Life-saving drug hits eurocrat wall - a Kafkaesque tale
13.02.13 @ 15:53
BRUSSELS - A French medical laboratory and the European Commission are currently locked in a furious legal battle - at stake is whether a handful of EU civil servants, through use of byzantine rules, can defy medical opinion and keep a life-saving drug off the market.
The battle has been going on for three years.
The eventual court judgement will directly affect patients with a very rare genetic disease. More broadly, it will define the boundaries within which commission officials can play around with internal rules to achieve a result they alone want.
The dispute concerns whether to give a drug called Orphacol an EU-wide market authorisation.
The drug is used to treat two forms of liver disease - 3 Beta HSD deficiency and Delta 4-3-OxoR deficiency - so rare that they do not have colloquial names. There are an estimated 90 patients at most in Europe. Ophacol's positive effects are undisputed.
"Patients basically go from being fatally ill with the only therapeutic option being a liver transplant to being completely normal human beings with no signs of the disease," says Andreas Vogel, regulatory director at CTRS, the small French laboratory that made the EU market application.
The story goes back 20 years. In 1993 it was discovered that cholic acid, a type of bile acid produced by the liver, helped to combat the disease. Without treatment the condition is fatal. In 2007, Paris's public hospital system, which discovered and subsequently managed the medicine, decided to hand over the rights to the CTRS lab.
CTRS, run by Antoine Ferry, gave the medicine the name Orphacol and obtained a special licence from the French medical agency. Orphacol is now being used to treat 22 patients in France - 17 French, two Swiss, one Italian and one Portuguese.
In 2009, Ferry decided to apply for EU-wide market authorisation. Just over a year later, the European Medicines Agency (EMA) in London voted unanimously in favour of the idea.
Power to actually authorise a product for the EU market lies with the European Commission. It is normally easier to get regulatory approval for a so-called orphan drug, which treats rare conditions. And it was among the rarest diseases ever dealt with by the EMA.
The legal odyssey
Yet here is where CTRS' as-of-yet fruitless odyssey began.
To date the only result Ferry and Vogel have to show for their efforts is an impressive grasp of comitology - how legal decisions are made at committee level in the European Union, a process reminiscent of the surreal stories of Czech writer Franz Kafka.
The European Commission, and specifically the human-use drugs unit in the commission's health directorate, asked the EMA to better justify its positive stance. The agency in 2011 confirmed its original opinion and emphasised that Orphacol is of distinct public interest.
A commission decision should have come around two months later. But the commission was still not happy.
The French lab lacked clinical trial-based evidence, it said. And, continuing to cite chapter and verse of the rules, it argued the company was therefore not entitled to apply for market authorisation under exceptional services.
Clinical evidence, says CTRS, is impossible given the degenerative nature of the disease.
"A controlled clinical trial would have meant taking some people off the medicine." says Vogel. "The alternative - comparing a new patient before and after treatment - is not feasible because there are so few patients. In December 2012 we identified the first new patient in France since 2007. So you can't plan for a clinical study."
In July 2011, the commission decided to reject the authorisation.
Member states' experts disagreed and voted down the commission decision. But the commission was not deterred. It appealed the decision. The appeal committee, again with member states' experts, rejected the commission's position once again.
With the second rejection, the whole process moved into uncertain legal territory.
The rules are unclear at this stage, saying only that the commission cannot adopt its original decision - the rejection of market authorisation of Orphacol.
For a while nothing happened. The French laboratory pressed for a decision. But the then health commissioner John Dalli wrote back to say that the commission will neither approve or disprove market authorisation, creating an unhelpful status quo.
Ferry then decided, in January 2012, to bring the commission to court for failure to act.
A hearing was due in April but at that point the commission sent a third proposal for refusal to member states.
This time, the meeting of member state experts fell on a public holiday. Some member states were missing and the required qualified majority needed to reject the commission's latest rejection was not reached.
Finally the commission had the result it wanted - it rapidly adopted a decision to reject market authorisation for Orphacol.
The highly unusual manoeuvre - coming in the midst of legal proceedings at the EU court in Luxembourg - also meant that the failure-to-act premise of Ferry's case collapsed. The judges, irritated by the commission's antics, ordered the Brussels bureaucracy to pay for CTRS' costs.
Member states alarmed
The French laboratory is now in the process of taking the commission to court again.
This time they have the support of a handful of member states, alarmed at what they see a precedent-setting case for abuse of power by EU civil servants. They want legal clarity.
"We are taking the commission to court on the merits of the case and on the comitology procedure," says CTRS' Antoine Ferry. "We want to know if it is possible to reintroduce a draft decision as often as the commission wants until it gets the decision it wants."
For its part, the commission argues that it cannot loosely interpret market authorisation rules for one product as this would set an example for the future.
"This case is not about a formalistic interpretation of the law disconnected from public health," says Frederic Vincent, the commission's health spokesperson.
"It is the first time that such an application is ever submitted and the commission considers that lowering the requirements is not in the interest of public health."
A court decision is due later this year.