For Dennis Carson, however, the FDA announcement represented the culmination of a scientific odyssey that took 21 years. To him, vaccines represent a paradigm in preventive health—even though vaccines take longer to develop and typically don’t bring the kind of financial payoffs that blockbuster drugs yield in the life sciences industry.
Carson, a 71-year-old professor emeritus at the UC San Diego School of Medicine, co-founded Dynavax in 1996 with the idea of developing a new hepatitis B vaccine based on short bacterial DNA sequences. The intended result would provoke a stronger and longer-lasting immune response, and Carson says that has been borne out. It may have been a long slog to win FDA approval, but “It hasn’t been a long slog because the science was wrong,” he said.
The recombinant vaccine, known commercially as Heplisav-B, is the first Dynavax product to win FDA approval, and the first new hepatitis B vaccine in the United States in more than 25 years.
The underlying idea, based on research led by Carson and UC San Diego’s Eyal Raz, is that “immunostimulatory DNA,” serving as the adjuvant in recombinant biologic vaccines, would be a kind of interchangeable part in an array of new vaccines. The idea is only now coming into its own. Carson, who still operates a lab at the Sanford Consortium for Regenerative Medicine, says similar DNA sequences could some day be used in other vaccines to stimulate an immune response to tuberculosis, malaria, flu, and even cancer.
Dynavax is now conducting trials of cancer vaccines based on immunostimulatory DNA oligonucleotides. The selected agents are injected directly into the tumors (for melanoma and head and neck cancers), or given by inhalation (in lung cancer).
Getting this far in hepatitis B, though, has required the patience of Job.
As a point of comparison, it took 13 years to win FDA approval for the chemotherapy drug 2-CdA (Cladribine), which Carson helped develop with Ernest Beutler, his mentor at The Scripps Research Institute. Yet in his office, which overlooks the Torrey Pines Golf Course and the Pacific Ocean, Carson takes a serene view.
“Twenty [plus] years sounds like a long time,” he said. “But for a vaccine that is given to a lot of people, and where safety is the prime issue, it takes a long time.”
Dynavax initially submitted its application for Heplisav-B in 2012. A few of the recipients in clinical trials had developed autoimmune diseases and cardiac events, so the FDA asked Dynavax to conduct an additional clinical trial in 2013 to determine if these events were related to the vaccine or just random. The FDA sought more information and analyses again in 2016.
Only large-scale studies could provide a definitive answer, and the company says its Heplisav-B studies included 10,038 patients altogether. According to Carson, an FDA advisory committee concluded that the adverse reactions were no more than could be expected by chance. Nontheless, they asked that Dynavax conduct post-marketing vigilance studies.
Dynavax plans to introduce Heplisav-B as its first commercial product in early 2018. The company managed to sustain itself initially through the support of individual investors and research grants from the National Institutes of Health. The company went public in 2004. “It’s wonderful in the United States that investors will keep pouring money into a company to keep it going,” Carson said.
There is no cure for hepatitis B, an extremely infectious virus that causes serious liver disease. While most people recover, about 15 percent of the cases become chronic—and can lead to liver cirrhosis and even cancer. Dynavax says results from one of its clinical trials (with 6,665 participants) showed that its Heplisav-B vaccine provided a higher rate of protection—95 percent versus 81 percent for Engerix-B, the current standard vaccine marketed by GlaxoSmithKline (NYSE: GSK).
In a Nov. 9 conference call with analysts and investors, Dynavax CEO Eddie Gray proclaimed, “This is a great day for our company, for our investors, and also I think for public health.”
Dynavax offers a dosing schedule that some patients may find preferable. The company says its vaccine provides full immunity with two injections over four weeks, compared to Engerix-B, which requires more injections over several months. The goal at Dynavax, Gray said on the conference call, is to make Heplisav-B “the adult hepatitis B vaccine of choice in the United States,” a market that Dynavax estimates at $270 million a year—and growing. In 2012, an advisory committee on immunization practices recommended that the list of population at risk for hepatitis B, and who should be vaccinated, should include people with diabetes.
Despite all that, Carson said, “You do not see a lot of biotechs doing vaccines, because of the longer development time and cost.” The incentives to develop vaccines also are lower, because they are hard to manufacture and generally only administered once.
“Vaccines are miracle drugs, along with antibiotics, in terms of extending our lifespans,” Carson said. “In terms of human health, there’s nothing like them. But they’re not tremendous money-makers because you don’t need to take them every day.”
Colorized electron micrograph image of hepatitis b particles via Wikipedia by Dr. Erskine Palmer / CDC.