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Insight & Intelligence : Jan 21, 2013
Not Quite 1918, but Flu Still Deadly
Authorities and manufacturers look ahead to new vaccines and immunization efforts while scrambling to deal with spot shortages.!--h2>
The first flu was described by Hippocrates in 412 B.C. The deadliest flu was the 1918 pandemic, in which 20 million people died among the 500 million infected.
This year’s flu outbreak is unlikely to make as much history as those two cases, but remains serious enough to worry vaccine makers and public health officials. As of Jan. 12, according to CDC data released Friday, 29 children have died and 5,249 Americans have been hospitalized for flu-associated conditions. Flu and pneumonia accounted for 8.3% of all reported deaths the second week of January, compared with the normal 7.3%. The virus appeared to be worsening in the U.S.: Thirty states showed high levels of influenza-like illness, up from 24 the previous week. California became the 48th state to report “widespread” flu activity.
Most worrisome are the spot shortages of flu vaccine that have spread with the virus, despite pharma manufacturers producing 145 million doses this season. More than 129 million had been distributed as of Jan. 11. FDA approved two vaccines from GlaxoSmithKline, and one each from AstraZeneca’s MedImmune subsidiary, Australia-based CSL, Roche’s Genentech unit, Novartis, and Sanofi’s vaccine unit Sanofi Pasteur.
Sanofi Pasteur leads in flu vaccine production, making more than 60 million doses of Fluzone for the U.S. market, “and are shipping some additional doses now to healthcare providers,” spokeswoman Donna Cary said. A total global figure is unavailable, though last year Sanofi Pasteur completed a record production of more than 200 million doses—about 40 % of the influenza vaccines distributed worldwide.
Sanofi Pasteur blamed lower U.S. Fluzone supplies compared to a year ago for “a tough comparison” in Q3 2012 sales of its seasonal flu vaccine. They dipped 8% at constant exchange rates, to €608 million ($810 million), even though that number is about 1% above the €602 million ($802 million) of third quarter 2011.
“The ability to really reap rewards from a difficult flu season is limited by their ability to manufacture the vaccine,” Damien Conover, CFA, a director covering the healthcare industry for Morningstar, told GEN.
When results for all of 2012–2013 emerge, Conover added, “Sanofi could potentially see sales there actually move the needle. As you move down the list [of vaccine manufacturers], it’s harder to see as much of a bump to overall sales, just because they don’t contribute as much.”
Morningstar has estimates for only one flu product: Genentech’s Tamiflu is projected to more-than-double to about $750 million this year from about $350 million in the 2011–2012 flu season, with overall 2013 Roche revenue expected to rise about 1%, to $44.8 billion. Tamiflu sales were disappointing in the first half of 2012, falling 18% at constant exchange rates to CHF 221 million ($236.5 million) from CHF 262 million ($280.4 million) in the first six months of 2011.
Tamiflu is sold in capsules (75 mg, 45 mg, and 30 mg) and liquid. On Dec. 21, FDA approved expanded use of Tamiflu to treat infants two weeks old or older, with up to two days of flu symptoms. Since Tamiflu liquid for children is in short supply, Genentech has advised pharmacists to dissolve capsules in sweetened liquids.
Genentech recently worked with FDA to release a reserve stock of Tamiflu 75 mg capsules with different packaging than seen in the U.S. “With the addition of these reserve supplies, we anticipate having sufficient supply of Tamiflu capsules to meet demand for this flu season,” Genentech said Thursday in a statement.
Novartis distributed 36 million doses of Fluvirin this season, 6 million above its 30-million-dose commitment, spokeswoman Elizabeth Powers told GEN. “We have completed shipments of Fluvirin to the U.S. market and are currently working with public sector stakeholders and our distributors to help ensure that our flu vaccines are broadly available and to address urgent public health needs. Additionally, we are evaluating options to meet increased demand, if needed.”
Fulfilling Existing Orders
GlaxoSmithKline distributed all 25 million doses of Fluarix and FluLaval, the latter made by GSK's ID Biomedical subsidiary. “We are not in a position to take new orders for Fluarix or FluLaval for this year’s flu season,” GSK spokesman Rob Perry told GEN. “We are fulfilling existing orders from our U.S. distribution facility in Marietta, PA. We have orders in place for all remaining supply. We do anticipate fulfilling all existing orders by early February.”
Tor Constantino, director of product public relations for MedImmune, told GEN his company produced all 12 million doses of Flumist committed for 2012–13. In less than a week, the company sold all 70,000 doses with a March expiration date and 10,000 with February expirations, leaving it on Jan. 15 with just 300,000 doses to sell, all set to expire in February.
