Bioterror: VaxGen stops work on anthrax vaccine; smallpox contract awarded

A few recent items about efforts to develop vaccines against possible agents of bioterrorism:

-- We've been following the saga of the VaxGen anthrax vaccine contract since beginning this site in March 2006 (complete coverage here). When we last checked in -- in January -- the news was that HHS had finally canceled the $877.5 million contract awarded to VaxGen as part of Project Bioshield. Just before Memorial Day weekend (likely deliberately timed to reduce media coverage), VaxGen announced that is was ceasing further development of the vaccine, an all-but-inevitable development without new funding.

Here's the VaxGen press release and a story from CIDRAP News. The press release notes that VaxGen will be laying off 20 employees as a result of this decision, which, amazingly, accounts for 25% of its workforce. There's little doubt that this point will be noted by those who had long criticized the decision to award such a significant contract to a very small, unproven player in vaccine development.

Even more bad news is highlighted in this CQ.com story, which notes the new hurdles VaxGen faces is selling its anthrax vaccine technology developed thus far.

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-- Speaking of CQ.com and bioterror vaccines, following up on this previous post, the anticipated agreement between HHS and Bavarian Nordic for a second-generation smallpox vaccine was completed last week. Here's the HHS press release and an AP story, courtesy of CBSNews.com.

Potency concerns for pandemic flu vaccine stockpiles; HHS planning update; more contracts awarded

For months, we've been discussing some of the many challenges and potential problems associated with the "pre-pandemic" avian flu vaccines currently being developed, tested, and stockpiled. More reason for concern came late last week, when this CIDRAP News story reported that a significant percentage of the stockpile has lost potency, resulting in a one-million-person decrease in the number of people who could potentially be protected by vaccine doses currently on hand (3 million, down from 4 million in an HHS document released in July). Here's an excerpt from the story, quoting an HHS spokesman:

"'All vaccines have shelf lives,' Hall told CIDRAP News. 'The early vaccine that was purchased, the first lots, have begun to lose their potency.'

He said the potency has begun to decrease for 'the majority' of doses in the stockpile, adding, 'That doesn't mean it goes from 100 percent to zero percent' or that the doses would be unusable."

On Friday, a day after the story above appeared, the same HHS spokesman seemed to walk back his earlier comments in this CIDRAP follow-up, explaining that only 20% of the current doses on hand are losing potency, not "a majority," as he previously said. Either way, it should come as a surprise to no one that these vaccines have a limited shelf life, an issue avoided by seasonal flu vaccines on account of their annual reformulations. Even with full potency, the vaccine doses in question are from "clade 1" virus samples from 2004. Since early this year, vaccine development has been based on a 2005 sample, working toward "clade 2" vaccines expected to be a closer fit to a possible pandemic strain.

All of this news came as a result of the release last week of the latest HHS Pandemic Planning Update. Not a lot of news in the 13-page report (and, thus, virtually no news coverage about its release), but it provides a good overview of the current status of U.S. planning and spending.

Finally, HHS announced today that another $200 million in contracts have been awarded to Sanofi Pasteur, Novartis, and GlaxoSmithKline for an additional 5.3 million doses of "clade 2" pre-pandemic vaccines, enough to vaccinate roughly 2.7 million people. (Here's the story from Reuters.) This would double the current stockpile (notwithstanding further decreases in potency of older vaccines), but still represent only a bit more than 1/4 of the goal of having enough vaccine stockpiled for 20 million Americans.

Novartis to build first U.S. cell-culture flu vaccine plant

Using $220 million awarded in May by HHS as part of the government's pandemic flu plan, Novartis announced plans yesterday to build the first U.S. manufacturing plant for cell-culture derived flu vaccines. The plant, to be built in Holly Springs, NC, has a total bill of $600 million, according to this Novartis press release. Here is a news report on the announcement from Reuters and a lengthier story from the U. of Minnesota's CIDRAP.

Once complete, the plant will be able to produce 50 million doses of seasonal flu vaccine annually and as many as 150 million doses of a possible pandemic flu vaccine. It marks another step away from reliance on an egg-based flu vaccine production method, with its many shortcomings. We'll still be using eggs for many years to come, however. Novartis estimates the plant won't be fully functional until 2012.

HHS Update on Avian Flu Preparations

HHS Secretary Michael Leavitt released an update today on U.S. preparations for a potential pandemic. The PDF is available here. After a sobering (but accurate) introduction assessing the current status of the virus and its westward spread, vaccines receive significant attention in the report.

One interesting piece of information appears in the pie chart on page 2 showing funding allocations. It notes that HHS was appropriated $3.3 billion for pandemic flu activities during the current fiscal year. Of that amount, nearly $1.8 billion (54%) has been allocated to vaccines. That’s more than the amount given to antivirals, state and local preparedness, medical supplies, surveillance, lab capacity, risk communications, and international activities combined. Look for comments in the next few days from constituencies in the medical community expressing concern over this distribution of resources, particularly among state and local public health officials.

Of the 12-page document, nearly 3.5 are devoted to vaccines. It appears to be a thorough, honest assessment of where we are regarding vaccine development and the many unknowns moving forward (which we’ve discussed previously here and here).

One statement in the report, while not new, should remind us of the many ethical issues regarding vaccine safety, manufacturer liability and the limits thereof, and the potential consequences of large-scale immunization efforts that could surface in a worst-case scenario…

“If a pandemic occurs prior to licensure of a vaccine, the FDA can use its Emergency Use Authorization authority to permit the use of unapproved products (or to permit unapproved uses for previously approved products) if there’s a reasonable belief the products may be effective and if the benefits would outweigh risks.”

More to come, no doubt.

NIH/CDC working on 2nd avian flu vaccine

At the National Immunization Conference in Atlanta, HHS secretary Michael Leavitt announced today that the development of a second avian flu vaccine has begun, this one on a more recent isolate of the virus. CBSNews.com has the story.

The 'original' vaccine is based on a 2004 sample of avian flu from Vietnam. The U.S. government has already spent $250 million for 8 million doses through contracts with Sanofi Pasteur and Chiron, the story notes. The cycle of vaccine development announced today involves a 2005 isolate from Indonesia. As we've written previously, the question no one can answer is how effective (if at all) earlier vaccines will be against the eventual 'pandemic' strain of avian flu, whenever (or if ever) it arrives.

Ultimately, there's agreement in the scientific community that the only vaccine sure to be effective against a pandemic strain is one developed only after it arrives, requiring a minimum 6-month wait for any vaccine and all but certain supply shortages. At this point, the hope is that these vaccines currently in production will provide some measure of protection in the meantime, if necessary.

The question for public health experts and health economists is whether a semi-annual, $250 million payout for vaccines that may or may not be effective is a sound use of resources as part of preparations for a pandemic. For bioethicists, in addition to the host of issues relating to the allocation of scarce resources, etc., this announcement adds a new wrinkle to consider: If/when a pandemic arrives, it's now possible that several 'generations' of vaccine will be available, with newer generations progressively more effective against the virus than earlier ones. How should this be handled? A national triage system? A roll of the dice based on which manufacturer your physician/hospital/state purchases vaccine from?