Pain drug development booming, reports anesthesiologist

The number of new drugs being developed to relieve neuropathic pain – a chronic, devastating condition affecting three to eight per cent of the population – has quadrupled over the past year and a half, a Queen’s University study shows.

But under present regulations, pharmaceutical companies are not required to test their products against currently used neuropathic pain drugs, notes Dr. Ian Gilron, Director of Clinical Pain Research for Queen’s Departments of Anesthesiology, and Pharmacology & Toxicology, and an anesthesiologist at Kingston General Hospital. “We would like to see more comparative drug trials, whenever possible, so that the increased value of new drugs is clearly shown.”

His review, co-authored with Dr. Terence Coderre of McGill University, will be published in the March 2007 issue of the journal Expert Opinion in Emerging Drugs.

“We were surprised to discover how rapidly this area has mushroomed in a period of less than two years,” says Dr. Gilron. His survey of recent submissions to Investigational Drugs (IDdb) and Pharmaprojects databases revealed that the number of new drugs under development to treat neuropathic pain has jumped from 13 to 48.

Defined as “pain caused by a lesion of the nervous system,” neuropathic pain is a condition that has puzzled health care workers for years because it is often experienced in areas of the body that appear to be uninjured. Generally longstanding, severe, and resistant to over-the-counter painkillers, it may result from a wide variety of causes, including degenerative spinal disease, diabetes, cancer and infectious diseases that affect the brain, spinal cord and/or peripheral nerves.

“What’s particularly exciting is the emergence of entirely new types of drugs to combat this unique pain condition,” says Dr. Gilron. “With so much work in basic science happening today, and the recognition now that this is such a prevalent public health problem, scientists in both universities and industry are able to apply the new knowledge.”

Traditionally, the drugs used to treat neuropathic pain have been anti-depressants, anti-convulsants, and sometimes opioids like morphine. On average they reduce pain intensity by 20 to 40 per cent.

New developments now under way include:

· vanilloids, such as capsaicin, extracted from hot chili peppers, that actually burn when applied to the skin and eventually exhaust the nerve’s ability to transmit pain;

· cannabinoids, derived from chemical components found in marijuana or cannabis; and

· combinations of drugs, where the combined effect is better than either drug, when used alone.

Still in an experimental stage are pain-inhibiting treatments derived from gene therapy. “We’re not aware of any clinical trials in this area, but the scientific basis is certainly there,” says Dr. Gilron, noting that his study captured only those drugs disclosed in the public domain. Industry is not required to make public its pre-marketing testing, as long as other regulations are being met.

Of the new drugs identified in the review, 10 were in Phase I clinical trials (testing for toxicity and tolerability); 30 were in Phase II trials (looking at effectiveness in a target population); and eight had entered Phase III (the “pre-marketing” stage which is usually much larger and placebo-controlled).

“Although it’s likely that only a handful of these drugs will be on the market in less than five years, it indicates there’s a lot of potential, and that the pipeline is getting fatter!” says Dr.Gilron. The fact that regulatory agencies currently don’t require such clinical trials to include “active comparators” (determining whether the drug being tested works better than those already on the market) makes optimal treatment selection more difficult for prescribing doctors, he comments.

The study recommends that, whenever possible, drug trials should include comparative evaluations throughout the development process.

Nancy Dorrance, 613.533.2869, nancy.dorrance@queensu.ca, Lorinda Peterson, 613.533.3234, lorinda.peterson@queensu.ca, Queen’s News and Media Services