“We’ve met all of our customer orders for the current season,” Constantino said. “While we’re not seeing additional re-orders for this season, we are taking orders for next season.”
CSL’s Afluria is distributed in the U.S. by Merck & Co., which shipped the last of its approximately 11 million doses last week, Merck spokeswoman Deb Wambold told GEN on Friday.
“We have put all of our doses out into the marketplace, either directly to customers who were looking for additional doses based on demand, as well as a lot to the larger distributors,” Wambold said.
The shortages followed a rush to doctors’ offices and drug stores once patients realized this year’s flu season would be more intense than the mild outbreaks of the two previous years. Blame it on the flu virus’ stubborn ability to mutate into new strains, forcing public health agencies to play catch-up every few years.
There’s Vaccine Out There
“We’re seeing a season unfold where H3N2 is the strain that is circulating the most, and in years past, when that strain has circulated, we tend to see more moderate to severe flu, as far as level of activity—more hospitalizations, more deaths. It tends to impact young children and the elderly more,” CDC spokesman Tom Skinner told GEN. “When that happens, sometimes demand for vaccine goes up.”
“The bottom line is there’s vaccine out there. There should be enough vaccine out there to meet demand, but people who want to get vaccinated may have to look around several places for it,” Skinner acknowledged.
Skinner said CDC is tracking vaccine supply, surveying where shortages are occurring, speaking with retailers so they can reorder vaccine if needed, and sharing information with professional groups like doctors and pharmacies. CDC, he added, continues to urge vaccination of all people six months old and up: “We’ve got to continue to push these messages, so that more and more people each year step forward to get vaccinated. Only then will the manufacturers make more and more vaccine to meet the demand.”
After the 2009 H1N1 flu pandemic, CDC expanded its flu vaccine recommendations beyond seniors and people with some chronic diseases. “It encouraged some in private industry to say, ‘Well, the U.S. market is going to expand a little bit.’ But it really in a significant way did not happen,” Adel Mahmoud, M.D., Ph.D., professor of molecular biology and public policy at Princeton University, told GEN. “When you look at the uptake of the vaccine in our country, year in and year out, it’s about 60% in targeted age groups that have historically been the focus of the effort, and 30–40% in the other groups if not less. You have a lot of room to expand the vaccination effort.”
Government is unlikely to do so, Dr. Mahmoud added, by stoking more vaccine production, either by fiat or by buying the doses, given the economic risk to manufacturers and political risk of promoting vaccine waste.
More Flu Options
It’s too soon to predict how this year’s outbreak will affect plans for next flu season. It’s not too soon, however, to know FDA will have new flu vaccines to consider. The agency approved 10 new flu vaccines in 2012, and one already this year. Two can be produced rapidly during outbreaks since they involve alternatives to the decades-old methods of growing, then inactivating a flu virus in the eggs of chickens.
Protein Sciences won FDA approval Jan. 16 for Flublok, consisting of three full-length, recombinant flu hemagglutinin (rHA) proteins designed to fight influenza virus A strains, H1N1 and H3N2, and an influenza virus B strain in adults ages 18 to 49. Two months earlier, FDA approved Novartis’ Flucelvax®, the first cell-culture-derived vaccine using mammalian cells. Both vaccines were developed with funding from the U.S. Biomedical Advanced Research and Development Authority (BARDA).
“The company expects full launch for Flucelvax in the 2013–14 flu season,” Powers of Novartis said. Full-scale production won’t occur until the company’s new Holly Springs, NC, plant becomes fully operational. Novartis plans to file for site licensure this year, but cautions it cannot predict timing of government approvals.
Also new are the four-flu-strain vaccines two manufacturers plan to roll out next season. GlaxoSmithKline’s Fluarix® Quadrivalent last month became the first intramuscular vaccine designed to fight two A and two B strains in adults and children three years and older.
AstraZeneca’s MedImmune subsidiary will market the first FDA-approved quadrivalent vaccine, the nasal spray FluMist Quadrivalent for patients ages 2 to 49. “It will completely replace the trivalent formulation here in the U.S. The trivalent formulation will be available in several ex-U.S. markets” including Canada and the Europe-Middle East-Africa region, where it will be sold as Fluenz®, Constantino said.
FDA approving even one or two of the new vaccines for 2013–14 should reduce the prospects of spot shortages, absent a particularly virulent flu strain. And since authorities can only predict what strains will cause flu next season, health authorities will need to continue promoting new vaccine R&D as strongly as preventive vaccination for the foreseeable future.
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