Shares of Renovis jumped more than 90 percent Wednesday on Phase III data showing its neuroprotectant drug Cerovive reduced disability in ischemic stroke patients.
"This is a good day for Renovis," said Corey Goodman, president and CEO of the South San Francisco-based company, which licensed Cerovive to London-based AstraZeneca plc for development and commercialization in exchange for milestone and royalty payments.
Preliminary results of the SAINT (Stroke-Acute Ischemic-NXY Treatment) I trial involving more than 1,700 patients in Europe and other areas showed that the drug met its endpoint vs. placebo, defined as a statistically significant reduction on the primary outcome of disability three months after an ischemic stroke, as measured by the Modified Rankin Scale. The drug also confirmed safety and tolerability results found in Phase I and II trials.
Renovis' stock (NASDAQ:RNVS) doubled in pre-open trading Wednesday and ended the day at $13.17, up $6.38, or 94 precent.
"In the entire history of stroke trials, and after lots of failures over the last 15 years, this is the first time a neuroprotectant drug has, in a difficult Phase III trial, hit its primary endpoint," Goodman said, adding that the results had a "p" value of 0.038. "I believe that's really good news for patients and families."
Goodman said early data also indicated that the intravenously administered Cerovive appeared to be efficacious as both monotherapy and in combination with tPA, a thrombolytic agent for ischemic stroke. Results also were observed across the entire range of patients, rather than limited to subgroups.
The drug missed showing statistical significance in a co-primary endpoint - or as Goodman described it, a "glorified secondary" endpoint - that measured a change in neurological impairment based on the National Institutes of Health Stroke Scale. But that miss might not affect regulatory approval.
"We believe that [the Modifed Rankin Scale] is what the regulatory authorities and physicians are looking for," Goodman told BioWorld Today. The NIH scale's neurological measurement is "much more complex, but we believe the focus is on a decrease in disability, so patients can get out of bed, control bodily functions and motor skills."
AstraZeneca is conducting a second Phase III trial, SAINT 2, which is on schedule, in North American ischemic stroke patients. A Phase IIb study called CHANT (Cerebral Hemorrhagic and NXY-059 Treatment) also is ongoing to evaluate Cerovive in patients with hemorrhagic stroke, with an emphasis on safety data.
"What we would ultimately like to show is that the drug is safe for all stroke patients," Goodman said, so it can be administered prior to a CAT scan and be used "in the emergency room or even the ambulance."
The CHANT trial will enroll a total of 600 patients. An independent Data Safety Monitoring Board recently conducted an interim analysis of 200 patients, and recommended that the trial proceed, Goodman said.
"Clearly, we need to wait and see if we get the same results in SAINT 2," he said, adding that AstraZeneca anticipates results of that trial during the first half of 2006, with the regulatory filing submitted in the second half.
AstraZeneca has exclusive, worldwide rights to Cerovive. Renovis stands to receive milestone payments coinciding with regulatory filings and a "mid-teen" percentage of royalties from a market opportunity potentially worth several billion, Goodman said. There are about 2.2 million strokes reported every year, with only a small percentage - maybe 3 or 4 percent - of those receiving tPA therapy. "We hope to be able to treat the other 96 percent," he said.
The success of the SAINT I trial also adds a boost to other products in Renovis' pipeline, especially a preclinical program to develop an oral neuroprotectant similar to Cerovive. Goodman said the goal would be to provide an orally available drug for patients who have a high risk of stroke or existing ischemic conditions to take as a prophylactic.
Renovis has two products in clinical development. REN-1654, a TNF-alpha release inhibitor, recently failed to show efficacy compared to placebo in a proof-of-concept study in post-herpetic neuralgia, but the company has remained optimistic about an ongoing Phase II study evaluating the product in sciatica. Results of that study should be available during the third quarter. (See BioWorld Today, March 9, 2005.)
REN-850 is in a Phase I program in multiple sclerosis and other autoimmune diseases. Though the company reported success in preclinical studies, Renovis will be evaluating the drug's safety closely since its mechanism of action, the inhibition of leukocyte trafficking, is similar to the multiple sclerosis drug Tysabri, which was pulled off the market by Cambridge, Mass.-based Biogen Idec Inc. and Dublin, Ireland-based Elan Corp. plc, due to the discovery of deaths linked to progressive multifocal leukoencephalopathy. (See BioWorld Today, March 1, 2005.)
"So we'll be looking carefully at that safety data before moving forward," Goodman said.
Renovis has other preclinical products in its pipeline for pain and neuroinflammatory diseases, and also is collaborating with South San Francisco-based Genentech Inc. to discover and develop anti-angiogenic products and drugs for neurological disorders.