by Serena Tinari
www.manifesto.it Published: March 8, 2006
The case of the well-known Tamiflu: serves only one purpose, to bring in profits to Roche. A powerful communication strategy and a massive psychosis helped the Swiss multinational sell an astronomic quantity of a drug that had a bad start, was essentially worthless and hardly ever tested for the scope it was designed for.
Geneva, August 24, 2005. A press release of the World Health Organization announces that the pharmaceutical company Hoffmann-La Roche donated three million treatments of Tamiflu to the international community which will serve to fight avian flu in the poorest countries. “In case of a pandemic, and combined with other measures, the administration of Tamiflu could help limit illnesses and deaths and contain the explosion of the virus. Or to slow down its diffusion”, asserts the supreme public health authority. At the headquarters in Basel, the Roche high command must have celebrated an excellent return on the brand image. With the blessings of the WHO, the pharmaceutical giant is on the side of the poor. And through the announcement made by the WHO, in the age of avian flu, Tamiflu enters the media circus as the principle actor. It is a consecration. In the daily administration of numbers, being thrown at us with pandemic tone, between the stake of chickens burnt alive and “men in white” disinfecting, the “unique antiviral that could fight human avian flu” is propagating. Within a few months, and in spite it being conditional, sixty nations plan to ensure reserves for 25% of their population, while the pharmacies are taken by assault by those who mistrust the promises made by their governments. Roche announces that their factories are working day and night: since 2004 and till the end of 2006, the production of the precious white powder will be multiplied by ten.
A lesser drug
Strange destiny for a drug up to now considered by specialists as “mediocre”. Tamiflu – Oseltamivir is the active ingredient – is discovered in 1994 by researchers of Gilead Sciences, a bio pharmaceutical company headquartered in California. At Gilead, Secretary of Defense Donald Rumsfeld feels at home: he was the director in 1998, Chairman of the board of directors from 1997 to 2001 and is still shareholder. In 1996, Gilead traded the marketing rights of Tamiflu for 10% of sales. The drug arrived on the North American market and in Switzerland from 1999 to 2000, and in the majority of the European countries between 2002 and 2003. Indication: seasonal flu. Until the arrival of avian flu, Tamiflu was selling poorly – so poorly that rumors were circulating in the lounges of the pharmaceutical industry that Roche was thinking of withdrawing it. But this was no surprise for specialists. Tests conducted before commercialization indicated in fact that Oseltamivir, in jargon “neuraminidase inhibitor”, acts on strains “A” and “B” of influenza – strains that can only be detected with certainty after an appropriate exam. Absorbed within 48 hours after appearance of first symptoms, Tamiflu may reduce the duration of the flu by a day and a half. Modest advantage compared to taking milk with honey, aspirin and making a poultice. The Tamiflu miracle pill as a matter of fact is a flop. And Roche, in fact, wasn’t really interested in it any longer. As a consequence, in 2005 Gilead, at the termination of the contract, requested and obtained the revision of the 1996 agreement, stating that the Swiss multinational has not done enough to promote the drug and neglected to pay nearly 20 million dollars to it’s American partner. Gilead summarizes: “Roche received the marketing authorizations in 64 countries but only promoted it in 21 (…) and didn’t make it known to the doctors, patients and health authorities”. Roche denies this but paid: as of November the dispute is declared closed with reciprocal satisfaction.
What about efficacy?
But why would Roche not have invested it’s powerful communication and marketing resources on this drug? An answer appears spontaneously at the reading of articles and research published in specialized reviews. To the crucial question whether the drug is effective, there might not be sufficient scientific evidence. The criticism in the Swiss newsletter “Infomed/Pharmakritik” is harsh: “Based on current knowledge, no well defined group of sick patients exist, to whom we could advise to take a treatment based on Oseltamivir”. The French independent medical review “Prescrire” is categorical: “Besides collateral effects, we do not understand what it adds to the traditional symptomatic therapies”. In February 2006, “The Lancet” rams the point home. Researchers of the Cochrane Collaboration examined 50 studies on the efficacy of Tamiflu and came to the conclusion: “It is too modest to advise its use”. But if it’s effect on influenza is weak, no specialist can guarantee the efficacy of Tamiflu on human avian flu. First of all because it is a virus that does not exist. The actual strain hasn’t been transmitted between human beings, just a handful suspected cases have been reported in Asia. But if the virus would have gone through mutation, in the presence of 180 million dead birds, the human victims would be far more numerous than the few hundreds reported up to now. And especially, reports the spokesperson for avian flu from the WHO in Geneva, Dick Thompson, it is impossible to confirm that Tamiflu works, because “we have no clinical data to affirm this”. The hopes of governments worldwide have been triggered by the heavy artillery of the Roche strategy, in order to associate Oseltamivir to the arsenal of the feared pandemic. It is based on a lab test, whose conclusions have been communicated in 2004. Twenty rats have been infected by the virus H5N1; ten rats treated with another anti-viral died; the other ten received Oseltamivir and two survived. An experience repeated after that showed the same results: therefore on rats infected with avian flu, the treatment with Oseltamivir could have at least some results. But what about human beings? In the literature a few cases have been reported of people having been infected by avian flu and having been treated with Tamiflu. A Vietnamese study analyzed ten patients: of five treated with Tamiflu four died. A Dutch study dating back to 2003 is often quoted, but it was about another virus, (H7N7) and the results were defined as “non concluding”. “The Lancet” gave the deathblow in January: “We found no proof of efficacy of neuraminidase inhibitors on human avian flu”, wrote Tom Jefferson from the Cochrane Collaboration. Proofs of efficacy of Tamiflu are so weak, to the point of embarrassing the WHO spokesperson, who declares: “It is frustrating but it is the situation in which we are. The virus touched so few people around the world that we have no patients on which we could test Tamiflu”. Dick Thompson admits however that on this question there is neither any particular coordination program with Asian hospitals nor clinical tests underway. Besides: “We do not know what can happen in the future. Because if the virus would mutate and may be transmitted to man, it might not be the H5N1, and then we could hope that other antivirals would be effective”. And what will we do with the tons of Oseltamivir stored throughout the world? The answer given by insiders is unequivocal: in doubt, by measure of precaution and hoping that it might serve, we store reserves.
