Vical has acknowledged that both the monovalent and bivalent forms of its genital herpes vaccine candidate missed their primary endpoints in a Phase I/II trial, based on topline results.
The monovalent and bivalent vaccines—both formulated with Vical's Vaxfectin® adjuvant—failed to show statistically significant improvement over placebo in reducing viral shedding in herpes simplex virus type 2 (HSV-2) infected patients, the company said yesterday afternoon after the close of financial markets.
The topline analysis compared prevaccination measurements for each treatment arm with those taken during the swabbing period in months 2 and 3 following the last vaccine dose.
Bivalent vaccine showed a 19% decrease in the shedding rate from baseline, compared to 45% for placebo. Monovalent vaccine performed even worse, with a 12% decrease.
“We are disappointed that the vaccines did not meet the primary endpoint,” Vijay Samant, Vical’s president and CEO, said in a statement.
Vical added that the bivalent vaccine achieved statistically significant reductions in two secondary endpoints—the rate of genital lesions (–51%) and change in viral load from positive swabs compared with baseline, measured in HSV copies, log10 (–0.39).
Both the monovalent and bivalent vaccines were generally well tolerated, Vical said, adding that no grade 4 adverse events or serious adverse events related to vaccination had been observed.
The ongoing randomized double-blind study enrolled 165 symptomatic HSV-2 patients at seven U.S. sites. The trial consists of an initial dose escalation cohort with 14 patients, followed by an efficacy cohort with 151 patients at full dose. The topline analysis was based on results from 131 evaluable patients.
Enrolled patients were required to have a history of symptomatic genital herpes with two to nine lesion recurrences per year. The trial’s dose escalation component assessed the safety of a quarter dose, a half dose, and a full dose of vaccine in a small number of patients before additional patients were dosed at the full dose.
Samant added that the trial was ongoing. All patients will continue to be assessed for safety for 12 months, and for efficacy for 9 months, after their final vaccine dose. “During that nine-month period,” Samant noted, “we will collect additional clinical efficacy data, including recurrence rate and lesion rate, which will enable us to determine the appropriate next steps for this program.”
In the meantime, Samant said, Vical would continue to advance the CMV vaccine candidate the company is co-developing with Astellas Pharma. According to Vical, enrollment is complete in the Phase II solid organ transplant trial, placing the company on track to generate data during the second half of 2016, while a Phase III trial is underway in hematopoietic stem cell transplant recipients.
Vical said it is also advancing its in-licensed antifungal compound toward a Phase I trial set to launch during the first half of 2016.
“Because Astellas funds the CMV program, and given the other operational efficiencies we have put in place, we anticipate that our current cash position will fund us through these milestones and into 2017,” Samant predicted.
Those efficiencies include the layoff of 47 employees, which occurred in 2013 after Vical ended development of its lead drug Allovectin® (velimogene aliplasmid) for metastatic melanoma. The company gave up on Alloectin after the cancer immunotherapy candidate failed to meet efficacy endpoints in a Phase III clinical trial.