Pfizer's Breakthrough Vaccine Could Be A Victim Of Its Own Success

Yesterday morning at a conference on infectious disease in Hyderabad, India, Marc Bonten, an epidemiologist from Utrecht University, the Netherlands, presented results from a giant and innovative study Pfizer conducted of its vaccine, Prevnar 13, in adults over 65. In 84,496 Dutch patients over the age of 65, those who got a Prevnar 13 shot were 45.6% less likely to get serious pneumonia caused by the bacteria strains covered by Prevnar 13 than those who received a placebo shot. “Now, for the first time we know that a vaccine can prevent pneumonia in the elderly,” Bonten told me via phone.

That’s a huge result. Although the vaccine is approved in the U.S. to be given to adults, and although there is a competing, but very different, vaccine from Merck that has been available for decades, success was not a foregone conclusion. And the addressable market is huge. There are 60 million Americans over the age of 65.

But Pfizer, the marketing behemoth that brought the world Lipitor and Viagra, may not be able to reach many of those patients. That’s partly because whether insurers pay for vaccines in the U.S. depends  on the recommendation of the Advisory Committee on Immunization Practices, which is run by the Centers for Disease Control and Prevention. But it’s also because there’s a really big question as to how many adults become infected with the strains of pneumococcus bacteria that the Prevnar vaccine targets.

Pneuomoccocus, it turns out, likes to live in the noses and throats of children. And kids have gotten three courses of the earlier Prevnar 7 since 1998, with the newer Prevnar 13 approved in 2010. As I’ve written previously, the introduction of Prevnar resulted in a dramatic reduction in the number of cases of pneumococcus infection in kids, making the disease virtually go away. A few resistant strains stuck around; developing the 13-strain version gave Pfizer a chance to take on those strains, too, and also to raise the price of the shot, which now costs $120 per course.

But when you get rid of pneumococcus in kids, you wind up with less of it in adults. As you can see in the below graphic from The Journal of Infectious Diseases,  giving Prevnar 7 to kids led the strains in the vaccine to go from causing a majority of infections in adults to causing a minority. There’s already been a dramatic drop in adult infections, the argument goes, and we’re getting it for free by giving Prevnar to kids. Is it worth the cost to recommend a new vaccine in adults?

Emilio Emini, the Pfizer senior vice president who pushed this vaccine through development, says that it is. For one thing, kids in the Netherlands get Prevnar; there was still enough benefit for the study to be positive. (There were 90 cases of vaccine-preventable pneumonia in the placebo group, versus 49 in the Prevnar group.) He says that in both this study and other studies that have been conducted in the United States, about 10% of adult patients presenting to the hospital with pneumonia are infected with these strains. That’s about 30,000 cases a year that could be prevented by giving Prevnar 13 to adults. And these can be costly infections, requiring long hospitalizations.

There is another, older vaccine from Merck. Unlike the Pfizer vaccine, which links up sugars from the outside of the bacterium’s coating to chemicals that make the immune system recognize them, Merck’s Pneumovax 23 contains only the sugars, and there’s lots of reason to think that it may not be as effective at provoking an immune response. There’s no definitive proof, like Pfizer’s big study, that Pneumovax prevents pneumonia cases. Pneumovax's efficacy was proven in a population of South African gold miners at high risk for infection; it's thought it may not be effective in older adults, where Prevnar now has been proven effective.  A U.S. study of Pneumovax in older adults did not show it prevented pneumonia. But Pneumovax does cover strains of pneumococcus that are not in Prevnar 13, and it is cheaper: just $68 per shot. So maybe it makes sense to keep using Pneumovax, the current recommended vaccine, instead? Then again, there may be issues with giving repeated doses with the older vaccine repeatedly as a booster if patients are at high risk  -- it may lose efficacy -- and there are some studies that indicate if you're going to give both vaccines, it's best to give Prevnar first.

“There’s no clear answer,” says Kenneth Bromberg, director of the Vaccine Research Center at The Brooklyn Hospital Center. “People have their opinion about this.”

Most observers expect ACIP to split the difference later this year, and to add Prevnar 13 as another option for patients. But there’s the possibility the committee could do more. In an all-out win case, Pfizer might convince it that patients should use Prevnar first, because there’s some evidence that Pneumovax delivers diminishing returns after booster shots but Prevnar does not. What’s at stake? Well, tens of thousands of case of pneumonia, and a sales boost for Pfizer that could be anywhere from $1 billion on the low end to several times that on the high one. We’ll know more later this year.