The pharmaceutical company Roche is cooperating with the World Health Organization and individual governments in planning for an avian flu pandemic.
The agreement represents a change of approach on the company’s part. It initially sought to exploit the full business potential of its drug oseltamivir (Tamiflu) with a strategy to go it alone.
But negative publicity, government pressure, the threat of compulsory licensing, and limited manufacturing capacity, should such a threat materialise, led the company to change its approach.
David Reddy, the leader of Roche’s global influenza task force, explained the steps that the company had taken to respond to the challenge, at the second Bird Flu Summit in Washington, DC, on 29 June.
Dr Reddy said that the company had introduced a tiered pricing arrangement for selling oseltamivir to help developing countries stockpile supplies.
A course of treatment with oseltamivir is about €26 (£18; $33) for seasonal influenza, as opposed to pandemic flu; about €15 for stockpiles in rich countries; and about €12 for stockpiles in poor countries.
With regard to compulsory licensing, he believes that Roche has been responsive in granting four regional licenses to produce oseltamivir.
When asked if Roche should further discount stockpile sales to developing countries, Dr Reddy said that the current price is about the same as available generics being produced under the licence agreements.
Growing regional stockpiles of oseltamivir are under the control of WHO, and 65 governments have ordered their own national stockpiles of the drug.
The efficacy of oseltamivir in treating generic influenza remains an open question to some. No controlled studies exist of it or any other antiviral drug in patients infected with H5N1 avian influenza. The virus has raised much concern that it will mutate to allow easy transmission between humans. But an international panel of experts assembled by WHO has declared it the drug of choice in treating H5N1 in treatment guidelines published in May 2006.
Dr Reddy described use of the drug when it was used in an outbreak of avian flu in Turkey earlier this year. Ten people were treated with oseltamivir: four died, and six recovered. “What we found was that for those who died, the mean time to receiving treatment was 8.5 days, versus 3.5 days for those who survived. This mirrors some of the animal data, where early intervention correlates with increased benefit.”
A consensus has emerged that, should an influenza pandemic occur, it is likely do so rapidly, leaving inadequate time to increase production of oseltamivir sufficiently to meet the need. The remedy is to stockpile the drug in preparation for that possibility.
Roche has dramatically increased capacity to make oseltamivir by expanding its own manufacturing capability, using subcontractors for intermediary steps of production, and granting regional licenses to produce generic versions of the drug in India, China (two companies), and South Africa.
The “global stockpile” consists of 1.5 million courses of treatment stored by Roche in Basel and 1.5 million courses of treatment purchased by the US government and stored in New Jersey. Dr Reddy called this a “fire blanket” that is available at the discretion of WHO to attempt to stop an outbreak at its source before it can spread.
Roche has agreed to ship requested doses of the drug to the airport closest to any outbreak within hours of an emergency being declared, and to turn supplies over to WHO.
Dr Reddy described their experience in shipping drugs to Turkey and Indonesia as “fire drills” that went well. But he cautioned, “These are very modest amounts, not three million courses of therapy. The logistical challenges should not be underestimated.” That is particularly true as outbreaks are likely to occur in isolated regions, with poor transportation infrastructure.
Oseltamivir has a certified shelf life of five years under normal conditions of temperature and humidity, and it may last significantly longer. Roche has offered to assay samples for potency at the five year mark for all stockpiled drugs.
WHO’s guidelines are available at www.who.int/csr/disease/avian_influenza/guidelines/pharmamanagement/en/index.html.