September 2012–Healthy adults who get sick with the flu usually feel better within ten days, although flu can sometimes lead to pneumonia, exacerbation of chronic illnesses, or even death. The disease is caused by a highly contagious virus of which there are three types: A, B, and C. Type C is relatively benign but the other two are responsible for seasonal flu epidemics as well as world-wide pandemics. They mutate rapidly, and thus vaccines must be designed and manufactured annually to address the current strains of virus. This process is expensive, slow, and sometimes unsuccessful. Consequently, there is acute interest in the development of a “universal” flu vaccine that would generate long-lasting immunity to most viruses, thereby eliminating the need for preparation and administration of annual injections.
Biondvax, based in Nes Tziona, Israel, is one of several companies developing such a vaccine. The company was founded in 2003 and has been publicly traded on the Tel Aviv Stock Exchange since 2007 (Ticker: BNDX). Its development of a universal vaccine is based on 20 years of research by Professor Ruth Arnon at the Weizmann Institute in Israel. The technology builds on the fact that a flu virus, whether Type A or B, has components that are conserved regardless of mutations in other portions of the virus. Biondvax’s vaccine contains a proprietary combination of nine conserved viral components common to most influenza strains, and stimulates the body to attack any virus containing these conserved pieces. The company completed a Phase II clinical trial which showed that the vaccine is well tolerated and generates immunity to multiple flu strains without the need for standard seasonal vaccines. This is possible because, if a vaccine is effective, a person develops immunity to its target for many years, whether that target is one or two strains of virus, as is the case for seasonal vaccines, or most of them.
Biondvax’s product might also work to “prime” the body so that annual seasonal vaccines are more effective. This is particularly important for people ages 65 and older, a group that is at higher risk for serious complications and mortality due to flu, but is less likely than the rest of the population to develop immunity from vaccinations. Use of a primer together with a seasonal vaccine could raise the success rate of vaccination in the older population. The company has tested this “primer” application for its product with a separate Phase II trial that included only elderly patients.
In a recent interview, Dr. Tamar Ben-Yedidia, the Chief Scientific Officer, reviewed the results of this trial and explained the evidence that Biondvax’s vaccine exceeded the performance of a seasonal flu vaccine approved by the FDA in 2009 for use in the elderly (Fluzone High Dose, Sanofi Pasteur), suggesting that the vaccine could be able to meet FDA standards in future trials. In the U.S., 90% of deaths associated with influenza occur in those 65 and older so there is a growing demand for a product that will protect them.
Biondvax has had two pre-IND (Investigational New Drug application) meetings with the FDA. The second, held in August, 2012, focused on use of its vaccine as a “primer” in the elderly. The company’s CEO, Dr. Ron Babecoff, said in a recent interview held at company headquarters that information gathered at that meeting will be used to design a phase III trial, and that the company is looking for partners to help it begin this next stage. To date, Biondvax has raised $18 million: $15 million from investors and $3 million in grants from the Israeli government.
Several other companies are also working to commercialize a universal flu vaccine. These include Seek, Dynavax Technologies Corporation, VaxInnate Corporation, and Innovia Pharmaceuticals, Inc. Seek is a privately held company based in the U.K. In June, 2012 it published positive results for its Phase I trial, and has begun the first Phase II trial of its vaccine. It is the only company besides Biondvax to have started Phase II trials. Dynavax, based in Berkeley, California and traded on NASDAQ (Ticker: DVAX), has begun enrolling patients in its first human trial (Phase I) of a universal flu vaccine but has not yet reported results.
VaxInnate and Inovio are working on vaccines to target more than one strain of virus at a time, but their products do not target all Type A and B viruses. A privately held company located in New Jersey, VaxInnate was awarded over $100 million by the U.S. Department of Health and Human Services to work on its vaccines; these are meant for long-term protection against most Type A flu viruses, but do not address Type B. The company began enrollment for its first Phase I clinical trial in June, 2012, and focuses on the vulnerability of the elderly population. Inovio is a San Diego-based company traded on the American Stock Exchange (AMEX:INO). Like Biondvax, it is focusing on a vaccine to be used as a primer in the elderly. However, its product is only designed to work on strains of the H1N1 subtype of Influenza A. The company began its first Phase 1 study in July, 2012.
There are several companies vying to bring a universal vaccine to market, or at least one that targets multiple strains of flu. Biondvax targets both main types of influenza virus, appears to be furthest ahead in clinical trials, and uses innovative technology that makes it possible to produce vaccine on an industrial scale in only 6-8 weeks. This is in stark contrast to production of standard seasonal vaccines which can take 5-7 months. If Biondvax can raise the necessary capital to continue developing its product, it may well produce an important new vaccine for the worldwide market. It will be interesting to see the results of the company’s next clinical trials.
K. Kleinhaus is an Assistant Professor at New York University School of Medicine. She has a particular interest in Israeli innovation in biotechnology and medical devices. Click here to read her full bio.