Belgian biotech Innogenetics today announced promising findings in a study of their hepatitis C therapeutic vaccine. Out of 23 study participants with chronic hepatitis C who had received multiple courses of the vaccine, 10 showed improvements in liver fibrosis in the three years since initial vaccination. Another 10 had stable fibrosis. Overall, fibrosis regressed by 0.43 points on the Ishak scale, which stages fibrosis on a scale from 0 (no fibrosis) to 6 (cirrhosis).
Therapeutic vaccines are vaccines that don't prevent an infection, but help people already infected to mount a stronger immune response to their infection. The Innogenetics vaccine is based on a purified version of E1, one of hepatitis C's two envelope proteins (proteins that coat the envelope of the virus and bind to target cells -- i.e. liver cells). In theory, the vaccine would help keep hepatitis C under control by boosting the ability of the immune system to target the virus, preventing further liver damage.
An effective therapeutic vaccine for hepatitis C would be a major advance in therapy. Such a vaccine could delay the need for treatment with interferon and ribavirin, and help people who do not respond to current treatment (most of the Innogenetics study participants are people who did not respond to interferon-based therapy). But therapeutic vaccines are in some ways more difficult to develop than traditional preventative vaccines. Dozens of companies are working on therapeutic vaccines for a variety of conditions, most notably cancer, but also infectious diseases like hepatitis C, hepatitis B, and HIV. So far, no therapeutic vaccines have been approved to treat any of these conditions.
(For a good, readable survey of therapeutic vaccine development in HIV, see this recent article by Simon Noble from the International AIDS Vaccine Initiative [IAVI]. See also this review of therapeutic vaccines for infectious diseases [abstract; email me for the full article] from the journal Current Opinion in Microbiology.)
So does the Innogenetics vaccine really work? Here are some caveats:
- So far we only have a press release. It's hard to evaluate the data fully until it comes out in a reputable, peer-reviewed journal.
- The reduction in fibrosis score is impressive, but relatively small and could in theory be due to chance. In a commentary on earlier data from this study published in Hepatology (Nevens et al., abstract here), Marc Ghany and David Kleiner of the National Institutes of Health discussed the challenges of evaluating improvement in fibrosis, noting another study showing that 20% of people who do not receive any treatment (or therapeutic vaccination) showed a regression of fibrosis by a full point on the Ishak scale over an average interval of 44 months (commentary in Hepatology here [email me if you want the PDF], abstract for cited study from Gastroenterology here). So it's possible that the observed reversion in fibrosis could be a statistical fluke, especially given the limitations of liver biopsies (sampling error, intraobserver variation) discussed in the previous post. It's also possible that if the vaccine makes a difference, it will take longer (5-10 years) to really show the impact.
- If the Innogenetics therapeutic vaccine works, you'd expect to see a reduction in hepatitis C viral load, since the immune system would presumably be controlling the virus better. With this vaccine, that doesn't seem to happen, raising the question of how it might actually be working to reduce fibrosis.
- There were only 23 study participants described in the press release, all of whom received vaccinations. A true demonstration of effectiveness would require a comparison group who did not receive the vaccine. Innogenetics is currently conducting a larger study of 164 people with hepatitis C, where some participants receive vaccinations and some receive placebo.
The study described in the press release is considered a phase 2a study -- drug development proceeds through 3 phases before a drug (or vaccine) will be considered for approval. It will take several years to demonstrate whether Innogenetics' therapeutic vaccine works to the satisfaction of regulatory bodies (e.g., the Food and Drugs Administration [FDA]). In the meantime, studies are on-going in Europe.
The take-home message? This news offers some hope, but real science isn't advanced by press releases. And even the most encouraging preliminary results often don't end up panning out. To quote from the title of Ghany and Kleiner's commentary, "all that glitters is not gold."
But keep in mind that other companies, like Chiron and Austria's Intercell, are also trying to develop therapeutic vaccines for hepatitis C. Sooner or later, someone's going to get it right.