FDA approval of Botanical drugs

Dueling Therapies:
Is a Shotgun Better
Than a Silver Bullet?

By NICHOLAS ZAMISKA
WSJ March 2, 2007; Page B1

HONG KONG -- Chinese doctors have long experimented with combinations of herbs to cure disease. If a plant extract helped to fight an infection, why bother trying to figure out which molecule did the trick? It worked, and that's what counted.

By contrast, the U.S. Food and Drug Administration, one of the world's most stringent drug watchdogs, for decades has looked askance at most herbal medicines. The focus in Western pharmacology is finding the single molecule that cures a disease. Pharmaceutical companies such as Pfizer and Merck spend billions of dollars combing through huge libraries of compounds to find the elusive blockbuster therapy.

The two approaches boil down to a simple question: Is it better to attack disease, as the Western world does, with a silver bullet -- the one substance whose potency has been pinpointed? Or should treatments be administered, as the Chinese method dictates, by aiming a group of agents at the problem -- the shotgun approach?

The FDA has long held botanical drugs to the same standard as other therapies: Companies applying for regulatory approval had to find the part that works and prove it. That requirement has relegated most Chinese medicines and other plant-based, or botanical, therapies, such as ginkgo and Echinacea, to the dietary-supplement shelves at supermarkets and kept them out of U.S. pharmacies.

But recently, the agency's policy has evolved into one that is more accommodating to the Chinese approach. In June 2004, the FDA issued new guidelines making it easier for drug companies to turn herbal remedies into Western medicines. And late last year, the FDA approved its first botanical drug under the new system, an ointment for genital warts called Veregen, made from green-tea leaves. The treatment was developed by MediGene, a company with headquarters near Munich, Germany.

In the new guidelines, the FDA for the first time spelled out explicitly how companies could submit for approval botanical extracts -- emphasizing that further purification wasn't required and that there was no need to identify a single active ingredient. Standards for human clinical testing, however, remained the same as for all drugs.

"There were so many stories of potentially new treatments in alternative medicine ... we needed a different approach than dealing with a single small molecule," says Shaw T. Chen, the botanical team leader at the FDA.

This new openness has led to a surge of applications for approvals. Some 250 botanical drugs have since been cleared to proceed to clinical trials.

The FDA even established a special office to deal with all those applications. To help run it, the agency hired experts with training in herbal medicines. Jinhui Dou, for instance, a drug reviewer for the FDA's newly formed botanical review team, was born in China and has a degree from the Beijing University of Chinese Medicine.

It's hard to predict how many other traditional remedies from foreign cultures may someday be presented to the FDA. Chinese medicine encompasses a vast variety of treatments -- like dried deer penis pulverized and taken as tea. The FDA says it still is helpful for applicants to identify active ingredients and how they might work, because that can help predict dangerous side effects.

Proving the effectiveness of these therapies is still a big challenge for the manufacturers. "Overall progress has been slow," Dr. Chen says.

One company that is aiming to beat the odds is Phynova, a small British drug-research concern that has the green light from the FDA to test a hepatitis botanical drug. The drug is a combination of four different plants: the roots of the astragalus and the Chinese salvia plants, the fruit of the schisandra plant, and milk thistle. The hope is that they will all work synergistically to combat the symptoms of chronic hepatitis.

The number of chemical compounds contained in each of those distilled extracts could vary from several hundred to more than a thousand. It may be that many of those are working on a variety of levels. The advantage of such an assault on multiple targets is that human bodies, and the pathogens that try to invade them, have many redundant backup systems -- like a generator that turns on when a fuse blows.

Some proponents of herbal therapies are convinced that the more shots fired at a disease, the better -- an approach to which the new FDA guidelines now give more weight.

"There's a theoretical possibility that there are multiple active ingredients in botanicals that act on multiple systems that have synergistic effects," says Dr. Chen. "But that remains to be proved."