Genetic Therapy Inc., the Gaithersburg biotechnology company, and its parent, Sandoz AG, launched a pivotal, large-scale clinical trial yesterday of what the companies hope will prove a groundbreaking way to treat an incurable form of brain cancer -- gene therapy.
The companies said the trial involves 250 patients suffering from glioblastoma multiforme at 40 medical institutions in the United States, Canada and Europe.
There is a lot riding on the trial for Sandoz, the Swiss pharmaceutical giant.
If the trial is successful, Sandoz and Genetic Therapy could be among the first to show that gene therapy, which involves replacing or inactivating disease-causing genes at the cellular level, can work.
There is also a lot at stake financially for Sandoz.
The company paid $295 million last year to acquire Genetic Therapy and will invest an estimated $400 million to $600 million to develop and test the gene therapy for glioblastoma multiforme.
And Sandoz has staked at least part of its 21st century drug product pipeline on the emergence of gene therapy as a safe, effective treatment.
"We are hoping to make a very significant contribution to medicine with this therapy," said Dr. Stephen Marcus, vice president for clinical and regulatory affairs at Genetic Therapy.
Marcus said the company does not plan to show that the treatment cures brain cancer, but rather that it significantly slows its progression.
"Our goal is to provide a novel treatment that gives patients longer to live, and hopefully significantly improves their quality of life and their ability to work," he said.
The normal course of treatment for glioblastoma patients is surgery to remove the tumor, followed by radiation and sometimes chemotherapy. The disease usually begins progressing again eight to 10 months after surgery.
The therapy that Genetic Therapy and Sandoz have begun testing will aim to treat patients with an early-stage malignancy just after surgery to remove the tumor, Marcus said. It involves saturating the tumor cavity walls, where cancerous cells are almost always left behind and grow again, with a solution that contains a gene derived from the herpes simplex virus.
The gene is encapsulated in a mouse retrovirus that has been rendered harmless. The retrovirus has been found to attach itself only to cells that are dividing, which tumors cells do.
Patients are also given a shot of the anti-viral drug ganciclovir. The interaction of the drug and an enzyme produced by the herpes gene causes the dividing tumor cells to die off, or commit "suicide." Normal brain cells are not affected, Marcus said. It's for this reason that the treatment has been dubbed the "suicide gene" by some researchers.
Genetic Therapy found in an earlier study that the treatment did not cause herpes or any other viral infections in patients, Marcus said.
Dr. Dawn Willis, a virologist and scientific program director for the American Cancer Society, said the outcome of the trial will be closely watched because this type of gene therapy could have applications for treating other types of cancer that are localized, such as ovarian and early-stage prostate cancer.
Elizabeth Silverman, a biotechnology analyst and genomics expert with Punk, Ziegel & Knoell, an investment bank in New York, said the initial market payoff to Genetic Therapy and Sandoz would not be that large, if the brain cancer therapy was ever approved by regulators.
According to cancer experts, about 20,000 people in the United States and Europe die from brain cancer each year. That's about one-sixth the number who die from the leading cause of cancer deaths, lung cancer.
But, Silverman said, Genetic Therapy and Sandoz may have wisely targeted brain cancer to prove the effectiveness of its gene therapy, with an eye toward expanding its use into larger disease markets.
Because the disease is so fast moving and deadly, she said, people diagnosed with it usually die within 12 months. That so-called "end point" offers the companies an opportunity to gather data on the gene therapy in a period that will not be financially prohibitive. Testing the therapy on other cancers, some of which can last for years, might be hugely expensive.
A Sandoz spokesman, Harry Rohme, said the company had not determined what the gene therapy would cost. But Silverman, the analyst, said most experts believe such treatments will cost more than $30,000.
Pub Date: 9/19/96