BY OUR PHARMA CORRESPONDENT
31 August, 2005: Clinical studies using Renovis Inc’s new drug to treat sciatica failed to show expected results.
Announcing the phase II clinical trial results on REN-1654 in patient-volunteers with sciatica, Renovis said in a release the results indicate that, although therapy showed a positive trend in pain relief, it did not reach statistical significance in its primary endpoint of change in average daily spontaneous pain ratings at the end of a three-week treatment period compared to placebo.
An analysis of secondary endpoints in the study showed a statistically significant reduction in maximum daily leg pain at the end of weeks one and two in subjects treated with REN-1654 compared with placebo, but the reduction in maximum daily leg pain was not statistically significant after three weeks of treatment due to a spontaneous reduction of pain in the placebo group.
The company has decided to discontinue development of REN-1654 as an oral medication and is instead exploring alternate routes of administration based on the modest effectiveness observed at the dose tested in this study, and safety findings that would limit testing of higher oral doses.
REN-1654 is a small molecule inhibitor of the release of TNF-alpha and other proinflammatory cytokines that has shown activity in animal models of neuropathic pain.
The finding that REN-1654 may provide a modest degree of relief of leg pain for sciatica patients is consistent with published data from several small open-label studies using infliximab or etanercept injections in human patients, which suggested that a reduction of TNF-alpha levels could be a potential treatment for sciatica leg pain. While the company will not continue to develop REN-1654 as an oral medication, it will continue to analyze the data from this study to consider whether there may be alternative routes for advancing this compound or mechanism of action, the release stated.
The phase II double-blinded, placebo-controlled, multi-center study enrolled 74 patient-volunteers who had developed leg pain due to lumbosacral radiculopathy of no more than 12 weeks duration prior to enrollment. Following a baseline week of no treatment during which they recorded daily spontaneous leg pain, maximum leg pain, and other factors related to activities of daily living, study subjects were randomized into two double-blind groups and received single daily oral doses of placebo or 100 mg REN-1654 for 21 days. Individuals who received treatment with an epidural or intrathecal agent, corticosteroids, antiretrovirals, other anti-TNF alpha agents, or topical analgesics within two weeks before the start of the trial were not eligible for the study. Study subjects were allowed to continue standard care with other analgesics, anticonvulsants, anxiolytics or muscle relaxants if they had been using such medications for at least four weeks prior to enrollment, received stable doses for at least two weeks prior to the study, and met all other eligibility requirements including continuing to have persistent moderate to severe pain.
Renovis is a biopharmaceutical company developing drugs to treat neurological diseases and disorders. The most advanced product candidate, Cerovive (NXY-059), is in phase III clinical trials for acute ischemic stroke with exclusive licensee, AstraZeneca AB. Cerovive (NXY-059), an investigational drug under development by AstraZeneca and licensed from Renovis, has a proposed mechanism of action of free radical trapping. It is being studied as a neuroprotectant in clinical trials based on effects seen in experimental models of acute ischemic stroke. The company has a worldwide collaboration and license agreement with Pfizer to research, develop and commercialize small molecule VR1 antagonists, and a research and development collaboration with Genentech to discover and develop anti-angiogenesis drugs and drugs that promote nerve re-growth following nervous system injury.
BY OUR PHARMA CORRESPONDENT