Positive Phase II data of Progenics Pharmaceuticals Inc.'s lead product methylnaltrexone for post-operative bowel dysfunction sent the company's stock skyward on Thursday.
The product demonstrated its ability to accelerate gastrointestinal recovery by at least one day on average compared to placebo. Progenics' stock (NASDAQ:PGNX) rose 13 percent, or $1.98, to close at $17.16.
"We're very encouraged by these results, even in a small patient population," said Richard Krawiec, vice president of investor relations and corporate communications at Tarrytown, N.Y.-based Progenics.
The double-blind, randomized, placebo-controlled Phase II trial included 65 patients evaluated at eight surgical centers. Following a surgery in which a portion of the colon was removed, due to cancer or diverticular disease, the patients received 0.3 mg/kg of methylnaltrexone (MNTX) or placebo intravenously at six-hour intervals for a maximum of seven days.
By receiving treatment with MNTX as opposed to placebo, patients accelerated their time to tolerance of the first full-liquid meal following surgery by 30 hours; the time to tolerance of the first solid meal by 25 hours; the time to first bowel movement by 23 hours; the time to tolerance of the first solid meal and first bowel movement by 27 hours; the time to discharge eligibility by 30 hours; and the time to actual discharge by 25 hours.
"Across the board and on average what you're seeing is an improvement of about one day in a number of medically meaningful endpoints for GI recovery," Krawiec told BioWorld Today.
The analysis of gastrointestinal recovery times was performed using Kaplan-Meier time-to-event methods. Researchers saw significant improvements in time to first bowel movement (p=0.01) and discharge eligibility from the hospital (p=0.03). MNTX was generally well tolerated with no serious drug-related adverse events reported. The most common adverse events were fever and nausea, which occurred in both the treatment and placebo groups.
"We're now in the position where we can conduct some additional, more in-depth analysis," Krawiec said, "and then talk to the FDA to see what the next steps are."
A next step could be moving into Phase III studies with intravenous MNTX. The product already is the subject of two Phase III trials in which MNTX is delivered subcutaneously to treat opioid-induced constipation found in patients with advanced medical illness (AMI). Phase III results from the first trial are expected this quarter, and the second Phase III trial will complete enrollment in mid-2005. If results are positive, the company could submit a new drug application for the AMI indication by the end of 2005.
Intravenous MNTX for post-operative bowel dysfunction is next in line for a regulatory filing, and it would be followed by an oral form of MNTX that completed Phase I studies for the relief of opioid-induced constipation in patients with chronic pain. Progenics expects to soon bring the oral form into Phase II development.
If MNTX reaches all three markets, Krawiec said about 9 million patients could benefit. About 4 million patients are at risk each year for post-operative bowel dysfunction following surgeries, and about 1.2 million patients die in the U.S. each year from AMI.
"For the oral indication, there are about 4 million people who are taking opioids, narcotics, legally every day for chronic pain," Krawiec said, "and one of the serious consequences of taking opioids is constipation."
While MNTX aims to address the constipation and bowel dysfunction problems, it does not inhibit the ability of opioids to control pain. In the Phase II trial, the administration of MNTX did not result in any differences in pain scores compared to placebo.
"This drug is designed to relieve the peripheral effects, the GI effects, that opioids have, and it doesn't penetrate the blood-brain barrier," Krawiec said. "This does not interfere with pain relief."
Post-operative bowel dysfunction results when the body releases endorphins during surgery that bind to opioid receptors in the gastrointestinal tract. The condition is worsened by opioid pain medications given to patients during and after surgery. MNTX is designed to block opioid receptors within the gastrointestinal tract.
There are no approved therapies for post-operative bowel dysfunction, which often results in prolonged hospital stays and increased costs.
"If there are 4 million patients at high-risk for post-operative bowel dysfunction, and you can get them out a day sooner," Krawiec said, "you're looking at a significant number in terms of saving money for hospitalization costs."
Aside from MNTX, Progenics is developing PRO 542, a genetically engineered molecule, designed to selectively target and neutralize HIV, which is in Phase II development; and PRO 140, a humanized monoclonal antibody targeting the HIV coreceptor CCR5, which is in Phase I studies. In addition, the company is developing a recombinant prostate-specific membrane antigen vaccine in Phase I, and its cancer vaccine GMK in Phase III trials for malignant melanoma.
As of Sept. 30, Progenics had about $40 million in cash and more than $40 million in committed government grants and contracts, Krawiec said.