Fighting Back: New Drugs Help Recharge the Immune System  

Christine Miller Ford
Special to Washington Techway
Wednesday, August 7, 2002; 7:45 AM

Scientists at biotech companies across the region have begun to employ cancer patients' own immune systems to deliver powerful, personalized treatments and better boost the body's defenses.

Immunotherapy, in which drugs enhance the body's ability to fight off disease, has its roots in the molecular biotechnology research that began in the 1960s.

But only a handful of treatments are on the market, notably interferon and IL-2, both approved by the Food and Drug Administration to treat some types of cancer, including melanoma and kidney cancer. Side effects can include malaise and other flu-like symptoms.

The number of such drugs remains small because their development is labor-intensive and the field itself is still developing, according to the FDA Center for Biologics Evaluation and Research. FDA officials don't track how many immunotherapy drugs are being tested across the country, said FDA spokeswoman Kathleen Kolar.

Cancer poses a formidable target for the region's biotechs. More than 550,000 people died of the disease in the United States last year; doctors diagnosed 1.2 million new cases.

Drug companies must spend more time and more money to prove a drug works, said Jeff Trewhitt, spokesman for the D.C.-based trade group Pharmaceutical Research and Manufacturers of America. "In 1980, the average time it took for a drug to move from clinical trials to market was three to four years," he said. "Today it's six to seven years."

The cost of getting a single drug from clinical trials to market has skyrocketed in the past two decades, Trewhitt said, from $259 million in the mid-1980s to today's average of $800 million.

Trewhitt cites a number of factors for the changes, including greater regulatory requirements from the FDA as well as pressure from managed health groups, which account for 60 percent of the market for drugs, to justify new treatments.

At Gaithersburg biopharmaceutical company GenVec, the drug gene TNFerade is seen as "extremely promising" in destroying cancer cells outright and jump-starting the immune system, said Dr. Henrik S. Rasmussen, the company's vice president for clinical and regulatory affairs.

"We're able to deliver a very powerful anti-cancer agent directly to the tumor," said Rasmussen, who explained that TNFerade not only cuts off blood supply to the tumor, starving it, but also reprograms the tumor to begin attracting white blood cells designed to police the body and destroy foreign substances.

"We don't know why, but the T-cells typically do not attack cancer cells," Rasmussen said. "This drug gets them to do what they should be doing."

In GenVec's recently announced Phase I trials, tumors grew smaller in 76 percent of the 21 patients evaluated and none of the patients reported any harmful side effects, Rasmussen said.

"It's virtually unprecedented," said Rasmussen, who also holds a Ph.D. "This was among patients who had failed chemotherapy, radiation and every other treatment. These are people who were at death's door."

Phase I trials evaluate a drug's safety to humans; in Phase II's randomized trials, scientists measure the drug's effectiveness by comparing patients in a control group to patients taking the drug.

The number of volunteer patients involved in the average clinical trial has more than tripled, from 1,300 in 1983 to 4,500 today, Trewhitt said. Scientists conducted 30 technical studies in an average clinical trial in 1983, he said. "Today, the average is 68," Trewhitt said.

Collectively, the pharmaceutical industry spent $30.3 billion on drug research and development in 2001 - up from $2.7 billion in 1980. "There's a sharp increase in the total amount spent," Trewhitt said. "The cost of research is skyrocketing."

Another reason for the spending jump, Trewhitt said, is the learning curve necessary as pharmaceutical companies move from their research from traditional chemistry to biotech's natural proteins. "They're spending more time and more money on basic research," he said.

Most drugs that enter human clinical trials never earn the FDA's approval. "Four of five are discarded, with absolutely no return on the investment," he said. "A company can lose millions of dollars on a single idea."

Predicting the potential financial value of TNFerade is difficult, said Jonathan Aschoff, senior analyst with Friedman, Billings, Ramsey & Co. "We would want to see how the drug performs in Phase II (first)," said Aschoff, who foresees the results of that trial coming late next year.

The drug may take five years or longer to come on the market in the United States, Rasmussen said. "The FDA needs to see that this drug helps patients live long and feel better," said the doctor, who joined GenVec in 1999. "We have no doubt that we'll be able to show that."

OncoVax is a new immunotherapy for colon cancer from Intracel, the biopharmaceutical company in Frederick. The drug relies on cells taken from a patient's tumors to ward off a reoccurrence of the disease.

"It's a very different model," said Peter Nardin, the company's chief operating officer. "For years and years, pharmaceutical companies have made pills that are the same for you, me and a million other people. With this, doctors remove your tumor, deliver it to us for processing and we create a drug that uses your own immune system to recharge your immune system."

Nardin said the drug, injected into each limb over six months, offers no serious side effects, only a mild reaction that's similar to the redness produced by a smallpox vaccination. More than 1,200 patients from the United States, Holland and Belgium took part in the study, which began in 1987.

Won't a personalized drug cost a fortune? "It's not expensive when compared to the alternatives," Nardin said. "When colon cancer reoccurs, there's really no treatment other than surgery or chemotherapy. There's no question OncoVax would be cheaper than that."

The drug, already marketed in Holland, Germany, Austria and Switzerland, will be submitted to the FDA later this year after Intracel reworks its manufacturing process. "We realized we needed to produce a sterile vaccine," said Nardin, whose company also is working on immunotherapies for head and neck cancer and ovarian cancer. "No one was thinking about a sterile vaccine when we began this process 14 years ago."

Officials with Gaithersburg-based Digene say their new, liquid-based Pap test may help prevent cancer, said spokesman Al Fleury. Next month, Digene plans to the FDA an updated test that detects human papillomavirus, or HPV, a component of more than 99 percent of cervical cancers.

"With the current test there's a large gray middle, where a patient's cells do look different but it's not clearly cancer," said Fleury, who explained the standard followup to such an inconclusive Pap is to repeat the test every three to six month until tests come back normal twice in a row. "There's a lot of anxiety there. You're thinking for two years that you might have cervical cancer."

Digene's test, which would give a patient her results in a day or two, would provide peace of mind quickly and could replace the current Pap test as the standard primary screen.

"A patient would know that no, she does not have the virus and isn't at risk for cervical cancer or that HPV is present and more invasive followup is needed," Fleury said. "Rather than spending time and money testing and retesting, we could concentrate our medical resources on the women where we'll find 100 percent of the cancers."

Christine Miller Ford is a freelance writer.

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