Hep B Blog

Monthly Archives: November 2012

Hepatitis B Prevention, Living with Hepatitis B

Personal Reflection on Yesterday’s FDA Vaccine Advisory Panel Review of Dynavax’s New HBV Vaccine

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I was fortunate to have the opportunity to represent the Hepatitis B Foundation at yesterday’s FDA vaccine advisory panel review of Dynavax’s new HEPLISAV vaccine for hepatitis B.  I was there for the public comment period on the second day of the meeting with my prepared statement. I was surprised to find I was the only one there for public comment. Since I’ve never been to anything like this, I don’t know if that is typical or not.  I think my personal story with HBV, and the message from the HBF was important for the FDA panel to hear, so they were sure to be reminded that there are real people affected by chronic hepatitis B.

There has been a great deal of good press about the new Dynavax vaccine. In studies it has superior immunogenicity when compared to the currently available vaccines. Immunity is generated in 2 doses given one month apart, versus the currently available vaccines where it is a three shot series over 6 months. This is particularly important to subpopulations such as those undergoing dialysis, and diabetic adults who are encouraged to be vaccinated against hepatitis B – a new recommendation by the CDC this year. It is also important to the general adult population, where it is found that 30-50% of adults may not complete the 3 shot HBV vaccine series making them vulnerable to infection. This  need for HBV prevention via a more effective vaccine, particularly in needy subpopulations was what was stressed in HBF’s public statement.

I do believe the panel was well aware of the importance of HBV prevention and one doctor made mention of the importance based on “the public comment”, so they were listening. Another doctor mentioned the burden of the disease not only globally, but also in the US. That is often understated.

The FDA panel met both Wednesday and Thursday. The public comment period was Thursday, and I remained there for the vote on two vital questions.  The first question was about whether the immunogenicity data was adequate to support the effectiveness of HEPLISAV for the prevention of hepatitis B infection in adults 18 through 70 years of age? The vote cast showed unanimous agreement in the efficacy of the vaccine.

The other question was about whether the data was adequate to support the safety of HEPLISAV when administered to adults 18 through 70 years. Five members said “yes”, 1 abstained and 8 voted “no”.

Prior to both votes there was a great deal of discussion amongst the panelists, and the representative from Dynavax who responded directly to questions.

Ultimately it came down to a few key points.  It was clear that the panel was impressed with efficacy or level of immunity generated by this new, 2 shot series. This vaccine uses a unique adjuvant. An adjuvant is a substance that is added to the vaccine in order to increase the body’s immune response to the vaccine.  In this case it was a nucleic acid versus a lipid – details of which I do not even pretend to understand. Although this new adjuvant was exciting based on the great immunogenicity data presented by Dynavax, it was also a source of concern because the panel was not sure if there was enough study data that represented all demographics. In other words, this vaccine performed really well, but they weren’t sure if it had been proven safe in different ethnic groups such as African Americans, Asian-Americans, and Hispanics. Since the US is a melting pot, this is important.

The other concern was that the vaccine had not been administered along with other vaccines. Because this vaccine is to be given to adults, they felt it was important that it could be given when an adult came in for their annual flu shot, or another immunization. Adults just don’t get to the doctor’s office that often! Although this was clearly of interest, it was not a deal breaker like the lack of safety data among all demographics. There was the suggestion to introduce the vaccine into the current sub-populations that were in particular need, but not much discussion beyond.

The votes were cast and the panel and the audience dispersed. Looks like Dynavax will need to complete further studies before the vaccine is once again reviewed by the FDA panel for approval. Personally, I believe there’s a real  need and a place for this vaccine, but of course safety always comes first.

Liver Cancer, Living with Hepatitis B

More on Metformin and Statins: Drugs Approved by the FDA for Other Purposes That May Prevent Liver Cancer

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From HBF’s expert Guest Blogger, Dr. Thomas London…

In an earlier blog, I pointed out that the available drugs to treat or prevent primary liver cancer (hepatocellular carcinoma, HCC) have been disappointing.  I noted that there may be drugs used for other purposes that may work against HCC.  The most promising of these was an old drug called metformin that has been used to treat type II diabetes for 17 years.  Now a new study on metformin provides the most intriguing results yet.

At the 2012 Digestive Disease Week meeting in San Diego, an enormous study from Taiwan was reported that encompassed almost all of Taiwan’s 23 million people. (I am indebted to Christine Frangou for her excellent report in Gastroenterology and Endoscopy News and have quoted from it extensively.) The investigators used the Taiwan National Insurance Database to identify all cases of HCC diagnosed from 1997 to 2008. There were 97,430 patients with HCC (most of whom would have had chronic hepatitis B). They were compared with 200,000 controls matched to the HCC cases by age, gender, and date of first physician visit.  Using the same database they linked all patients with diabetes and their treatment methods to patients with and without HCC.

From this they were able to show that patients with diabetes had a 2.3-fold increased risk of developing HCC.  In those patients who were taking metformin, however, HCC occurred about 20% less often than in those who were not treated with metformin. Furthermore, the longer patients took metformin, the lower their risk of HCC; about 7% lower for each year that they took the drug.

This study is not the final answer.  We don’t know why some diabetic patients were treated with metformin and some were not.  It is possible that the patients who did not take metformin had some unknown liver abnormality and were deliberately not treated with metformin.  Nevertheless, anti-tumor effects of metformin in experimental animals and in cell culture systems continue to be reported.  I will keep my eye out for more research on metformin and HCC and report it as it hits the medical press.

Statins are another group of drugs that are in common use. They were first approved by the FDA in 1987 to lower serum cholesterol levels and thereby prevent heart disease.  Statins inhibit an enzyme in the liver used to make cholesterol.  Several isolated reports suggested that statins might also help prevent HCC.  This month investigators at the Mayo Clinic in Rochester, Minnesota reported a meta-analysis (a statistical method to combine results from different studies) of all the reports in the medical literature of new cases (incidence) of HCC and exposure to statin therapy.  Ten studies reporting a total of 4,928 HCC cases in 1,459,417 patients were analyzed.  Overall, patients who were treated with statins had a 40% lower risk of developing HCC than those who were untreated.  The results varied from population to population. Asian populations which were more likely to also have chronic hepatitis B, had a 50% lower risk of developing HCC, while western populations had about a 30% lower risk.

At this time we do not know what the mechanism of a preventative effect of statins on HCC might be.  Nor do we know whether statins might have been withheld from patients with high cholesterol levels because they had a liver abnormality. It is likely, however, that more information on these issues will become available in the near future.  When that happens I will report it to you.

 

Baruch S. Blumberg Institute