Vical Targets Development of Novel Cytomegalovirus Vaccine

SAN DIEGO -- Vical Incorporated announced today that a DNA-based vaccine against cytomegalovirus (CMV) will be its first independent development program focused on infectious diseases.

Currently, there is no approved vaccine or even a late-stage vaccine development program for CMV. Vical intends to begin human Phase I clinical testing of the vaccine by year-end 2003 for an initial indication in humans at greatest risk of serious complications from CMV infection -- patients undergoing bone marrow or solid organ transplantation.

Future development could lead to a vaccine for other high-risk groups such as immunocompromised individuals and women of reproductive age, and eventually to a universal vaccine for pediatric use. The Institute of Medicine (IOM) of the National Academy of Sciences has estimated the cost of treating the consequences of CMV infection in the United States at more than $4 billion per year and placed a CMV vaccine in its first priority category on the basis of cost-effectiveness(1).

"A vaccine to protect against CMV disease offers Vical a compelling market opportunity consistent with our product development strategy," said Vical's president and CEO, Vijay Samant. "Our initial focus on the transplantation indication should allow straightforward, early proof-of-concept that could then lead to a larger downstream commercial opportunity. The unmet medical need in pregnant women at-risk for CMV infection and the need for controlling viral transmission in the general population may allow substantial product expansion in the years ahead. Success in our first independent vaccine programs with our patented technology platforms would pave the way for development of additional vaccines against other infectious diseases."

When asked to comment on CMV, Stanley A. Plotkin, MD, renowned vaccinologist, professor emeritus at the University of Pennsylvania and co-author of the definitive medical text Vaccines, said, "This is an important vaccine target, and the development of an effective vaccine for transplant patients would have important implications for the protection of pregnant women against CMV."

Plotkin has written, "CMV has been called the 'troll of transplantation' because it complicates the post-operative graft period with febrile illness that enhances rejection, thus exacting a toll, as did the trolls of Norse legend. For pediatricians, CMV is analogous to demons in ancient Teutonic mythology, who would steal healthy newborn babies from their cradles and replace them with damaged infants of their own."

Vical's Chief Scientific Officer David C. Kaslow, MD, says the CMV immunotherapeutic vaccine program is based on:

-- CMV genes that encode highly immunogenic proteins associated with

protective antibody and cellular immune responses;

-- Vical's DNA vaccine technologies that have the ability to induce

potent cellular immune responses against target pathogens as well as

to trigger production of antibodies without the safety concerns that

conventional attenuated vaccines have posed for immunocompromised

patients; and

-- a focused clinical development plan that will allow us to quickly

establish proof of efficacy in transplant patients.

CMV is a herpes virus, part of the family of viruses that cause genital herpes, cold sores or fever blisters, chicken pox and infectious mononucleosis. Although the body has difficulties in completely ridding itself of CMV, a healthy immune system usually is able to control the virus in check, often for the life of the individual. As a result, CMV disease rarely recurs in healthy individuals, and reactivation typically occurs only when the immune system is compromised by other disease or drugs. People at greatest risk include bone marrow and solid organ transplant patients who take immunosuppressive drugs, AIDS patients and other immunocompromised individuals, and fetuses and newborns of mothers who become infected during pregnancy.

CMV infection affects an estimated 30 to 60 percent of bone marrow transplant or organ transplant recipients, causing transplant rejection, serious illness and even death if untreated. Transplant patients who develop CMV disease use significantly more health care resources, including longer hospitalization and more intensive care unit stays, than asymptomatic or uninfected transplant patients. Expensive antiviral drug therapy is used to control the disease, but it does not 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 bone marrow or kidneys.

The disease is spread by exposure to any bodily fluid of an infected person. Transmission can occur through sexual contact, through breast milk, through organ transplants, and occasionally through blood transfusions. Close contact with others, as in a family or day care setting, can allow the virus to pass from bodily fluids of an infected person to the hands and then to the nose or mouth of an uninfected person. The U.S. Centers for Disease Control and Prevention estimates that, in the United States, CMV infects more than half of all adults by age 40, and as many as 85 percent at some point in their lives. An estimated 25,000 patients receive solid organ transplants in the United States annually, and another 4,000 receive bone marrow transplants, with similar numbers in the European market. Approximately one in a hundred infants in the United States is born with CMV infection, leading to severe consequences in about 3,600 infants and death in about 400 infants per year. Nearly 3,000 immunocompromised patients suffer from CMV infection in the United States each year, causing severe consequences in more than half and death in more than 150 cases.

(1) Institute of Medicine. Vaccines for the 21st Century: A Tool for

Decisionmaking. Washington, DC: National Academy Press, 1999.

Source: Vical Incorporated