Pain Therapeutics Inc. is terminating development of its irritable bowel syndrome candidate, PTI-901, after Phase III results showed it missed its primary endpoint.

PTI-901 was the subject of a randomized, double-blinded, multicenter U.S. study that compared a daily dose of the drug against placebo in 600 women with irritable bowel syndrome (IBS) over a three-month treatment period. The drug showed a favorable safety profile, as well as statistically meaningful relief in the second month of treatment (p<0.02), but it failed to show the same benefit in the third month of treatment, which was the primary endpoint.

"You've got to feel for these patients," said Remi Barbier, Pain Therapeutics' president and CEO, in a conference call Monday. "When you read the case report form, these patients are hurting. We had hoped to help some of these in at least some way - and we did, briefly, but not sufficiently per FDA standards."

Current regulatory standards require that chronic IBS drugs demonstrate efficacy at the end of three months.

South San Francisco-based Pain Therapeutics said the study was well designed to show durable benefits of PTI-901. Therefore, the clinical results have prompted the company to discontinue all further clinical development of the compound, allowing it to focus on other late-stage products in its pipeline.

"There's something there," Barbier said. "The drug had some beneficial effect, but we think it would take three or four, perhaps as many as five, studies to really figure it out thoroughly."

With each study taking between one and two years to complete and costing between $5 million and $7 million, it didn't fit with Pain Therapeutics' business strategy. "We tried it; it didn't work; we're moving on," Barbier said.

Moving on means the company now will concentrate on its two Phase III candidates, Remoxy and Oxytrex, which are designed to treat severe chronic pain, such as low-back pain, or pain due to osteoarthritis, respectively. The company also expects to file investigational new drug applications for one or more new abuse-resistant opioid painkillers in 2006.

It does not expect "to spend the time and effort" needed to out-license PTI-901, despite its potential in treating IBS, Barbier said.

"IBS is a very, very difficult condition," he continued. "More importantly, there are no preclinical models. It is very difficult to dose these patients correctly. It is a disease that comes and goes just like the tide. It is a disease that is diagnosed by exclusion. It is often confused by primary docs. Even specialists often get it wrong."

Instead, the company will turn its attention to completing talks with the FDA, in order to get Phase III trials of Remoxy and Oxytrex under way. Pain Therapeutics has budgeted for two Phase III studies of Oxytrex in 2006, both of which are designed to address high dropout rates seen in a previous Phase III.

The company's shares lost 20 percent of their value in late November when the number of patients who completed the osteoarthritis study with Oxytrex was lower than expected, and the drug failed to reach statistical significance in reducing opioid-related physical dependency, the primary endpoint. (See BioWorld Today, Nov. 23, 2005.)

Pain Therapeutics expects to start a Phase III trial of Remoxy in the first quarter. That trial, as well as the development of any other opioid-resistant painkillers, will be paid fully by Pain Therapeutics' partner King Pharmaceuticals Inc., of Bristol, Tenn. Last month, the companies signed a potential $400 million partnership, which is expected to close by the end of this year. (See BioWorld Today, Nov. 11, 2005.)

The deal did not include Oxytrex or PTI-901.

Pain Therapeutics will have more than $200 million in cash (about $5 per share) at the end of this year and expects a net cash burn rate of less than $15 million in 2006, so Barbier does not anticipate the company will need to do any fund raising in the immediate future.

Although the company had three Phase III drugs at the end of 2004 and now has only two, Pain Therapeutics is in a good position with its cash balance and partnership with King, Barbier said.

"Fundamentally, I believe we are much better off today as a company than we were one year ago," he said.

The company's stock (NASDAQ:PTIE) dropped 64 cents Monday to close at $6.68.