A new candidate vaccine against hepatitis E, developed collaboratively by GlaxoSmithKline (GSK) and the Walter Reed Army Institute of Research (WRAIR), was found to be 95.5 per cent effective in a phase two trial, according to a study to be published in the New England Journal of Medicine. Hepatitis E, a waterborne strain of hepatitis that occurs almost exclusively in the developing world, is currently without cure or medical prophylaxis.
Three doses were administered over six months. After the third dose and over a follow-up period of approximately 20 months, there was a 7 per cent attack rate in those in the placebo group and a 0.3 per cent rate in those who had received the vaccine. The trial's results also show that the vaccine was well-tolerated, with a safety profile similar to placebo, except for increased pain at the injection site; the most common adverse reaction besides injection site pain was mild to moderate headache after vaccination.
"This research represents a major breakthrough against hepatitis," said Dr Bruce Innis, a co-author of the study and vice president, clinical research and development, GSK Biologicals, the vaccine division of GSK. "Hepatitis E is among the most common causes of jaundice in the developing world and its large, frequent outbreaks have devastating consequences. Today's news that an effective vaccine may have been found means it's time to put the disease on the global agenda and begin thinking about immunization strategies."
"This project extends GSK's long-standing commitment to hepatitis and builds upon our introduction of the world's first recombinant hepatitis B vaccine as well as the first hepatitis A vaccine," added W Ripley Ballou, vice president, emerging diseases, clinical research and development, GSK Biologicals. "This breakthrough reflects the hard work and expertise of our long-time collaborators in hepatitis research. We are actively working to identify new partners to complete the vaccine's development".
GSK will actively look to partner with the public sector to continue the vaccine's development, in keeping with its tradition of public-private partnerships for vaccines addressing the diseases of the developing world, such as malaria, TB and HIV.
Hepatitis E is clinically indistinguishable from other types of acute viral hepatitis. It is especially a problem in developing countries, with outbreaks most common during rainy seasons and in areas with poor sanitation. In India, the lifetime infection risk surpasses 60 per cent, which results in hundreds of thousands of illnesses annually.
Hepatitis E typically has a 40-day incubation period, with the highest attack rates in those 15 to 40 years old. Illness severity increases with age, and the overall case-fatality ratio is estimated to be 1 to 3 per cent. Pregnant women are at greatest risk, and 5 to 25 per cent of those infected during pregnancy die. Survivors have high rates of spontaneous abortion and still birth.
Two thousand volunteers participated in the double-blind, placebo-controlled trial, conducted in accordance with international clinical guidelines and monitored by independent, international review boards.
"GSK involvement dates from 1993. The development of this vaccine is the latest product of GSK's and Walter Reed's more than 20-year history of collaboration to develop vaccines for diseases in the developing world. The promising results of this trial are proof that together we can find the technology to protect those at risk," added Dr Innis.
The vaccine technology was first developed by Genelabs Technologies Inc, which sequenced the hepatitis E genome. Genelabs has granted an exclusive license to GlaxoSmithKline Biologicals for hepatitis E vaccines. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) developed the candidate vaccine used in this and two earlier clinical trials. NIH also established its viability in preclinical studies. Through an agreement with GlaxoSmithKline, Walter Reed led the vaccine's clinical development, in collaboration with scientists and physicians at GlaxoSmithKline, pursuant to an investigational new drug application filed with the supervision of the US Food and Drug Administration and approvals granted by the Nepal Health Research Council.