CMV Vaccine Falls Short in Phase III Trial

ASP0113, an investigational DNA vaccine developed for cytomegalovirus-seropositive hematopoietic stem cell transplant patients, has failed to meet its primary and secondary endpoints.

Vijay Samant

ASP0113, an investigational DNA vaccine developed for cytomegalovirus (CMV)-seropositive hematopoietic stem cell transplant (HSCT) patients, has failed to meet its primary and secondary endpoints in results from the phase III HELIOS trial.1

The vaccine missed its primary efficacy endpoint, determined by a composite of overall mortality and CMV end organ disease through 1 year post-transplant. ASP0113 also failed to meet the secondary endpoints of time to first protocol-defined CMV viremia and time to first use of adjudicated CMV-specific antiviral therapy.

Tokyo-based Astellas Pharma developed ASP0113 in partnership with Vical Incorporated, a biopharmaceutical firm headquartered in San Diego, California. The companies issued a joint press release announcing top-line results.

“The phase III trial outcome is disappointing,” Vical CEO Vijay Samant said in a statement. “Astellas and Vical employees, the investigators, and study site personnel did an outstanding job conducting this study, but unfortunately, the vaccine was unable to provide protection against all-cause mortality in this very difficult-to-treat patient population.”

CMV is a herpes virus estimated to infect more than half of US adults by age 50, and the virus is even more prevalent in developing countries. A healthy immune system typically protects against CMV disease, but does not prevent or clear latent infection. People with compromised immune systems are at high risk for CMV reactivation, which can lead to severe illness or death. Those at greatest risk include HCT and solid-organ transplant recipients, as well as infants born to mothers who become infected during pregnancy.

Investigators initiated the randomized, double-blind, placebo-controlled HELIOS (N = 514) in 2013 to evaluate the efficacy of ASP0113.

“We are disappointed that the results did not demonstrate a significant improvement in overall survival and reduction in CMV end-organ disease,” Bernhardt G. Zeiher, president of Development, Astellas, said in a statement. “We would like to thank the patients and clinicians who participated in this important trial.”

Astrellas and Vical said injection-site reactions were the most common adverse event, but the vaccine was generally well tolerated. They did not release any further details.

This is the second time ASP0113 has failed in a clinical trial.2 In 2016, Astellas and Vical announced that the vaccine did not meet its primary endpoint, the proportion of patients having CMV viremia defined as a plasma viral load of ≥1000 IU/mL by central laboratory assay through 1 year after first injection, in a phase II study. ASP0113 also failed to meet secondary endpoints for CMV-associated disease and CMV-specific antiviral therapy as assessed by an independent, blinded adjudication committee.

The phase II study was a randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of ASP0113 in CMV-seronegative kidney transplant patients who received an organ from a CMV-seropositive donor. The patient population included 150 kidney transplant recipients across approximately 80 centers in North America, Europe, and Australia. Participants were randomly assigned to either ASP0113 or placebo plus valganciclovir or ganciclovir prophylaxis for 100 days after kidney transplant.

In the phase II trial, the safety profiles were generally similar between treatment groups, but local injection site reactions were more common in the ASP0113 treatment group.


  1. Astellas and Vical Announce Top-Line Results for Phase 3 Trial of Cytomegalovirus Vaccine ASP0113 in Hematopoietic Stem Cell Transplant Recipients. Astellas Pharma Inc. and Vical Incorporated. Published and accessed January 18, 2018.
  2. Vical and Astellas Announce Topline Results from a Phase 2 Study of Investigational Cytomegalovirus (CMV) Vaccine (ASP0113) in Kidney Transplant Patients. Astellas Pharma Inc. and Vical Incorporated. Published September 19, 2016. Accessed January 18, 2018.