Vaccine Fails to Help CMV-Positive Stem-Cell Recipients

ASP0113 missed key endpoints in phase 3 trial

ASP0113 (Astellas Pharma Inc./ Vical Incorporated), an investigational DNA vaccine being developed for cytomegalovirus (CMV)-seropositive hematopoietic stem cell transplant recipients, did not significantly improve overall mortality and CMV end-organ disease through the first year following the transplant, the companies announced.

ASP0113 failed to meet its primary or secondary endpoints in the phase 3 HELIOS clinical trial, which was designed to evaluate the vaccine’s efficacy compared with placebo in CMV-seropositive recipients undergoing an allogeneic stem cell transplant. Efficacy was assessed using a primary composite endpoint of overall mortality and CMV end-organ disease through the first year following the transplant, an endpoint which was not met. Secondary endpoints of time to first protocol-defined CMV viremia and time to first use of adjudicated CMV-specific antiviral therapy also were not met.

Both companies expressed disappointment with the results in what Vijay Samant, Vical's Chief Executive Officer, described as a “very difficult-to-treat patient population."

The companies did not release detailed efficacy results. The vaccine was generally well tolerated, with injection-site reactions being the most commonly reported adverse event.

The phase 3 trial was a 1:1 randomized, double-blind, placebo-controlled study that enrolled 514 CMV seropositive subjects undergoing hematopoietic stem cell transplantation. Randomization was stratified by donor-recipient relatedness and donor CMV serostatus. Subjects were followed for one year post-transplant.

CMV is a herpes virus that is estimated to infect more than half of all adults in the United States by age 50, and is even more widespread in developing countries. A healthy immune system typically protects an infected person against CMV disease, but does not prevent or clear latent infection. Individuals whose immune systems are not fully functional are at high risk of CMV reactivation, potentially leading to severe illness or death. Those at greatest risk include HCT and solid-organ transplant recipients, as well as infants born to mothers who first become infected during pregnancy.

ASP0113 is an investigational vaccine candidate designed to prevent CMV disease and associated complications in CMV-seropositive HCT recipients. ASP0113 is a bivalent DNA vaccine encoding CMV phosphoprotein 65 and glycoprotein B antigens for induction of both cellular and humoral immune responses, formulated with a proprietary poloxamer-based delivery system. ASP0113 was initially developed by Vical, which partnered with Astellas for further development and commercialization. ASP0113 received orphan drug designation in the United States and Europe.

Source: Astellas Pharma Inc.; January 22, 2018.