An investigation by the Bureau of Investigative Journalism (BIJ) for The Independent has raised questions about the only independent study to find evidence that the drug, Cipralex, is clinically more effective than its out-of-patent predecessor, Cipramil. Both have a similar main ingredient but Cipralex costs £14.91, while the older Cipramil is available for just £1.31.
The inquiry sheds light on the lengths to which pharmaceutical companies go to extend the lives of drugs whose patents are about to run out.
Cipralex, or Lexapro, as it is known in the US, is one of the most widely prescribed antidepressants in the world, but has been criticised for being little different from Cipramil, whose patent expired in 2002.
There has only ever been one independent, direct comparative study which suggests that Cipralex is clinically more effective. The Bureau’s investigation has now established connections between an individual working for Lundbeck, the Danish company that makes both Cipralex and Cipramil, and Arbacom, a Russian company that sponsored the independent head to head trial.
That trial helped to make the case for the new drug to clinicians, costing the NHS millions of pounds more in prescription costs. Last year, the health service spent about £3.3m more on Cipralex than on Cipramil, although the older drug was prescribed nine times as often. A paper based on the Arbacom trial, which was published in November 2007 in the medical journal Clinical Therapeutics, acknowledged "Alexander N Postnov and Markus Kornfeld at Arbacom for their help in revising the manuscript". It appears that Mr Kornfeld may have assisted at the same time that he and his wife, Asa, were working for Lundbeck.
The BIJ has seen an email from Mr Kornfeld, dated August 2005, in which he sent a protocol for the trial to a Russian woman, copied to someone called "Alex", with a message listing errors in the protocol. In August 2005, Mr Kornfeld was a Lundbeck consultant and his wife was a senior employee.
Mr Kornfeld's email also forwarded a case-report form. The document's properties appear to show this was created only two days previously, and had been modified by a different Lundbeck employee. Mr and Mrs Kornfeld no longer work at Lundbeck and neither responded to requests for comment. Anders Gersel Pedersen, Lundbeck's executive vice-president for drug development, agreed that Mr Kornfeld was a consultant at the time but said nobody at Lundbeck, to the best of the company's knowledge, had known about the Russian Arbacom trial.
The BIJ was unable to contact anyone from Arbacom, which does not appear to have been named as a sponsor of any published research before or since. The bureau uncovered further connections between Lundbeck and Arbacom. While the Arbacom trial was under way, Lundbeck entered into a research contract for an epilepsy drug with another Russian company.
In 2006 and 2007, when the Cipralex trial was being carried out, Lundbeck negotiated a research contract for an epilepsy treatment, VLB01, with the Russian firm Valexpharm. Documents seen by the bureau attach a value of $2m to the deal. Mr Kornfeld and Alexander Postnov, who were acknowledged in the Clinical Therapeutics paper about the Cipralex trial, were sent the contract. It is not clear who Mr Kornfeld was working for at this time, but Mr Postnov was using his Arbacom email address. Valexpharm appears in some listings at the same address as Arbacom, and Valexpharm appears to have registered Arbacom's telephone numbers. Another employee apart from Mr Postnov appears to have worked for both firms.
A spokeswoman for Sistema, Valexpharm's parent company at the time of the trial, denied that Arbacom was related to Sistema in any way.
However, Valexpharm's current chief executive Alexander Bakhutashvili, a former president of Valexpharm's immediate parent company Binnopharm, described Arbacom as a "partner generic company".
Mr Pedersen insisted that there was "absolutely no linkage" between the epilepsy drug contract and Arbacom's Cipralex trial. He said Arbacom had been trying to prove that Cipralex and Cipramil were identical, with the aim of producing a cheaper version of the former. When the results came out proving the clear superiority of Cipralex, he said, Arbacom offered to sell the data to Lundbeck. "We told them to publish," Mr Pedersen said. The company ended up paying for Arbacom's data, he added, but this was its only involvement in the trial. "Regulators prefer studies done by pharmaceutical companies because they are rigorous," Mr Pedersen said. "There was no reason at all for us to be involved with the Arbacom trial."
But questions remain over whether Cipralex represents good value for money to the NHS. The drug has been cited as an example of "evergreening" – a strategy manufacturers use to extend the life of a drug patent. When a drug is about to go off-patent, which would allow it to be copied and sold in a cheaper generic form, the company slightly alters the chemical make-up of its drug and files a new patent. This version is then protected and sold as a new drug, although it often contains similar ingredients to the old one.
Cipramil's patent expired in 2002, at a time when it accounted for 80 per cent of Lundbeck's revenues. Just before this, Lundbeck released Cipralex on to the market. In an article in the British Medical Journal, a senior cardiologist argued: "When resources are limited, giving one patient an expensive drug with no added value when cheaper alternatives exist stops other patients getting treatments they need."
Lundbeck rejected suggestions of "evergreening" in the case of Cipramil and Cipralex. "That is simply not the case," said Mr Pedersen.
A spokeswoman from the Department of Health said: “We are modernising the NHS so we can give patients better access to the medicines they need. That is why we are changing the way drugs are priced to ensure they offer value for money.
“Doctors should be able to focus on what matters most - achieving the best health outcomes for their patient. Value-based pricing will ensure that the price the NHS pays for medicines is based on an assessment of their value, looking at the benefits for the patient, unmet need, therapeutic innovation and benefit to society as a whole.”
www.thebureauinvestigates.com
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