- The Washington Times - Wednesday, January 26, 2000

Recent discussion among National Institutes of Health (NIH) officials over gene therapy research has raised concerns about the slow progress of this breakthrough medical treatment.

Some critics scoff at the lack of evidence for gene therapy's efficacy 10 years after the first clinical trial was conducted. Are patients and the public being mislead? Some perspective may help explain why the answer to that question is a resounding no.

Gene therapy is on the drug development frontier, not unlike two other biotechnology medicines that generated great excitement two decades ago interferons and monoclonal antibodies.

In the 1970s and 1980s interferons and monoclonal antibodies were touted as wonder drugs against a range of diseases, particularly cancer, because of their stunning success in laboratory experiments. Both were tagged "magic bullets." These bullets, however, were blanks initially because of difficulties in getting them to reach their targets in humans.

After years of research, interferons were first approved in 1985 for hairy cell leukemia. During the next 15 years, as research progressed, these natural human proteins emerged as effective treatments against a whole range of viral diseases and cancers, including melanoma, lymphoma, hepatitis and multiple sclerosis. The discovery of therapeutic applications for interferons is far from over.

Monoclonal antibodies also were a disappointment after being touted for their extraordinary cancer fighting abilities. It took almost 20 years to figure out how to get them to work in humans. The first antibody drug for cancer finally was approved for patients in 1997 for non-Hodgkin's lymphoma. Since then antibodies have proved effective for breast cancer, inflammatory bowel disease and respiratory viruses in children. Antibodies in development target an even broader range of diseases, from asthma to leukemia to prevention of organ transplant rejection.

The years of persistence, dedication and investment of biotechnology companies are paying off for the millions of patients who benefit from interferons and monoclonal antibodies.

This same scenario eventually will hold true for gene therapy, which uses genes, or DNA, to intervene against illnesses. Gene therapy is emerging as an effective medical strategy not only to counter the molecular causes of diseases, such as cancer, cystic fibrosis and hemophilia, but also to tap into in our cellular mechanisms to enlist their help in fighting other ailments, such as growing new blood vessels as a substitute for heart bypass surgery.

Gene therapies, however, are still in early clinical trials. Methods of administration are being studied as are dose levels and combinations with other drugs. The vectors, or delivery vehicles, used to insert the therapeutic DNA into cells also are being refined, and identifying patients who will benefit from the treatment is key. This cautious pace is standard practice in drug development.

The current second-guessing about gene therapy, however, has another element. It followed the tragic death of a patient in a University of Pennsylvania clinical trial. The heartbreaking loss of 18-year-old Jesse Gelsinger, of Arizona, rightfully has raised questions about the clinical trial in which he participated.

But perspective is needed here also. Gene therapy is subject to greater oversight than virtually any other medical technology. In addition to the U.S. Food and Drug Administration (FDA), which has regulatory authority over all drug development, the NIH's Recombinant DNA Advisory Commission (RAC) reviews, in a public forum, protocols of gene therapy clinical trials.

RAC's role is to discuss publicly the social and ethical implications of gene therapy. It complements the FDA's regulation of the safety and efficacy of treatments.

The FDA is responsible for clinical trial safety. It closely monitors studies and has the power to take action if regulations are violated. Its investigation of the University of Pennsylvania patient death, for example, has revealed lapses in safety protocol rules.

The extra review of clinical trials by RAC is not mandatory, but biotechnology companies enthusiastically comply because they recognize the need for public debate on new technologies.

To better assist the RAC in its mission, the biotech industry also has proposed giving the advisory panel more information on patient safety during clinical trials. Our companies have agreed to supply RAC with the same information given to the FDA on serious adverse patient events at the same time and in the same format.

However, we do not favor creating a redundant regulatory agency at NIH. Such a move would severely impede the progress currently being made in gene therapy.

Despite the early frustrations, our companies are committed to spending the time and money to bring gene therapy to patients. We believe gene therapies will work.

We are also committed to advancing cautiously and safely. Anything less would be a gross disservice to the patients we are trying so hard to help, an abandonment of our own principles and a clear violation of the established regulatory framework.

Carl B. Feldbaum is president of the Biotechnology Industry Organization.

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