Unfavorable results from three early Phase II studies prompted Adolor Corp. to return to Phase I for ADL 10-0101, a stimulant of peripherally restricted kappa opioid analgesic used for visceral or inflammatory pain.
Wall Street viewed the news as no more than a minor setback as the company’s stock (NASDAQ:ADLR) closed Monday at $11.02, down 13 cents.
John Farrar, president and CEO of Exton, Pa.-based Adolor, attributed the steady price to at least two issues. The first, he said, is the nature of early proof-of-concept Phase II trials, and the second relates to the fact that ADL 10-0101 is not the company’s lead product. Instead, ADL 8-2698, an oral, non-absorbed small-molecule opioid receptor antagonist in Phase III trials for opioid bowel dysfunction, is the company’s primary focus. Some data from the Phase III are expected this quarter.
“Most of our value is in ADL 8-2698,” Farrar told BioWorld Today. “But the kappa program represents something long term.”
Peter Schied, the company’s chief financial officer, added, “We are plowing through new territory. This is a brand new class of compounds and that’s why we’re going pretty slowly. The Street is saying to us, Get your science done and then we’ll reflect that in the future.’ Our objective is to get the basic science done before we start making a lot of noise about it.”
Indeed, Thomas Dietz, an analyst with Pacific Growth Equities in San Francisco, released supportive research notes. “The results of these completed studies lead us to believe that the lack of a good understanding of the maximum tolerated does for ADL 10-010 has limited Adolor’s ability to appropriately dose patients. Our view of the completed study’s design and results does not give us cause to believe that ADL 10-0101 will be unsuccessful.”
The proposed expanded Phase I trials will help the company better determine the maximum tolerated dose of ADL 10-0101, which is designed to stimulate pain relief receptors on pain- and itch-sensing nerves.
Farrar said the compound ultimately would be tested in Phase II for inflammatory pain and visceral pain. “We’re going to expand our Phase I program, further refine the active dose or the highest safest dose that can be used, which will then take us to further Phase II clinical trials,” he said.
In the Phase II studies disclosed Monday, Adolor said patients were given a single intravenous dose of ADL 10-0101, and none of the patients reported dose-limiting adverse events.
The first trial looked at 14 patients suffering from chronic pancreatitis pain; five took a placebo and the other nine took a single intravenous dose of ADL 10-0101. There was considerable variability in the pain scores of patients in the active and placebo treatment groups, and a reduction in pain scores vs. the placebo group was not observed. The different clinical results between this and the previously completed study in pancreatitis pain may be due to structural differences between the two studies, the company said in a prepared statement.
The second study evaluated three patients undergoing hysteroscopy, in which the primary clinical endpoint was adequacy of pain relief such that patients would not require other pain relievers. The primary clinical endpoint was not achieved, and no adverse CNS effects were reported, the company said.
And the third trial was a double-blind, placebo-controlled study of 20 colonoscopy patients using ADL 10-0101 in 20. The primary endpoint was the number of patients who required the administration of additional analgesics to complete the procedure. The primary endpoint was not achieved, and no adverse CNS effects were reported, the company said.
“If you look at the reality of the small study, for example, the pancreatitis study, that was an extremely tightly controlled study where the patients had training and pain assessment and there are a lot of issues in that,” David Jackson, senior vice president of research and development at Adolor, told BioWorld Today. “It made it a study that was very interesting scientifically, but very tight. Then we went to a bigger study and loosened the requirements and made it much easier to get patients into the study. In the other two, we were kind of seduced along the way with our first studies and we saw activity in that dose.”