Most major drug companies gave up their work on analgesics several decades ago because no progress had been made in finding a replacement for morphine.
Four years ago, Nelsen and Arch helped put together a company that would focus on opiate analgesics in a new way. Arch, a venture firm with $150 million under management, obtained the licenses to newly cloned pain receptors from the brain, and went looking for someone to head the company, called Adolor Corp. (Dolor means pain; adolor means absence of pain.)
They found John J. Farrar, microbiologist, immunologist, and former senior vice president at Sterling Winthrop in Upper Providence, Montgomery County.
``I always thought analgesics was a great place for a small company,'' said Farrar, who joined the Malvern company in 1994 as president and chief executive. While there are a lot of drugs on the market, big pharmaceutical companies aren't investing much in analgesic research. That means lots of opportunity and less risk, he said.
Led by Arch, Adolor has raised $20.8 million to finance its research and development program. Seven major investment firms have invested in Adolor, including TL Ventures of Wayne, S.R. One Ltd. in Wayne, and Weiss, Peck & Greer Venture Partners in San Francisco.
Another advantage to studying analgesics is that the clinical trials are short and relatively inexpensive, which means that compounds should be able to move to market more quickly. On average, the drug industry estimates, it takes up to 12 years and costs more than $200 million to bring a drug to market.
Effectiveness of analgesics is measured in hours or days. In contrast, one clinical study Farrar oversaw at Sterling for a heart medication involved tracking 20,000 patients and took four years to complete.
Currently, there are two classes of analgesics available: narcotics (such as morphine), which are used for severe pain, and non-steroidal anti-inflammatory drugs (such as ibuprofen), for mild to moderate pain.
The market for drugs to ease pain is large. Retail sales of pain-management analgesics totaled $11.8 billion in the United States in 1995. That is expected to grow to $18.8 billion by 2000, according to the Find/SVP research service.
The holy grail of analgesic research would be to find a drug that would eliminate the side effects caused by morphine, including respiratory depression, nausea and addiction. That is central to Adolor's long-term research, which has been made possible by advances in understanding of the opiate receptors in the brain.
In the late 1980s, university researchers decoded the genetic information from the receptors and were able to clone them in pure form. Arch Venture Partners licensed the receptors, and Adolor was in business.
About a decade ago, research showed that in certain circumstances, some opiates could work on the sensory opiate receptors - those outside the brain and spinal cord. When the body experiences an inflammation - a sunburn, for instance - opiate receptors are expressed at that site, Farrar explained. Researchers found that if those peripheral pain receptors were activated, pain relief followed.
One of Adolor's short-term projects is to develop ``anti-hyperalgesics,'' which work on the peripheral opiate receptors. Most pain, Farrar said, is associated with hyperalgesia, pain that would otherwise be innocuous. Take sunburn, for instance. When most people stand in a hot shower, they don't really notice how hot the water is. If they do so with a sunburn, though, they feel pain.
Adolor licensed a compound from the University of California that it calls ADL 2-1294. ``We just finished a trial in burn patients, and it's quite effective,'' Farrar said. The company also hopes to do a study on postsurgical patients.
Company researchers have also found another interesting aspect of peripheral receptors. ``The same fiber that says, `Ow, this hurts,' also sends, `Oooo, this itches,' '' Farrar said. The brain can tell the difference between pain and an itch, he said. ``But if we can block the pain, we can probably also block the itch.''
Tests so far have found the compound effective for itching, Farrar said, and Adolor hopes to have the compound in clinical testing by the end of the year. The goal is to develop ADL 2-1294 into a topical product - eye drops, cream, lotion - all different formulations of the same compound.
Because ADL 2-1294 isn't as effective if taken orally or given intravenously, the company started its own research to find such a compound. It found one and now expects to launch clinical trials of it as early as January.
Adolor also has a third drug in development to try to prevent constipation in cancer and postsurgical patients who use narcotics. Because of its research with opiate receptors, Adolor knew that constipation was a side effect of narcotic use. Last summer, it licensed a compound from Roberts Pharmaceutical Corp., a company that specializes in gastrointestinal drug research.
While it still must undergo scrutiny and requires approval by the Food and Drug Administration, Adolor's first product could hit the market sometime after 2001, said Peter J. Schied, vice president and chief financial officer.