Vical's TransVax CMV vaccine achieves key endpoints in Phase 2 trial in immunocompromised HCT recipients

Vical Incorporated (Nasdaq:VICL) announced today the achievement of key efficacy, immunogenicity and safety results in a Phase 2 trial, establishing its TransVax™ cytomegalovirus (CMV) vaccine as the first to provide evidence of protection in immunocompromised hematopoietic cell transplant (HCT) recipients, and defining a potential pathway for further development.

"The TransVax™ vaccine has demonstrated the ability to drive effective immune responses in the inherently difficult therapeutic setting of immunocompromised patients," said CMV and organ transplant expert Mark D. Pescovitz, M.D. "In addition to providing evidence of protective efficacy in HCT recipients, the TransVax™ Phase 2 results have identified clinically relevant endpoints that may be appropriate for further development."

"We look forward to finalizing our approach through discussions with CMV and transplant experts, and reviewing our resulting plans with the regulatory agencies," said Richard T. Kenney, M.D., Vical's Vice President of Clinical Development, who will present the data at 11:15 a.m. EDT Tuesday at the 50^th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (Boston – September 12-15). Dr. Pescovitz, Professor of Surgery and Microbiology & Immunology, and Vice Chair of Research in Surgery at the Indiana University School of Medicine, will join Vical management on a concurrent conference call and webcast for the investment community.

Efficacy Results

The TransVax™ Phase 2 trial was a 1:1 randomized, double-blind, placebo-controlled, multi-center study in 80 patients scheduled to receive HCTs for their underlying leukemias or lymphomas. Through 12 months post-transplant, significant reductions were achieved for key viral reactivation metrics:

• The incidence of CMV viremia (percentage of subjects with ≥500 copies of CMV virus per mL of blood by a central lab assay) was 32% in the TransVax™ group, and 62% in the placebo group>);
• The median time to initial viremia was >365 days (i.e., median not reached during the 12-month study period) for the TransVax™ group, and 109.5 days for the placebo group>);
• The number of CMV viremia episodes (0-4 per subject) was significantly lower for the TransVax™ group than for the placebo group>);
• The duration of viremia was lower for the TransVax™ group than for the placebo group (mean of 10.6 days vs. mean of 19.5 days, respectively;>), and significantly lower as a percentage of the time subjects spent on study (mean of 4.9% vs. mean of 7.7%, respectively;>); and
• The prevalence of CMV viremia episodes over the trial period was significantly lower for the TransVax™ group than for the placebo group>).

Antiviral therapy use was triggered by site-specific treatment practices based on local lab assays, which impeded comparability among the 16 enrolling U.S. sites. Overall, 48% of subjects in the TransVax™ group vs. 62% of subjects in the placebo group received antiviral drugs for CMV during the study. The median duration of antiviral treatment was approximately 30 days in the TransVax™ group vs. approximately 40 days in the placebo group. Because antiviral drugs are used preemptively to control CMV outbreaks, CMV-associated disease is rare and the study was not powered to detect a difference in this endpoint. Only three of 40 subjects (8%) in the TransVax™ group and four of 34 subjects (12%) in the placebo group developed CMV-associated disease. Antiviral drug usage and CMV-associated disease are not practical endpoints for future studies.

Immunogenicity Results

Published data have shown that T-cell responses are critical for controlling CMV reactivation; antibody responses may provide additional protection. The HCT recipients in the study all had preexisting CMV infections and therefore would be expected to have baseline immune responses against CMV. They were also immunosuppressed as a result of treatments for their underlying leukemias or lymphomas. Despite these challenges:

• T-cell responses to phosphoprotein 65 (pp65) were significantly higher in the TransVax™ group than in the placebo group over the one-year trial>);
• T-cell and antibody responses to glycoprotein B (gB) were higher in the TransVax™ group than in the placebo group and trending toward greater separation over the one-year trial.

Safety Results

The TransVax™ vaccine was well tolerated in the Phase 2 trial in immunocompromised HCT recipients, and no safety concerns were raised during the trial. There was no significant difference in the number of serious adverse events (SAEs) between the TransVax™ and placebo groups. There also were fewer deaths in the TransVax™ group (18%) than in the placebo group (32%) during the trial.