The race for a cytomegalovirus (CMV) vaccine hit a stumbling block on 22 January, when Astellas and Vical announced that their investigational DNA vaccine ASP0113 had failed a pivotal Phase III study. Although well-tolerated in target hematopoietic stem cell transplant (HSCT) patients, the vaccine fell short of its primary and secondary endpoints, showing no difference in overall survival and reduction of CMV end-organ disease compared to placebo.
The failure of Astellas/Vical opens the door for Helocyte – a private subsidiary of Fortress Biotech that possesses two clinical-stage vaccines – to be the first developer to bring a licensed CMV vaccine to market.
Infection with CMV is ubiquitous and typically asymptomatic in the majority of individuals. However, individuals with compromised immune systems can develop serious morbidities as a consequence of CMV infection, including invasive CMV disease and end-stage organ disease.
HSCT and solid organ transplant (SOT) patients undergoing immunosuppression therapy are especially susceptible to CMV disease arising from primary infection or reactivation of latent CMV. Moreover, maternal transmission of CMV from mother to foetus can produce congenital CMV infections, a leading cause of neurological and developmental disabilities in children.
Vaccine development issues
Vical developed ASP0113 as a DNA vaccine, designed to induce an immune response against the CMV antigens pp65 and glycoprotein B. In 2011, Vical began a partnership with Astellas to advance ASP0113 through clinical trials for prevention of CMV viremia in transplant patients.
A setback came in 2016, when the vaccine failed to show improvements over placebo in a Phase II trial in kidney transplant patients. Nevertheless, Astellas and Vical advanced their candidate into a Phase III study enrolling 514 individuals across 70 sites, hoping for more favourable efficacy data in HSCT patients. The disappointment of this study likely spells the discontinuation of their ASP0113 program.
The field of CMV vaccine research and development is no stranger to obstacles. Early efforts with live attenuated viruses, including the Towne strain vaccine from MedImmune (a subsidiary of AstraZeneca), failed to protect patients from CMV infection due to lack of immunogenicity. Other promising approaches, including chimeric vaccines and subunit vaccines that target individual viral proteins, have yet to reach Phase III. In lieu of a standard CMV vaccine, physicians have taken a prophylactic approach with antiviral drugs for high-risk patient populations, at the expense of potentially severe toxicities.
Helocyte is now positioned to take the lead in the CMV vaccine race, advancing two vaccine candidates in an otherwise sparse Phase II field. One lead vaccine (Triplex) consists of inactivated, modified vaccinia Ankara (MVA) viral vector encoding three CMV tumor-associated antigens, for prevention of CMV infection in HSCT patients. The other (PepVax) is a human leukocyte antigen-restricted peptide vaccine consisting of a mutated CMV epitope (pp65) with potential immunostimulatory activities.
Both vaccines performed well in Phase I safety studies, and Phase II results for Triplex are expected to be announced by April 2018. By leveraging two differing vaccine strategies, Helocyte has established broader potential avenues of success, but will likely need to secure a partnership with big pharma to commercialise an approved product.
GlobalData (2018). Expert Insight: Shire’s Breakthrough Therapy Maribavir Has Potential to Shake Up the Cytomegalovirus Market, January 2018, GDHC1549EI
GlobalData (2018). OpportunityAnalyzer: Cytomegalovirus (CMV) – Opportunity Analysis and Forecasts to 2027, to be published