CAMBRIDGE, Mass.—Genocea Biosciences, Inc., a biopharmaceutical company developing T cell-directed vaccines and immunotherapies, has announced positive top-line data from a Phase 2 dose optimization trial evaluating GEN-003 for the treatment of genital herpes. During the 28-day observation period immediately after completion of dosing, the best dose of 60 µg per protein/75 µg of Matrix-M2TM adjuvant demonstrated a highly statistically significant (p<0.0001) 55 percent reduction from baseline in the viral shedding rate, the primary endpoint of the trial and a measure of anti-viral activity. All dose combinations tested, including the successful 30 µg per protein/50 µg of adjuvant dose from the prior Phase 1/2a trial, demonstrated a statistically significant viral shedding rate reduction versus baseline and only the lowest dose combination did not demonstrate a statistically significant reduction versus placebo.
“The dormant genital herpes virus rests near the spinal cord,” notes Dr. Seth Hetherington, Genocea’s chief medical officer. “Individuals who have active genital herpes shed virus intermittently even without lesions. When active the virus can be transmitted. To measure viral shedding, a swab is used twice a day for 28 days. PCR is used to detect the virus.”
In a planned secondary analysis to assess impact on patient-reported genital lesion rates, a self-assessed measurement of clinical disease, all dose groups, including the placebo group, demonstrated a statistically significant reduction from baseline. Hetherington points out that the assessment of genital lesions is subjective and that the placebo group was small (1/7 of 310) and results may have been influenced by random chance.
Referring to the study as a “Wild success,” Chip Clark, Genocea president and chief executive officer added “We are extremely pleased with these positive top-line results which have successfully allowed us to identify the optimal dose to advance into further trials. The results strengthen the product profile from our Phase 1/2a trial, which we have shown in market research to be highly clinically meaningful and commercially attractive, providing further evidence of the strong value proposition of GEN-003 for patients, physicians and payers.”
The Phase 2 study showed that GEN-003 was generally safe and well tolerated by patients, with no serious adverse events related to the vaccine. Safety data throughout the trial is monitored by an independent data safety monitoring board. Although reactogenicity increased with adjuvant dose, there was no difference in discontinuations in patient dosing due to adverse events across the different treatment arms.
“People living with genital herpes are seeking treatments that deliver on efficacy and provide them with peace of mind that they are at less risk of transmitting the infection to their sexual partners,” said Peter Leone, M.D., professor of Medicine and adjunct professor of epidemiology at the University of North Carolina, and an investigator in the GEN-003 dose optimization trial. “We know that asymptomatic viral shedding is the driver of herpes transmission and GEN-003’s demonstrated antiviral efficacy data reported to date suggest this immunotherapy can be an effective future treatment.”
The Phase 2 study enrolled 310 subjects from 17 institutions in the United States. Subjects were randomized to one of six dosing groups of either 30 µg or 60 µg per protein paired with one of three adjuvant doses (25 µg, 50 µg, or 75 µg). A seventh group received placebo. Subjects received three doses of GEN-003 or placebo at 21-day intervals. Baseline viral shedding and genital lesion rates were established for each subject in a 28-day observation period prior to the commencement of dosing by collecting 56 genital swab samples (two per day), which were analyzed for the presence of HSV-2 DNA, and by recording the days on which genital lesions were present. This 28-day observation period was repeated immediately after the completion of dosing and will be repeated two more times over the course of this trial, at six and twelve months following dosing. No booster doses will be given.
A prior Phase 1/2a clinical trial demonstrated, at the corresponding immediate post dosing 28-day observation period, a highly statistically significant 52 percent reduction in the viral shedding rate and a highly statistically significant 48 percent reduction in the genital lesion rate compared to baseline at a dose of 30 µg per protein/50 µg of Matrix-M2 adjuvant.
Inducing a T cell response against HSV-2 is critical to treating the clinical symptoms of disease and controlling transmission of the infection. GEN-003 is a first-in-class T cell directed immunotherapy designed to elicit both a T cell and B cell (antibody) immune response. The immunotherapy was designed using Genocea’s ATLAS™ platform, which profiles the comprehensive spectrum of actual T cell responses mounted by humans in response to disease, to identify antigen targets that drive T cell response. GEN-003 includes the antigens ICP4 and gD2 along with Matrix-M2 adjuvant, which Genocea licensed from Novavax, Inc.
Genital Herpes affects more than 400 million people worldwide and causes recurrent, painful genital lesions. It can be transmitted to sexual partners, even when the disease is asymptomatic. Current genital herpes therapies only partially control clinical symptoms and viral shedding, a process which drives disease transmission. Incomplete control of genital lesions and transmission risk, expense and the perceived inconvenience of taking a daily medication are hurdles for long-term disease management. Immunity through T cells is believed to be particularly critical to the control and possible prevention of genital herpes infections.
T cells are increasingly recognized as a critical element of protective immune responses to a wide range of diseases, but traditional discovery methods have proven unable to identify the targets of such protective immune response. Using ATLAS™, its proprietary technology platform, Genocea identifies these targets to potentially enable the rapid development of medicines to address critical patient needs. Genocea's pipeline of novel clinical stage T cell-enabled product candidates includes GEN-003 for genital herpes, GEN-004 for the prevention of infection by all serotypes of pneumococcus, and earlier-stage programs in chlamydia, genital herpes prophylaxis, malaria and cancer immunotherapy.