Apr 26, 2007 (CIDRAP News) – The Swiss pharmaceutical company Roche announced today it is scaling back production of oseltamivir (Tamiflu) because of waning demand, and simultaneously questioned whether countries stockpiling the drug are buying enough to protect their citizens in the event of an influenza pandemic.
The World Health Organization (WHO) recommends the antiviral drug as the first-line treatment for patients who have H5N1 avian influenza and has advised countries to stockpile it. In its most recent H5N1 treatment update, released last week, the WHO reaffirmed its Tamiflu recommendations.
In response to stockpile demands and the desire of some businesses to supply their employees with Tamiflu, Roche geared up its manufacturing capacity to more than 400 million doses per year. The company, at the request of the US Department of Health and Human Services (HHS), upgraded its US supply chain to utilize US sources for all phases of Tamiflu production and can now produce 80 million doses a year in the United States.
Plans to cut production
Despite the continuing pandemic threat, demand for Tamiflu seems to be dropping off, Roche executives said at a press briefing today. Eugene Tierney, global head of virology and transplantation for Roche, told reporters the company has so far this year received orders for only 215 million doses, most of which have already been produced.
"Today we can satisfy significant additional orders from governments and corporations, and unless demand picks up, Roche will be tailoring its production schedule accordingly," said William M. Burns, chief executive officer of Roche's pharma division, in a press release.
The company said it would maintain stocks of the ingredients it uses to make Tamiflu throughout its supply chain and would maintain close contact with its manufacturing partners so that it could respond quickly to surges in demand. Jan van Koeveringe, head of Roche's pharma global technical operations, told reporters it would take 4 months to restore production to its current output level.
Two events would prompt Roche to restore production to full capacity, van Koevering said: if inventories of key Tamiflu ingredients drop below target levels, or if the WHO raises the pandemic alert level from 3 to 4 (signaling increased human-to-human transmission).
Roche questions stockpiling goals
Tierney said that among the more than 80 countries stockpiling Tamiflu, coverage plans vary widely. For example, Greece and Brazil plan to buy enough to treat about 5% of their populations, whereas Switzerland, Kuwait, Luxemborg, Australia, and France aim to have enough to treat more than 40% of their populations. The US stockpile plan would cover 25% of the population.
"We've taken capacity constraints out of the equation now," said David Reddy, leader of Roche's pandemic taskforce, at today's press conference. "The question now is how much do governments want to be prepared for wave one of a pandemic?"
Government antiviral stockpiles that cover only 20% to 25% of a population may not be enough to mitigate the impact of an influenza pandemic, Reddy said.
Citing mathematical models that appeared in the medical literature in 2005 and 2006, Reddy said countries could decrease the clinical attack rate of a circulating pandemic virus by boosting their stockpiles to levels that would allow not just treatment of sick patients but also preventive use (postexposure prophylaxis) for their household and other contacts.
According to the modeling studies, Reddy said, stockpiling enough Tamiflu for 57% of a country's population would allow it to provide enough treatment and postexposure prophylaxis, including family contacts, to lower its clinical attack rate during a pandemic to 22%. Stockpiling enough for 102% of the population would enable a country to expand prophylaxis to other contacts and reduce the clinical attack rate to 13%, he said.
Reddy said Roche is concerned that many government Tamiflu stockpile programs lack important details such as priority lists of groups to receive the drug, detailed logistical plans for distribution, and clarifications on treatment versus prevention.
However, he lauded governments that are encouraging businesses to prepare their own pandemic plans. He said corporate Tamifu programs for employees can help ensure that critical goods and services are delivered during a pandemic. Roche said it has received Tamiflu orders from more than 250 corporations, accounting for about 5 million doses.
In other comments, the company said several studies are under way to clarify how to make optimal use of Tamiflu. For example researchers from Southeast Asia and the United States will soon test whether doubling the standard dosage of Tamiflu will improve patients' chances of overcoming either the often-deadly H5N1 virus or severe seasonal flu.
Reddy said the same research group, known as the Southeast Asia Influenza Clinical Research Network, also has plans to study long-term prophylaxis for healthcare workers. A 6-week course has already been studied and approved, he said, but the researchers will explore whether 20 weeks of preventive treatment for healthcare workers is safe and effective.
Current and future research activities and collaborations, he said, also include:
- Preclinical virology studies to characterize how different H5N1 strains respond to Tamiflu
- An avian flu registry to collect clinical data on the virus and use of Tamiflu
- Postexposure prophylaxis case studies
- A study of the feasibility of an intravenous formulation
- Monitoring of H5N1 virus resistance to Tamiflu
- Safety profile studies for Tamiflu use in children younger than 1 year.
Apr 26 Roche press release
Apr 19 WHO summary of H5N1 treatment recommendations
Mar 29 CIDRAP News article "International network to study high-dose Tamiflu"