Roche has announced plans to increase production of its flu drug Tamiflu, as part of the response to a huge global surge in demand. With an annual production capacity of 300 million doses expected by 2007, Datamonitor’s Infectious Disease analyst Mark Belsey asks whether Roche’s latest move will be enough to prevent a flu pandemic from claiming millions of lives...

The latest round in the fight to ensure that there will be sufficient antiviral drugs to treat a potential flu pandemic stepped up a gear as Roche announced that it was boosting production of its antiviral Tamiflu (oseltamivir).

A mutation of the avian influenza virus H5N1 to a form that can be passed between humans is believed to be likely to trigger the next pandemic, and Tamiflu is thought to be one of the few drugs effective against viruses such as H5N1. Tamiflu is playing an increasingly prominent role in the influenza preparedness plans for European countries and the US, with many countries stockpiling the drug to combat future pandemics.

Earlier in November 2005, US president George W Bush pushed US Congress to approve a $7.1 billion pandemic-busting flu fund, of which $1 billion was earmarked for acquisition of antivirals. The WHO is pushing countries to stockpile antivirals such as Tamiflu, and both the UK and the US are recommending Tamiflu for the treatment and prevention of flu.

The sales of antivirals such as Tamiflu and GlaxoSmithKline’s Relenza (zanamivir) are being driven not only by pandemic fears, but also by a shift towards using antivirals for flu prevention and treatment, following Chiron’s recent flu vaccine manufacturing problems. Together, these factors have resulted in a high global demand of the product.

Manufacturing shortfall

The manufacturing process for Tamiflu involves a complex and lengthy series of stages that turn the starting ingredient, shikimic acid, into Tamiflu. This level of complication has contributed to concerns over manufacturing capacity, which have recently resulted in Roche halting supply of the drug to major markets such as the US and Hong Kong in October-November 2005. These restrictions were put in place to prevent hoarding, to help guarantee a supply to treat both the conventional flu cases in Winter 2005, and to ensure that there are sufficient supplies to treat a pandemic.

Roche recently admitted that it cannot meet the international demand for the drug by itself, even though it is ramping up production to 10-times the amount of 2003 production, over the short term. Fears over a manufacturing shortfall has led Roche to draw up a shortlist from 150 drug manufacturers who have offered to produce Tamiflu under license. Earlier in November 2005, the Korean Food and Drug Administation announced that Roche has given permission for local South Korean manufacturers to produce the drug. These moves hint that Roche realizes that to assert patent protection rights and maximize revenue from the drug, it must explore every avenue of manufacturing and licensing.

Generic impact

If Roche fails to supply enough Tamiflu, governments may turn to generic drug manufacturers for drug supplies. Indeed, in countries such as Thailand, where Tamiflu is not believed to have patent protection, plans for the manufacture of generic copies of the drug are being drawn up. To capitalize on the market potential for generic Tamiflu, the Indian generic drugs companies Cipla and Ranbaxy have announced that they have developed a manufacturing process for oseltamivir, which is being aimed at countries where Tamiflu lacks strong patent protection. However, difficulties associated with sourcing shikimic acid may retard generic incursion of the Tamiflu market, unless generic firms gain access to a source that is not dependent on star anise.

Problems with drug supply may increase the amount of counterfeit Tamiflu. Counterfeit medicines are already a concern in the Far East: the region where an avian flu outbreak is most likely to originate. Indeed, the Chinese government has recently warned of counterfeit flu vaccines in regions of China at risk from avian flu. If counterfeit Tamiflu contains no oseltamivir, then they are unlikely to prevent the spread of influenza. Meanwhile, if they contain a suboptimal dose, they are likely to increase viral resistance to the drug.

Despite the recent announcement to upscale Tamiflu production, Datamonitor believes that Roche has a fight on to ensure that it maximizes the revenue potential of this drug. Given the extent of demand for the product, generic competition, which is already high, is set to accelerate. Ironically, even if Roche succeeds in meeting supply demands, the drug may become increasingly ineffective due to resistance. Indeed, a recent study in Japan indicated that neuraminase mutations resulting in Tamiflu resistance were found in 18% of patients. To reduce the reliance on Tamiflu, flu treatment and prevention strategies should look to increase the sourcing of GSK’s Relenza, together with novel antivirals.

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