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Tiny Taiwan Preps for Worst; H7N9 Vaccine Plan in Place

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By Dave Silver
Contributing Writer

TAIPEI, Taiwan – With H7N9, Taiwan is facing another pandemic influenza threat from China. It's déjà vu all over again. Sixty-one people in China were infected with a new strain of avian flu that until now had been considered unable to be passed on to humans.

As of Monday, 14 people have died, according to the Chinese government. Tiny Taiwan is watching its big neighbor closely, still smarting from memories of the 2003 SARS crisis when China was accused of concealing the number of infections and deaths. That steeled the Taiwan government to be more self-sufficient and better prepared.

The new attitude paid off. The country has since faced down the 2005 H5N1 avian flu scare followed by the 2009 H1N1 swine flu pandemic.

On this occasion, Taiwan is wasting no time putting the pieces in place for a coordinated multi-pronged response should the situation in China deteriorate rapidly or if the virus reach Taiwan's shores. The Center for Disease Control (CDC), a unit of Taiwan's Department of Health (DOH), has a command center in Taipei already in place with daily briefings to keep the media and Taiwan's jittery public up-to-date.

Taiwan's CDC has stockpiled enough antivirals to safeguard at least 10 percent of the island's population, in accordance with World Health Organization (WHO) recommendations. Also coming together is a plan to produce H7N9 vaccines, should it be necessary.

While to date only bird-to-human infections have been documented, fears that the virus will mutate into a human-to-human infection form are very real. Currently the growth in reported infections is still slow. Not such a good sign is that the locations of reported infection sites are relatively spread out, not concentrated in one area as would be expected for a viral mutation of this nature. Epidemiologists are a little uneasy.

Recent studies on exactly how big a hit the world economy would take from the combined supply and demand shock of a pandemic are hard to come by. But fresh from the obvious economic effects of the SARS outbreak in 2003, the Asian Development Bank released a report in 2005 looking at the effect a global H5N1 pandemic would have on Asian economies and predicted significant damage: at least a 4.6 percent drop in GDP for China, 6.9 percent reduction for Taiwan and a 19.9 percent hit for Singapore from a pandemic event.

Vaccine Makers Gear Up

If Taiwan's CDC determines the H7N9 outbreak has breached certain thresholds, such as human-to-human infection or infections reported in Taiwan, then it will vaccinate certain segments of the population to contain its further spread.

Adimmune Corp., of Taipei, (TPE:4142) is the island's only private manufacturer of vaccines for human use, and the only one with experience in making vaccines in high volumes within a short period of time. As such it is well placed to benefit from a decision from the CDC to begin manufacturing H7N9 vaccines.

Adimmune's rise has been rapid. Following the H5N1 scare of 2005, the government declared self-sufficiency in vaccines a national priority. Adimmune was unexpectedly declared the winner of the government's heralded "build, own, operate" (BOO) project to construct a production facility for seasonal and pandemic influenza vaccines. That is, only after after-the-bell negotiations with initial bid winner GlaxoSmithKline plc, of London, were unsuccessful, and the next winner in line Akzo Nobel NV, of Amsterdam, the Netherlands, dropped out when it suddenly merged with another company.

After winning the bid, Adimmune partnered with Dutch vaccine firm Crucell Holland BV, of Leiden, the Netherlands, a Johnson & Johnson pharmaceutical company, to construct its plant and be its technology partner for future projects. During the 2009 swine flu pandemic, Adimmune and Novartis AG, of Basel, Switzerland, were jointly awarded the rights by to produce H1N1 vaccine, with a directive to produce 10 million and 5 million doses respectively for Taiwan's local population.

The Adimmune vaccine was offered to the government for only NT$199 (US$6.64), compared to Novartis's price of NT$400 (US$13.36). By the end of the year, Adimmune had produced and distributed more than 7 million doses out of its 10 million dose contract, while Novartis produced 2 million doses. There were eyebrows raised at the speed at which Adimmune received approval for its new vaccine, being the first time it had produced a human vaccine on its own from scratch instead of repackaging other companies' products.

