Shares of San Diego-based Vical Inc. (NASDAQ:VICL) fell 23 percent, or 43 cents, to $1.44 Monday as longtime partner Astellas Pharma Inc. took the wraps off top-line data showing that ASP-0113, a vaccine designed to prevent cytomegalovirus (CMV) disease and associated complications in hematopoietic stem cell transplant (HCT) recipients, failed to meet primary or secondary endpoints of the phase III study. It’s the second major stumble for the vaccine following a 2016 phase II miss in kidney transplant patients.
The top-line phase III outcome proves a stark contrast to Vical’s 2009 phase II readout, which showed CMV-seropositive HCT recipients randomized to treatment with the vaccine experiencing significant reductions in key viral reactivation metrics vs. placebo-treated patients.
Ahead of the readout, Astellas had expressed hope for commercializing the vaccine, also known as Transvax, in North America, Europe and Asia. Now the company is working through an assessment of detailed data from the study, Salim Mujais, Astellas’ senior vice president of global therapeutics, told BioWorld. “At this point, we cannot comment on further plans,” he said.
CMV is a ubiquitous herpes virus that is estimated to infect more than half of all U.S. adults by age 50, with infection rates reaching as high as 98 percent in some South Asian populations, according to a Cortellis disease report. In the transplant setting, incidence varies as a factor of type of organ involved, serostatus of recipient and donor, and prevention strategies employed. The DNA virus often lies latent, but is sometimes reactivated during immunosuppressive therapy provided after organ transplants, putting patients at risk for end-organ disease and death.
The phase III Helios trial sought to determine whether ASP-0113 could prevent CMV reactivation in 515 HCT recipients with a primary endpoint consisting of a composite evaluation of overall mortality and CMV end-organ disease assessed one year after transplantation.
Secondary endpoints of the trial included time to first protocol-defined CMV viremia; time to first adjudicated CMV-specific antiviral therapy; and time to first CMV-specific antiviral therapy for protocol-defined CMV viremia or CMV end-organ disease.
Astellas made a $10 million payment to Vical in 2012 upon finalization of the phase III trial design.
But, while the vaccine was generally well tolerated, it failed to meet any of the study’s endpoints. (See BioWorld Today, June 26, 2013.)
Vical did not respond to a request for comment. However, in past regulatory filings it has said its revenues are largely dependent on manufacturing and research services performed under its license agreement with Astellas.
Asked whether there were any common factors that may have led to the failure of ASP-0113 to meet the endpoints of both the phase III hematopoietic stem cell transplant study and the phase II solid organ transplant (SOT) study, Astellas’ Mujais pointed out that there were numerous differences between the two development programs, including differing immunosuppressive regimens, different dosing, different CMV serostatus of the recipient population, and different endpoints. Furthermore, he pointed out, “HSCT patients require a shorter and less intense duration of immunosuppression than an SOT patient.”
ASP-0113 is part of a deal Vical and Astellas originally announced in July 2011. Back then, expectations for the HCT trial were that it would be completed with top-line data in 2013. However, as a large phase III trial with hundreds of subjects and enrollment in 11 countries, it proved a difficult patient population to enroll and also faced competing studies at trial sites, Mujais said. (See BioWorld Today, July 18, 2011.)
The vaccine is designed as a bivalent DNA vaccine encoding CMV phosphoprotein 65 and glycoprotein B antigens to induce both cellular and humoral immune responses.
It was the first CMV vaccine to demonstrate an ability to protect immunocompromised HCT recipients in a randomized phase II study.
At 12 months post-transplant, the incidence of CMV viremia – defined as 1,500 copies or more of CMV virus per mL of blood – was 32 percent in the treatment group vs. 62 percent in the placebo group (p = 0.08). The prevalence of viremia episodes over the trial period also was significantly lower in the ASP-0113 group vs. placebo (p = 0.036.) (See BioWorld Today, Sept. 20, 2016.)
Outside the hit to its share price, the long-term impact of Helios’ failure on Vical wasn’t immediately clear. The company priced a $25 million underwritten public offering of its shares at $1.75 per share on Nov. 8. It has not yet announced the closing of the offering.
As of Monday, Vical’s web site noted that it was looking for the best way to advance a phase I trial of Cymvectin, its wholly owned prophylactic vaccine intended to elicit CMV immunity in women before they become pregnant, thereby reducing the possibility of transmitting CMV to a fetus during pregnancy. It also said, in its public offering filing, that it was running a phase II trial of VCL-HB01, another DNA vaccine targeting the reduction of genital herpes lesion recurrences caused by herpes simplex virus type 2, or HSV-2, infection. The company was planning to initiate a phase II trial for VL-2397 – a candidate in-licensed from Astellas – for the treatment of invasive aspergillosis in acute leukemia patients and allogeneic HCT recipients. Mujais said that program was not impacted by the results of the Helios trial.
In its latest quarterly report, Vical reported having cash of about $10.2 million as of Sept. 30, 2017.