CMV
View TransVax™ CMV Vaccine Phase 2 Interim Efficacy Results
In 2003, we announced our first independent product development program focused on infectious diseases, a DNA-based immunotherapeutic vaccine against CMV. Our CMV vaccine is intended to induce both cellular and antibody immune responses against the target pathogen without the safety concerns that live-attenuated virus vaccines pose for immunocompromised patients. Currently, there is no approved vaccine for CMV.
The Institute of Medicine of the National Academy of Sciences estimated the cost of treating the consequences of CMV infection in the United States at more than $4 billion per year in a 1999 report, and placed the need for a CMV vaccine in its first priority category on the basis of cost-effectiveness. Furthermore, the National Vaccine Advisory Committee in 2004 agreed that increased research support by the NIH, CDC and vaccine manufacturers is critical for developing an effective CMV vaccine that prevents death, deafness, and central nervous system injury due to congenital CMV infection. Our initial focus is on the transplantation indication, which we believe, if successful, should allow proof-of-concept that could then lead to the opportunity to develop a CMV vaccine for other groups, such as at-risk women of reproductive age.
Our CMV vaccine product development program is based on:
- CMV genes that encode two immunogenic proteins, glycoprotein B and phosphoprotein 65, which are associated with protective antibody and cellular immune responses; and
- Our DNA vaccine technologies that have the ability to induce cellular immune responses and trigger production of antibodies without the safety concerns that conventional attenuated vaccines have posed for immunocompromised patient
We initiated a Phase 1 clinical trial of our CMV vaccine in 2004. Subjects in the trial were healthy adults that were monitored primarily for safety, with secondary endpoints of immunogenicity. The trial tested two dosing levels and two dosing schedules, with approximately half of the subjects in the trial having prior exposure to CMV (referred to as seropositive) and half with no evidence of prior exposure (referred to as seronegative). Results from the Phase 1 trial indicated that our CMV vaccine was safe and well-tolerated by a majority of subjects, with temporary injection site pain being the most common side effect. The vaccine induced antibody and T-cell immune responses at both dose levels and both dosing schedules tested.
Based on these results, we designed a Phase 2 study in hematopoietic cell transplant, or HCT, patients which opened for enrollment in 2006. Our Phase 2 CMV trial is a placebo-controlled randomized study which calls for enrollment of 80 related donor and recipient pairs. Patients are randomized on a 1:1 basis. The primary endpoints are safety and the occurrence rate of clinically significant viremia. In 2007, we implemented a trial protocol amendment designed to increase enrollment rates. This amendment allows vaccination of only the recipients in hematopoietic cell transplants from unrelated donors. This expansion has opened our trial to a much larger pool of patients who have constituted a significant majority of our new enrollments. As a result, we have made the decision to phase out the original paired donor-recipient arm and will continue the study with the recipient-only arm.
In October 2007, an independent safety monitoring board found no safety issues and recommended continuation of the Phase 2 trial. The interim safety evaluation was completed after two-month follow-up visits for the first 20 transplant recipients enrolled in the study. We announced in November 2008 that we had completed enrollment of subjects in our Phase 2 trial. An interim analysis of immunogenicity data for the first 33 transplant recipients in the recipient-only arm of the study showed significant (p<0.05) post-transplant enhancement of CMV-specific T-cell responses in subjects receiving vaccine compared with subjects receiving placebo.
In 2005, the Office of Orphan Products Development of the U.S. Food and Drug Administration, or FDA, designated our vaccine against CMV as an orphan drug for the prevention of clinically significant CMV viremia, CMV disease and associated complications in at-risk HCT and solid organ transplant populations. Orphan drug designation provides certain tax benefits for qualifying expenses and can result in extended marketing exclusivity. In addition, we have been awarded approximately $4.1 million for research and development related to our CMV vaccine program under three grants from the National Institute of Allergy and Infectious Diseases, or NIAID, of the NIH.
In 2008, we licensed from The Wistar Institute exclusive, worldwide rights to Wistar’s Towne strain of CMV and related technologies. The Towne strain is an attenuated, or weakened, form of human CMV which was developed for potential vaccine applications by vaccinologist Stanley Plotkin, M.D., a member of Wistar’s research faculty from 1960 to 1991 and co-author of the definitive medical text “Vaccines.”
About CMV
CMV is a herpes virus that infects more than half of all adults in the United States by age 40, and is even more widespread in developing countries. While a healthy immune system typically protects an infected person against CMV disease, it rarely succeeds in completely eliminating the infection, and those whose immune systems are not fully functional are at high risk of CMV reactivation, potentially leading to severe illness or death. These include transplant patients who take immunosuppressive drugs, AIDS patients, and fetuses and newborns of mothers who first become infected during pregnancy.
The Institute of Medicine of the National Academy of Sciences estimated the cost of treating the consequences of CMV infection in the United States at more than $4 billion per year in a 1999 report, and placed the need for a CMV vaccine in its first priority category on the basis of cost-effectiveness. Furthermore, the National Vaccine Advisory Committee in 2004 agreed that increased research support by the NIH, CDC and vaccine manufacturers is critical for developing an effective CMV vaccine that prevents death, deafness, and central nervous system injury due to congenital CMV infection.
Approximately 50% to 60% of transplant patients in the United States annually will develop clinical CMV disease. Transplant patients who develop CMV disease use significantly more healthcare resources, including longer hospitalization, than asymptomatic or uninfected transplant patients. Anti-CMV immune globulin and relatively toxic antiviral drug therapy are used to control the disease, but do not fully prevent or eliminate the infection. As a result, many patients require long-term maintenance therapy, and reactivation of the disease often occurs if drug therapy is discontinued or if drug resistance develops. The treatment itself can be costly and, in some forms, inconvenient. Treatment is not effective for all patients and side effects may be severe, including damage to the bone marrow or kidneys.
According to the CDC, CMV is the most common virus transmitted to a pregnant woman’s unborn child. In the United States, approximately 1% to 4% of uninfected mothers develop primary CMV infection during pregnancy. Women who become infected with CMV during pregnancy pass the virus to their unborn children 33% of the time. Congenital CMV is as common a cause of serious disability as Down syndrome, fetal alcohol syndrome, and neural tube defects. Approximately 8,000 children each year suffer permanent disabilities caused by CMV. The substantial costs associated with congenital CMV are related to the lifelong disabilities associated with symptomatic infection, since patients require lifelong residential care and medical intervention.