Abandoned Genital Herpes Vaccine GEN-003 Found to Reduce Lesions, Decrease Viral Shedding at Varying Doses

GEN-003, a vaccine comprised of a transmembrane deletion mutant of glycoprotein D and a saponin-derived adjuvant, is clinically effective at doses of 60 µg/50 µg and 60 µg /75 µg for reducing viral shedding at up to 1 year in adults with symptomatic genital herpes simplex virus 2 (HSV-2) infection, according to a study in The Journal of Infectious Diseases (JID). Additionally, the investigators saw a reduction in lesion rates following administration of GEN-003 at varying doses of the study vaccine.

“Currently available therapeutic options for recurrent HSV-2 infections include short-term treatment beginning with the first signs of recurrence, or chronic daily suppression with nucleoside analogues, valacyclovir, acyclovir, or famciclovir,” the investigators, led by Nicholas Van Wagoner, MD, PhD, of the University of Alabama at Birmingham, wrote. “However, chronic daily therapy does not completely suppress outbreaks, has cost implications, and requires daily adherence. With a high global prevalence, an established link between HSV-2 and subsequent HIV acquisition, the often overlooked psychological effects of genital HSV infection, and the inability of antiviral oral treatments to completely eliminate viral shedding, there is a clear need for new therapeutic options.”

Adult patients between 18 and 50 years of age with genital HSV-2 for more than 1 year were enrolled in this randomized, placebo-controlled study (N = 310). Investigators randomized patients to normal saline placebo (n = 45) or GEN-003 vaccine doses of either 30 µg/25 µg (n = 44), 30 µg/50 µg (n = 45), 30 µg/75 µg (n = 44), 60 µg/25 µg (n = 44), 60 µg/50 µg (n = 44), or 60 µg/75 µg (n = 44). Participants were given 3 intramuscular infections of their assigned dose every 21 days. The investigators compared each dose in regard to the participants’ associated rates of viral shedding at baseline and following the 3-dose treatment regimen.

At baseline, the viral shedding rates were 22.2% for placebo and between 13.6% and 27.1% for the active doses. Approximately 12 months following the last dose, significant reductions in viral shedding were found for the 30/75 dose (rate ratio [RR] 0.34; 95% CI 0.1-0.61); P =.0003), 60/50 dose (RR 0.38; 95% CI 0.25-0.57; P <.0001), and 60/75 dose (RR 0.43; 95% CI 0.23-0.82; P =.01). According to a ranking analysis of the change from baseline to the immediate post-vaccination period, both the 60/50 and 60/75 dosing combinations demonstrated the greatest viral shedding reductions.

In regard to lesion reduction at 12 months, significant reductions from baseline were observed for patients receiving GEN-003 vaccine doses of 30/50 (RR 0.42; 95% CI 0.18-0.96; P =.04), 30/75 (RR 0.46; 95% CI 0.23-0.92; P =.03), 60/25 (RR 0.42; 95% CI 0.21-0.83; P =.01), 60/50 (RR 0.35; 95% CI 0.18-0.71; P =.003), and 60/75 (RR 0.53; 95% CI 0.31-0.89; P =.02). There were no incidents of serious adverse events immediately after treatment or at 1 year with any of the vaccination doses.

“GEN-003 reduced viral shedding for up to 12 months following completion of a 3-dose series, with the 60/50 and 60/75 doses representing the most promising combinations for further evaluation based on viral shedding and overall safety assessment,” the study investigators summarized. “We selected viral shedding as the primary parameter for comparison because it is an objective measure of antiviral effect and underlies the key elements of genital HSV infection: recurrences and transmission to an uninfected sexual partner.”

The researchers of this study lacked placebo data after 28 days of treatment, limiting the availability of comparator data in regard to long-term reactogenicity. Further research with a larger sample size may be necessary to determine the effects of the vaccine in specific subsets and demographics of the HSV-2 population.

Previous studies on GEN-003 revealed 3 injections of the vaccine resulted in significant clinical improvements in participants when compared with baseline. Viral shedding was reduced by 66%, and genital lesion rate was reduced by 65%. Furthermore, 30% of participants remained lesion free for 12 months after receiving the injections.

Despite positive phase 2 trial results, Genocea Biosciences, Inc, which developed GEN-003 decided to pull the plug on the vaccine last year. GEN-003 now appears under the “Partnering” section of Genocea’s website and is listed as “a Phase 3-ready investigational immunotherapy for the treatment of genital herpes infections.”