Paris

The recent difficulties faced by gene-therapy trials in the United States seem to have had little impact on attitudes to the regulation of such trials on the other side of the Atlantic.

This was the prevailing sentiment at a meeting of European scientists, regulators and industrialists involved in gene therapy, held in Paris last weekend. Indeed, several delegates deplored what they described as the excessive secrecy of European approval procedures for gene therapy.

The meeting was organized by Euregenethy, a grassroots network of scientists and physicians keen to promote gene therapy and the harmonization of regulatory laws across Europe.

The current plethora of national committees and rules is widely seen as a hindrance to clinical development, providing less clarity and concentration of expertise than would a single pan-European procedure, and making it more difficult to organize the large trials needed to assess safety.

Speaker after speaker told the meeting that Europe's handling of gene therapy is anything but harmonized. Although new drugs are approved by the London-based European Medicines Evaluation Agency, national governments must approve clinical trials. Only the United Kingdom, France, the Netherlands and Italy have dedicated systems for gene therapy in place.

In all countries, approvals depend on several different committees. Mark Richardson, head of regulatory affairs at Orio clinical services in Slough, UK, said that in such multi-stage reviews, the division of responsibilities between scientific, ethical and regulatory bodies is often unclear. As a result, approvals face long delays, and criteria for approval are unclear and differ from country to country.

The main organizer of the meeting, Odile Cohen-Haguenauer of the St Louis Hospital in Paris, is working on gene therapy for Fanconi anaemia, a rare childhood disorder. Despite progress in the laboratory, a multinational clinical trial will be “extremely difficult” to set up in Europe, she says.

Ted Friedmann, director of the programme in human gene therapy at the University of California, San Diego, and a member of the US Recombinant DNA Advisory Committee, said the meeting had taught him the “political realities” of the complexity of European regulation. Whatever the recent failings of the US system, he said, it was at least “linear”, and gave “much less opportunity for confusion”.

Friedmann also said that if there was a lesson for Europe from the US controversy, it was of the need for building “openness” into regulatory structures: ”over the last year we have learnt that open review is better than closed” (see Nature 405, 606– 607; 2000). A marriage had to be found between legitimate industrial confidentiality “and the need for the public to know what happens”.

Following the death of Jesse Gelsinger during a clinical trial run by the University of Pennsylvania's Institute for Human Gene Therapy in which high doses of adenoviral vector particles were given, Euregenethy has been carrying out a survey on the use of such vectors in Europe. It has found that many of the 30 ongoing or finished clinical trials have used them, some in similarly high doses.

Trials of the systemic application of adenoviral vectors have been put on hold by scientists themselves following Gelsinger's death, according to Euregenethy, while various European countries have begun to assess the safety of trials that have used adenoviral vectors.

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