Tag Archives: Novartis

Quickening Pandemic Flu Vaccine Production

If a strain of avian H5N1 influenza that readily spread from person to person were to appear in the real world, the great fear is that it would produce a deadly pandemic to dwarf what happened in 1918.

The best defense against flu pandemics are vaccines, and the most recent experience with a global flu pandemic, in 2009, highlighted the gaps that existed in getting vaccine quickly made in large amounts. Three years ago, despite the U.S. government marshaling all its infectious disease-fighting muscle, the effort wound up delivering most of the vaccine too late to matter. The pandemic peaked in October 2009, while the vaccine supply didn’t hit its stride until sometime in December.

Novartis influenza-vaccine plant in Holly Springs, N.C./courtesy Novartis

In a report published today in Science as part of its H5N1 flu package, Dr. Rino Rappuoli, head of vaccines research for Novartis, spelled out seven steps that could hasten vaccine production for a newly appearing pandemic flu. The two most novel moves involve having vaccine manufacturers prepare in advance synthetic “vaccine seed” viruses and also adopting new ways to quantify viral antigens, a process that alone took about 2 months in 2009, he said. Adopting these two technological innovations could transform the vaccine-producing process “from a mid-20th century system … into a 21st century system of instantaneous electronic information exchange followed by immediate production.”

The modernized system would mean sequencing a newly isolated pandemic virus in the field and then — instead of shipping the virus — just sending gene sequences, followed by replicating the hemagglutinin gene at a remote site, putting the new gene into a waiting scaffold vaccine virus, and launching vaccine production.

If these two changes had been in place in 2009, “the vaccine would have been available in large quantities before the peak of viral infection,” Dr. Rappuoli said in his paper.

More importantly, speaking at a June 20 press conference Dr. Anthony Fauci said that the National Institutes of Health, as well as the Centers for Disease Control and Prevention and the Food and Drug Administration, had already begun to move on this, adopting “the fundamental principles of bringing influenza vaccinology into the 21st century.” Steps already taken along the lines of what Dr. Rappuoli suggested carry the potential for “a significant change right now” in the time needed to get out a pandemic vaccine, Dr. Fauci said.

He particularly cited NIH studies underway using an immunoadjuvant to expand the coverage potential of stockpiled H5N1 vaccine, a step that would “markedly accelerate availability.

“We are right now in a much better position [to distribute pandemic vaccine quickly] than we were in 2009 when we had vaccine available only after the peak of the H1N1 pandemic,” Dr. Fauci said.

—Mitchel Zoler (on Twitter @mitchelzoler)

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Filed under Health Policy, IMNG, Infectious Diseases, Internal Medicine, Primary care

HPV Changes the Face of Head/Neck Cancer

Just a few years ago, tobacco and alcohol use were presumed to be the main causes of head and neck cancers. Evidence of oropharyngeal cancer associated with human papillomavirus (HPV) first appeared about 10 years ago, but it wasn’t until 2010, with the publication of 2 papers showing far greater survival among HPV-positive patients with head and neck cancer, that oncologists suddenly realized that they were likely dealing with two distinct diseases.

“It’s become clear that the disease we thought was one disease related to tobacco and alcohol is now being parsed into two major categories,” Dr. Maura L. Gillison said last week in Phoenix at the 2012 Multidisciplinary Head and Neck Cancer Symposium. At the meeting, she presented her group’s data showing that the overall prevalence of oral HPV infection in people aged 14-69 years is 6.9%, and that the prevalence is much higher among men than women. The Merck-supported trial paper was published online in JAMA on January 26, coinciding with her presentation.

Tissue section from a head and neck cancer patient / Courtesy of Tom Carey, Ph.D.

In a separate talk, Dr. Gillison summarized previous work from her group showing that the incidence of HPV-related cancer is rising while HPV-negative cancer is declining, consistent with the decline in tobacco use and changes in sexual behavior that increase HPV transmission. Overall survival of head and neck cancer has improved over the last decade, a trend that is likely due both to the improved prognosis among HPV-positive patients and to the decline in tobacco use rather than to advances in treatment, she said.

This recently heightened role of HPV in head and neck cancer  – and the awareness of it – has impacted the field of oncology in several ways. For one, it has dramatically changed the way research is done, conference chair Dr. Ezra Cohen told me. “It has made a tremendous difference in the way clinical trials are conducted, because it makes absolutely no sense to lump these patients together. Now all clinical trials will either stratify for HPV status or design completely separate studies, because they truly are two biologically different diseases.”

Clinically, patients with head and neck cancers are now routinely tested for HPV. This wasn’t the case prior to 2010. And those who test positive are counseled differently, since their prognosis is better. Indeed, Dr. Cohen said, HPV-positive head/neck cancer patients appear to respond better to just about every type of treatment, including surgery.

What’s more, Dr. Gillison told me, HPV has essentially upended some of the tools oncologists use to predict outcomes in head and neck cancer patients. One example is the current tumor staging system, which doesn’t take into account HPV status. A Stage 3 or 4 cancer which carries a poor prognosis among HPV-negative patients might carry the prognosis now associated with Stage 1 cancer among those who are HPV-positive. And another factor that has been shown to predict poor outcome in HPV-negative patients, the presence of extracapsular extension, appears to have little impact in those who are HPV-positive.

“So all these things that we take as firmly established and drivers of treatment decisions in this new setting are all in question,” she said.

Tissue section from the same head/neck cancer, with brown stain of an HPV marker protein called p16 / Courtesy of Tom Carey, Ph.D.

Thus far there have been no major changes in treatment, but Dr. Cohen believes that is likely to change as more data become available. He is currently leading a clinical trial  in collaboration with Novartis Pharmaceuticals looking at treatment with reduced radiation doses – and thereby reduced toxicity – for patients who have a good response to induction chemotherapy. Such patients are usually HPV positive.

Another study, funded by the National Cancer Institute, randomizes HPV positive patients to radiation combined with either chemotherapy or a monoclonal antibody, with the hypothesis that the latter will be better tolerated.

Dr. Cohen cautioned that treatment changes won’t come immediately. “Many of us in the field believe that there will be different therapies developed for [HPV-positive] patients, but it takes time to do that. It’s hard to make those changes, especially when we are curing the majority of these patients.”

-Miriam E. Tucker (@MiriamETucker on Twitter)

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