post-transplant CMV viremia, including cases of drug-resistance for which there is an unmet need.”
1. U.S. Food & Drug Administration Grants Priority Review of Maribavir for the Treatment of Post-Transplant Recipients With Cytomegalovirus Infection in Those Resistant and/or Refractory to Prior Anti-CMV Treatment. News release. Takeda Pharmaceutical Company Limited. May 21, 2021. Accessed May 21, 2021. https://bit.ly/3hJDlrq
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 May 21, 2021. https://bit.ly/3c2cwuX