Simon Kao, Adimmune vice president and company spokesman, told BioWorld Today that requests for the H7N9 virus strands necessary to construct a working vaccine had been sent to the US Centers for Disease Control and Prevention and the WHO, and that these groups had agreed to provide them to the Taiwan National Health Research Institutes (NHRI). Once the viral material is received, vaccine production would be relatively swift.

"We'll need only six to eight weeks' time to come up with a vaccine, and we aim to produce between 5 million and 10 million doses," Kao said. "We're using the H1N1 vaccine for which we already have license to make a mockup vaccine, to get quick approval from the government."

Another potential vaccine player is Medigen Biotechnology Corp., of Taipei, (TPE:3176). A relative newcomer to vaccine production, its P1-88 drug candidate for postsurgery stage liver cancer is currently in a multi-country multi-site Phase III trial. The company has other interests, including a strong diagnostics arm, a therapeutic monoclonal antibodies drug discovery and development division, and a new vaccine development business.

Medigen has developed a cell-based vaccine production system, TideCell, where cell-supporting medium flows over the vaccine-producing cells in a tide-like fashion, reportedly allowing higher cell densities and higher yields than conventional production methods.

The company has plans to build a plant to demonstrate its technology, but it's still at the drawing board stage.

Medigen CEO Stanley Chang told BioWorld Today how the company could still be considered in the running for this project without its own working manufacturing facility.

"Medigen has entered into a collaboration and outsourcing agreement with the NHRI, which has its own GMP-certified facility in place," Chang said. "Actually, we have been working with NHRI on cell-based bioreactor technology for vaccine production since 2009."

Last week, after the government said it would meet with and discuss details with prospective participants in a H7N9 vaccine production project, Adimmune and Medigen stocks shot up to their daily limit (7 percent under Taiwan stock law), although both stock prices have fallen since on profit taking.

Stockpiling Antivirals

In a pandemic influenza outbreak, neuraminidase inhibitor drugs such as Roche AG's Tamiflu (oseltamivir) and GlaxoSmithKline's Relenza (zanamivir) are administered in two ways. First to those with who have become infected; second to those who have been in close contact with those infected. The WHO has recommended that countries stockpile enough pandemic influenza antiviral meds to cover at least 10 percent of their populations.

In the buildup to the 2005 H5N1 avian flu scare, Taiwan was concerned that Roche, maker of the antiviral Tamiflu, could not provide the drug quickly enough nor in quantities enough to protect its citizens in case the situation deteriorated rapidly, nor allow Taiwan to manufacture the drug itself under a Roche-approved license agreement.

Taiwan's DOH thus threatened that it would have no choice but to make its own version without permission from Roche, citing World Trade Organization 'compulsory licensing' provisions allowed during public health emergencies. Roche dug in its heels, claiming that no company had the skill to make a copy of Tamiflu, but Taiwan's NHRI then demonstrated it could make a version of the drug using a process of its own design, and a highly public standoff ensued.

After the dust cleared Roche did enough to convince Taiwan it could in fact deliver enough product after all, and threats to make unauthorized versions of the drug in Taiwan were rescinded.

"Current stocks of Tamiflu stand at 20 million doses, enough for 2 million courses of two doses a day for five days. In addition to Tamiflu, there are 1.5 million courses of Relenza in stock," said Angela Huang, Taiwan's CDC spokeswoman. She confirmed that Taiwan's Tamiflu stocks are all the genuine article, purchased from Roche.

The only other antiviral drug under consideration is Rapiacta (peramivir), developed by BioCryst Pharmaceuticals Inc., of Research Triangle Park, N.C. Rapiacta is licensed to Shionogi & Co., Ltd., of Osaka, Japan, for Taiwan and Japan markets, and to Green Cross Corp., of Seoul, South Korea, (KS:006280) for the Korean market. The drug is still considered experimental and as yet not officially approved for use in most countries including Taiwan, although the CDC has been stockpiling the drug since 2009 for use in severe cases of influenza. As an intravenous drug, it can treat patients in a coma who may otherwise be unable to take other antivirals – particularly Relenza, which is administered via inhaler.