NEWS

Gene Therapy in Europe: New Initiatives Seek Streamlined Debate

John Illman

While gene therapy protocols recently have come under close scrutiny in the United States, gene alteration in general is a politically charged issue for much of Europe. Two recently announced initiatives—one in the United Kingdom and one Europe-wide—aim to streamline debate and may potentially have a major influence on human gene therapy in Europe.

Last May, the U.K. government appointed a Human Genetics Commission that will meet for the first time in February. According to a press release from the U.K. government, the commission will "analyze current and potential developments in human genetics and advise ministers on their likely impact on human health; and on their social, ethical, legal, and economic implications."

The commission is also taking over the responsibilities of three other regulatory bodies—the Advisory Committee on Genetic Testing, the Advisory Group on Scientific Advances in Genetics, and the Human Genetics Advisory Commission.

Public Debacle

Hilary Harris, M.D., a general practitioner in Manchester, England, with a special interest in gene therapy, said she thinks the government wants to avoid a public debacle similar to the controversy that erupted about genetically modified food.



View larger version (138K):
[in this window]
[in a new window]
 
Dr. Hilary Harris

 
"They felt that they needed to get a single focus of advice that was going to speak with more clarity and authority than perhaps a number of different groups were able to do," Harris said.

The commission will be headed by Baroness Helena Kennedy, one of Britain’s most powerful and persuasive women. A criminal lawyer who has been involved with some of the major trials of the last 10 years, Kennedy is also the chancellor of Oxford Brookes University, Oxford, England, and sits on the advisory council of the World Bank Institute.



View larger version (141K):
[in this window]
[in a new window]
 
Baroness Helena Kennedy

 
One of the first messages Kennedy may take to health ministers is that scientists working in gene therapy believe that they are faring poorly compared with their European and U.S. colleagues. Regulations governing gene therapy research in Britain are said to be the most stringent in Europe—and considerably more stringent than those in the United States.

George Dickson, Ph.D., of the department of molecular cell biology at the University of London, said that there is a tremendous difference among different countries in the European Union in terms of quality and control. "There’s a very strong case for developing a ‘best practice philosophy’ across the European Union," he said.

But Dickson said he fears that the U.K. regulations may be too restrictive and threaten progress. "I think it is noteworthy that in the U.K. there are very few, if any, gene therapy trials using viral vectors for gene transfer. This is a reflection of the perceived hurdles and difficulties getting into the clinic.

"There are a small number of biotechnology companies developing gene transfer based platforms. But how many of the larger pharmaceutical companies in the U.K. are showing a commitment to gene therapy?"

Dickson’s sentiments were endorsed by a senior executive working for one of Britain’s leading biotechnology companies. Asking to remain anonymous, he declared: "I’m going to make sure I have opportunities in the U.S. I’m not having our commercial success constrained by regulatory processes in the U.K." The London-based Gene Therapy Advisory Committee, which is responsible for assessing gene therapy research protocols, was "far more cumbersome," he said, than the U.S. Food and Drug Administration.

Unified Regulations

On a broader scale, the Paris-based Euregenethy network—an organization of European gene therapists—is campaigning for harmonization of gene therapy regulation to promote safety and international exchange of knowledge. The need for harmonization was highlighted by a 1999 Euregenethy report in which representatives from 15 member states were asked to contribute to a report summarizing the regulation of gene therapy in Europe. The results highlighted "a high level of heterogeneity," said Odile Cohen-Haguenauer, M.D., Ph.D., the coordinator of the network.

There was, it emerged, no legal definition of gene therapy in Belgium, while a definition was being drawn up in Norway. In Portugal, there were no regulations or laws governing gene therapy. In Denmark, there was no central agency specifically responsible for dealing with issues involving the transfer of genetic material. Following a public and parliamentary debate, the Danes decided that "existing legislation was flexible enough to encompass these issues as well," the report said.

In Germany, gene therapy and somatic cell therapy used in vivo were classified as "medicinal products." In France, gene therapy is regulated under a specific law; and gene therapy products are defined as anything used to transfer genetic material for therapeutic, diagnostic, and prophylactic purposes.

At least four bodies have to approve a gene therapy protocol in France. Cohen-Haguenauer noted that the French have a very demanding regulatory system, "but no accidents have been reported so far in France even though a high number of protocols are carried out here," she said.

Demanding System

"I know that people have criticized the French system—[mostly] French people—but I don’t think it’s justified. What happened in the U.S. would not have happened here," she said in reference to 18-year-old Jesse Gelsinger, who was the first person to die in a gene therapy experiment (see News, Jan. 19, 2000). Gelsinger was one of an estimated 3,000 patients to have received gene therapy over the last 10 years.

According to one estimate, between 120 and 150 gene therapy trials are in process in Europe, with cancer trials accounting for about 70% of the total. This compares with a total of 357 in the United States, of which 218 involve cancer. The European trials are predominantly phase I and phase II, and the U.K., France, and Germany stand out as the premier European research centers, accounting for more than half the total number of European gene therapy trials.

Fields Not Level

How do they compare with the United States? The feeling in France is that the playing fields are not level. Bernard Escudier, M.D., of the The Institut Gustave Roussy, Villejuif, France, is one of many European investigators studying the p53 tumor suppressor gene that is so often mutated in common tumors. There were, Escudier said, far more restrictions on the use of p53 in France than in the United States.

"The U.S. model is a good model for the patient," Escudier said. In June, Euregenethy is staging a multidisciplinary forum to discuss European regulations and the safety implications of novel technologies under development. This will follow an earlier meeting attended by European Union officials, scientists, and civil servants with a responsibility for gene therapy.

But the ultimate test for Europe will be the number of cancer gene therapy products that reach the marketplace. Alan Kingsman, Ph.D., formerly a professor of biochemistry at Oxford University, formed Oxford Biomedica as a biotechnology company in 1996. It has quickly established itself as one of Europe’s leading biotechnology companies.

"I feel very optimistic," Kingsman said. "I’m sure the first products will be out within a few years. We’ve had genetic manipulation since the late ’70s. If you look back at the commercial predictions, you will see that they have not been realized. The research has been successful, but not so successful as it might have been."

Solve Most Problems

And Kingsman also said he thinks that gene therapy will solve most of the problems involved with commercializing recombinant DNA technology, such as production issues, administration, and pharmacokinetics.

"The big limitation, as everyone knows, has been the efficiency of gene transfer in vivo," Kingman said. "But with the new systems, this limitation is going to go. Like anything else, gene therapy will start small with products aimed at late-stage disease."



             
Copyright © 2000 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement