Vical reports top-line results from Phase I/II trial of therapeutic genital herpes vaccine

The trial enrolled patients across seven U.S. sites and is evaluating two constructs: a monovalent (gD) vaccine and a bivalent (gD + UL46) vaccine, each formulated with Vical’s proprietary Vaxfectin adjuvant.

The top-line analysis compared pre-vaccination measurements for each arm with those taken during the swabbing period in months 2 and 3 following the last vaccine dose. Neither the monovalent nor bivalent vaccine met the primary endpoint.

On prospectively defined secondary endpoints, the bivalent vaccine achieved statistically significant reductions in the rate of genital lesions (-51%, p = 0.0037) and viral load from positive swabs (-0.39 log10, p = 0.0008) versus baseline.

Both the monovalent and bivalent vaccines were generally well tolerated. Safety data have been reviewed throughout the trial by an independent safety monitoring board, and no grade 4 adverse events or serious adverse events related to vaccination have been observed.

"We just received the top-line study data and we are disappointed that the vaccines did not meet the primary endpoint," said Vijay Samant, President and Chief Executive Officer.

"The trial is ongoing and all patients are being followed for safety for 12 months and efficacy for 9 months after their final vaccine dose. During that 9-month period, 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. We greatly appreciate the ongoing support of the patients and investigators who are taking part in this trial."

Mr. Samant continued, "In the meantime, we remain focused on advancing our CMV vaccine candidate partnered with Astellas. Enrollment is complete in the Phase 2 solid organ transplant trial, placing us on track for data during the second half of 2016, and the Phase 3 pivotal trial is underway in hematopoietic stem cell transplant recipients. We are also moving our in-licensed antifungal compound toward a Phase 1 trial initiation 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."

The Phase 1/2 trial is an ongoing randomized double-blind, placebo controlled study which enrolled 165 symptomatic HSV-2 patients at seven investigational sites in the U.S. The trial consists of an initial dose escalation cohort with 14 patients and then an efficacy cohort with 151 patients at full dose. 131 evaluable patients are included in the top-line per protocol efficacy analysis.

Enrolled patients are required to have a history of symptomatic genital herpes with 2 to 9 lesion recurrences per year. The dose escalation component of the trial assessed the safety of 1/4 dose, 1/2 dose, and a full dose of vaccines in a small number of patients prior to dosing additional patients at the full dose. Two vaccine constructs are being evaluated: monovalent (gD) and bivalent (gD + UL46), each formulated with Vical’s proprietary Vaxfectin(R) adjuvant.

Regardless of the vaccine construct and dose, all patients received a vaccine or a placebo on days 0, 28, and 56. The patients in the efficacy cohort who received the full dose of vaccine or placebo are assessed for vaccine effectiveness in reducing HSV-2 shedding from baseline as the primary endpoint, and for secondary endpoints including changes in lesion rate and viral load from baseline.

Each patient in the efficacy cohort performed once daily swabbing to measure HSV shedding before and after vaccination. Sampling periods of 60 days for daily swab collections and diaries were used to generate shedding and lesion data to compare the post-vaccination to the pre-vaccination periods.

In addition, the quantity of virus during each positive shedding day was compared for each patient pre- and post-vaccination. All patients in the trial continue to be followed for safety for 12 months and efficacy for 9 months after their final vaccine dose, and during that 9-month period, additional clinical efficacy data including recurrence rate and lesion rate will be evaluated.