Although Renovis Inc.'s neuropathic pain product failed to show statistical significance in post-herpetic neuralgia, the company still has high hopes for REN-1654 in other indications.
Enrollment is continuing in a second Phase II trial of REN-1654, an orally administered TNF-alpha release inhibitor, in patients with sciatica, with results expected during the third quarter. In that trial, investigators are expected to determine through objective measurements whether patients' conditions improve after taking the drug, which was difficult to determine during the Phase II study in post-herpetic neuralgia (PHN).
The PHN trial, which studied an early-onset neuralgia patient population, reported no statistically significant change in the primary efficacy endpoint between the treatment groups and the placebo group, said Randall Moreadith, chief medical officer for Renovis.
"The reason for that turned out to be a very high rate of spontaneous pain remission in the entire population," including the placebo group, he told BioWorld Today. "That was a bit of a surprise to us. The placebo effect rate in the study essentially washed out any potential treatment effect that REN-1654 might have had."
The news didn't concern Wall Street. Following the announcement Monday afternoon, shares of Renovis (NASDAQ:RNVS) rose 21 cents Tuesday to close at $9.07.
The PHN trial enrolled 94 patients with a history of herpes zoster (shingles) followed by persistent pain that lasted from two to 18 months following the onset of the rash. Following a baseline week of no treatment, patients were divided into three groups, with one group receiving 30 mg of REN-1654, one group receiving 100 mg and a third group receiving placebo. Patients recorded their pain ratings on an 11-point scale - 0 being no pain and 10 being the most severe pain - during the course of three weeks, and those figures were provided to researchers. Neither the patients nor the investigators knew whether they were in the treatment or placebo groups, Moreadith said.
About 30 percent of patients in the placebo group achieved a pain reduction of 1 point or greater, compared with 33 percent of patients who received a 30-mg dose of REN-1654 and 37 percent who received a 100-mg dose. The average weekly pain scores were changed by 0.93, 0.60 and 0.57, respectively.
"The patients also recorded secondary efficacy endpoints, such as sleep interference, general activity and allodynia," Moreadith said. Allodynia is characterized by an area of skin painful to the touch.
REN-1654 was found to be safe and well tolerated.
Whether Renovis will return to investigating the drug as a treatment for post-herpetic neuralgia likely will depend on the outcome of the ongoing sciatica trial.
"We'll be advancing it, but only if we see there's going to be a treatment effect," he said. "We'll wait until we see the results of the sciatica study, and then make a decision about whether we would advance REN-1654 in another neuropathic pain condition."
REN-1654 is designed to work by inhibiting TNF-alpha-mediated pain pathways. Moreadith said in vitro studies indicated that the product inhibited both TNF-alpha pathways and proinflammatory cytokines, and researchers hypothesized that, with post-herpetic neuralgia, the onset of pain "might be related to the release of proinflammatory cytokines in either the central nervous system or in peripheral nerves."
That hypothesis became even more attractive as Renovis began preparing for the trial of REN-1654 in sciatica, which is characterized by pain in the back and legs, caused by inflammation or associated herniated disk. TNF-alpha-mediated pathways play a role in sciatica, but the mechanism of neuropathic pain is more clearly related than with post-herpetic neuralgia, Moreadith said, adding, "We have a pretty good chance of seeing a treatment effect in patients in the sciatica trial."
About two-thirds of the 72 patients with sciatica due to lumbosacral radiculopathy have been enrolled in the trial. Renovis said it plans to finish the study in April and post results sometime during the third quarter.
The South San Francisco-based company has chosen not to seek potential partners for REN-1654 now, as it awaits Phase III trial results of its lead product candidate, Cerovive, an intravenous drug for acute ischemic stroke Renovis is developing with AstraZeneca plc, of London.
"Much depends on whether Cerovive will be successful and provide enough revenue for us to develop all our pipeline drugs through Phase II or Phase III," Moreadith said. Cerovive is in two large-scale trials, with more than 1,500 patients each. The SAINT-1 (Stroke Acute Ischemic-NXY Treatment) trial in Europe, Australia, South Africa and Asia has completed enrollment, with results expected next quarter. The SAINT-II trial is ongoing in the U.S., Canada and South America.
Moreadith said Renovis also is developing other neuroprotectants that are related to Cerovive but can be administered orally rather than requiring transfusion, and be designed to provide protection for ischemic brain, heart and kidney tissues. The company is advancing several compounds into preclinical testing.
Last month, Renovis initiated a Phase I trial of its oral, inflammatory drug, REN-850, in patients with multiple sclerosis.