The drug’s manufacturer was aware of the negative results of the Solidarity trial before the European Commission struck a procurement deal with it, finds an investigation.
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On 7 October the European Commission struck a so called joint procurement framework deal with the drug manufacturer Gilead, after reports the day before of shortages of the antiviral remdesivir in the UK, the Netherlands, Spain, and Poland. The EC agreed to buy 500 000 treatment courses in six months for €1bn (£0.9bn; $1.2bn). Though not all this money has been spent yet, 36 participating European countries (inside and outside the European Union) have collectively already purchased more than 640 000 vials, costing €220m. The countries’ volume of orders differs considerably, although under the agreement all have to pay €345 per vial, or on average €2070 for a course of treatment.
The deal was made just eight days before the World Health Organization’s Solidarity trial into potential treatments for people with covid-19 made public its interim results on 15 October. These showed that among patients in hospital remdesivir had no effect on mortality, length of stay, or need for ventilation.
Marie-Paule Kieny, a French virologist and member of the WHO Solidarity executive group, confirmed that Gilead was aware of the results. “WHO had an obligation to send Gilead the manuscript with the results before publication. This is standard practice, since the Solidarity trial was testing its molecule,” she told The BMJ.
Gilead acknowledged that WHO shared the Solidarity results with it in late September but said the manuscript was “heavily redacted, highly confidential, and incomplete.” However, a WHO spokesperson said that only information on other drugs was blacked out in the initial report, as is standard practice. Gilead declined to comment further about what was redacted. It said that it was not entitled to share the information about remdesivir’s poor performance in the trial with the EC before the results were made public on 16 October.
The journal Science reported that the EC was unaware of the results when it struck the deal with Gilead on 7 October.5 And an EC spokesperson confirmed to The BMJ that “the commission did not discuss this issue with Gilead prior to the publication of the preliminary WHO Solidarity trials.” However, Gilead said it had “heard” that the EC had been informed of the results before 7 October, through member states.
The company has aggressively disputed the Solidarity trial results, insisting that the safety and efficacy data for remdesivir “remained strong.”
Procurement process questioned
Brook Baker, professor of law at Northeastern University in Boston, believes the contract may have been poorly negotiated. “The question for the European Commission is: why did it not have a contract with Gilead with an escape clause based on the Solidarity trial outcome?” he said. “Regulators and authorities have an ongoing responsibility to ensure safety and efficacy.”
Critics urged the EC to at least revisit the deal when negative results emerged from the Solidarity trial.12 An EC spokesperson declined to comment on whether there were specific clauses in the contract, though another official said the framework does not allow for renegotiation.
Regulation in a pandemic
The case of remdesivir also raises questions about WHO’s regulatory processes in the context of a pandemic. WHO has a prequalification system that essentially assesses the quality and safety of potential products to allow countries to procure a drug or vaccine through the international supply system. But experts have questioned whether this process is sufficiently aligned with WHO’s clinical guidance.
WHO’s prequalification team approved remdesivir for listing on 15 October, the same day the Solidarity trial results were made public that showed its lack of effectiveness. And it took until 20 November to suspend the listing for remdesivir, only after WHO issued a “conditional recommendation against the use of remdesivir in hospitalized patients, regardless of disease severity.”13
A WHO spokesperson said the processes concerning prequalification and the Solidarity trials were strictly separated, to avoid conflicts of interest. The initial listing was based on the conditional approval given by the European Medicines Agency in July, the spokesperson added.
Baker said, “WHO’s prequalification team was apparently sitting there without being well connected to the wider WHO clinical guidance and to expert networks and advice. It is not clear why WHO went ahead and prequalified the drug, despite emerging evidence against its effectiveness. It uncritically accepted the conditional marketing authorisation by the EMA.”
By Lucien Hordijk and Priti Patnaik
The full article was published in the BMJ.
December 8, 2020