A safe drug?
The second basic question regarding drugs, beyond their efficacy, is the one of safety. According to Roche, Tamiflu has few side effects, of which nausea and vomiting. Thesis embraced by health organizations and a strong point of nebulous doubt: “we are not sure it will work”, say the experts, but at least…it won’t do any harm. But even here, there is no real consensus among the scientific community. Before its approval by health authorities, a drug is tested on a few thousand people and it is difficult to determine whether a rare side effect will appear. The degree of safety of a drug will be confirmed over the years, when millions of people will have used it. For Tamiflu, young and far from being a sales champion, the Pharmacovigilance network knows very little. Drugdex, an international database on the subject, regarding Oseltamivir, answers by a series of : “not tested”. In case of doubt, and in the expectation of punctual clinical studies, authorities and the pharmaceutical industry show their optimism, except in Japan: in this country where the precious pill has been sold the most, Tamiflu was correlated with the sudden death of several young children. The president of the Japanese Pharmacovigilance institute, Rokuro Hama, repeats this in medical congresses and scientific reviews since two years. In the British Medical Journal, Hama points out that children died of respiratory insufficiency and quotes three laboratory studies where “administration of Oseltamivir to baby rats provoqued death by respiratory insufficiency”. Therefore, based on these studies, it is not allowed to administer Tamiflu to children younger than a year old. Numerous researchers however, given the insufficient clinical data, have doubts regarding the age group between 1-12 years. From the point of view of health authorities, the argument regarding children is sore point for the opposite reason. In case of pandemic, they constitute the highest risk. And if Tamiflu is the only available remedy, it is necessary to give it to them too. For this reason the European and American authorities recently authorized its use for prophylactic reasons even on patients from 1 to 12 years. The other side effect of Tamiflu registered in Japan regards the mind: there have been behavioral changes and suicide among very young people who took it. According to Roche, this data is distorted because “in presence of high fever, the psychological condition of a patient may deteriorate”. By precaution, in May 2004, Japanese authorities added to the list of possible side effects of Tamiflu “neurological and psychological troubles: alteration of consciousness, abnormal behavior and hallucinations”. In November 2005, l’EMEA, the European authority that monitors drug security, after having received two warnings of suicide, asked Roche to provide all available clinical data regarding the effects on the psyche.
Meanwhile, profits galore
Among all this confusion, something is clear: Roche is making money hand over fist. In 2005, the turnover of Tamiflu surpassed the billion Euros and the multinational made 22,5 billion Euros, the best result in its history. Not bad for a drug whose efficacy is associated with a series of “ifs” and “maybe”. In the meantime, while half the world was imploring that production be increased, or that the patent for Tamiflu be released, in order to allow the production of “generics”, the Swiss pharmaceutical industry was feeding the legend. Coming from the plant Star Anise, grown in China, Tamiflu “has a production process through a 12 stage process that can require 6 to 8 months of work and sophisticated technology”. In October 2005 Roche announced that it was ready to negotiate. Pressure coming from the United Nations and the US has been heard, but it is the choice of the communication strategy that, once again, is phenomenal. Roche declares being preoccupied by public health and ready to discuss the conditions to release the transfer of license “to any government and company who will contact us”. Moreover, the World Trade Organization established in 2001 (and confirmed in 2003) that in case of health emergency, governments have the right to copy drugs regardless of patent protection. Anticipating such a step, Roche stands like Robin Hood – with a guarantee to receive part of the royalties. Given the success of its first donation, it marks up with another two million treatments – with the communiqué of the WHO stating: “We are thankful to Roche for its generous donation”. The production of the drug, that started at 5,5 million doses, is planned to reach 300 millions doses in 2007. Overseas, shareholders of Gilead are also doing quite well. Fortune writes (November 2005): “Thanks to the fear of a pandemic, the shares of Gilead have gone from 35 to 47 dollars in six months. The head of the Pentagon has earned a million dollars”. Serena Tinari