Introgen seeks FDA approval for 'groundbreaking' cancer drug

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Introgen seeks FDA approval for 'groundbreaking' cancer drug

By Lilly Rockwell

AMERICAN-STATESMAN STAFF

Tuesday, July 01, 2008

An Austin biotechnology company on Monday became the first to apply for U.S. Food and Drug Administration approval of a gene therapy drug to treat recurring head and neck cancers.

But it could be early 2009, at best, before Introgen Therapeutics Inc. gets a decision on whether it can market the drug, Advexin, on which it has been working for 14 years.

Introgen also is seeking approval to market Advexin in Europe.

Approval could produce a bonanza for Introgen, which has been surviving for years on stock sales, slender contract revenue and the patience of investors who understand that drug development takes years.

Advexin is designed to attack cancers that are especially hard to treat with other therapies, and the company is researching other potential applications.

Experts say what Introgen has accomplished is groundbreaking because Advexin is the first gene-based drug to get this far.

"It's a major milestone for gene therapy, because it's a first-in-class drug," said Stephen Dunn, an analyst with Dawson James Securities. Introgen has requested a priority review for Advexin. If the FDA grants that designation, it could make a decision in as little as six months. Without priority review, a decision could take about a year.

Advexin works by using a deactivated cold virus to insert the p53 tumor suppressor gene into cancer cells. That restores the normal function of p53 and helps restore healthy cells while killing cancerous ones. Studies show that Advexin works only on patients who have low levels of the p53 gene. About two-thirds of the head and neck cancer patients studied in clinical trials were able to take the drug.

Cancer is caused by a defective gene, said Robert Sobol, Introgen's senior vice president of medical and scientific affairs. "When you are able to provide and deliver into the tumor the correct gene function that is missing or defective, that is treating a disease at its most basic and fundamental level."

Sobol said Introgen is confident that its data from Phase II and Phase III clinical trials will bolster its case that Advexin is effective. The drug "really addresses the needs of patients that have significant and dire needs," Sobol said.

Advexin has the potential to treat other types of cancers, including breast and lung cancers, but the applications filed Monday are only for recurrent head and neck cancers. About 40,000 Americans are diagnosed each year with head, neck and throat cancers.

Introgen was founded in 1993. It licensed technology developed by Jack Roth, a researcher at the University of Texas M.D. Anderson Cancer Center in Houston. UT and Roth are part-owners of the company.

Introgen actually began the FDA application process in 2004, under a special program that allows developers of certain drugs to file their applications in phases. But there have been several delays in completing clinical trials, which slowed the process.

The average drug development cycle, from inception to market, is 10 to 15 years, according to the Pharmaceutical Research and Manufacturers of America. It can cost more than $1 billion to develop a drug such as Advexin.

Advexin is Introgen's flagship drug and the one that is furthest along in the development process. Approval of Advexin would open the door for approval of Introgen's stable of gene therapy drugs.

But it's unclear whether the FDA will be inclined to approve Advexin. The federal agency has faced considerable scrutiny in recent years for approving drugs that produced dangerous side effects, and it has become more cautious as a result. Last year, the agency approved 19 new drugs, a 24-year low, according to the Wall Street Journal.

"The FDA is the moving target," Dunn said. "On the plus side ... the FDA has raised the hurdle for safety."

Advexin has a good safety record, Introgen analysts say, with mild side effects that produce flulike symptoms. It can be used in concert with chemotherapy and radiation.

Investors celebrated Introgen's filing, sending the stock up nearly 3 percent to close at $1.55 Monday. The company's shares have fallen 47 percent in the past six months.

If Introgen doesn't gain approval for Advexin, it would be a huge blow but wouldn't necessarily spell the end for the company, said Canaccord Adams analyst Joseph Pantginis.

"They have a very broad and deep pipeline. But at the same time, they are coming into tight times in regard to financing," Pantginis said. "It's very rare to see biotechs go completely under. They always find a way to survive."

lrockwell@statesman.com; 445-3819

What is gene therapy?

It's a new treatment that involves introducing genetic material into a person's cells to fight or prevent a disease, such as cancer. A gene can be delivered to a cell using a carrier, such as a virus.

How does Advexin work?

It uses a deactivated cold virus to insert the p53 tumor suppressor gene into cancer cells. For most people with cancer, p53 is inactive, at low levels or mutated, making it easier for cancer cells to flourish.

How would the FDA approval process work?

Introgen has asked for priority review, which could mean a decision by early 2009. Without that status, it could take closer to a year.

An FDA review committee will examine the clinical trial results, looking at the sample size of the trial and the safety and efficacy of the drug.

Sources: Introgen Therapeutics, National Cancer Institute

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