Shares of Avanir Pharmaceuticals Inc. shot up 309 percent Wednesday after the company announced positive top-line data from a Phase III trial of Zenvia in diabetic neuropathic pain.
Avanir's stock (NASDAQ:AVNR) traded up $3.92, on about 90 times its normal volume to close at $5.19.
But $5.19 is still a long way from the company's 52-week high of $14.69. The shares started a downward slide early last year, then lost nearly half their value in the fall when the FDA delivered an approvable letter rather than the anticipated approval for Zenvia in involuntary emotional expression disorder (IEED). Investors continued to punish the stock early this year as the FDA confirmed it would require a second trial in IEED prior to considering the drug for approval, prompting Avanir to restructure. (See BioWorld Today, Nov. 1, 2006, and March 30, 2007.)
Wednesday's initial efficacy and safety data from the 379-patient Phase III trial in diabetic neuropathic pain offered encouragement to investors.
On the efficacy side, the trial met its primary endpoint of pain reduction according to the Pain Rating Scale as measured through daily diary entries. Patients receiving Zenvia twice daily at 45/30 mg or 30/30 mg demonstrated significantly lower pain ratings than those in the placebo group (p<0.0001).
Secondary endpoint data also looked good. Patients at both doses of Zenvia experienced significantly greater average pain relief reductions than placebo patients as measured on the Pain Relief Rating Scale. The group receiving the higher dose of Zenvia also demonstrated statistically significant improvements in the Pain Intensity Rating Scale compared with placebo.
On the safety side, Avanir reported no deaths and no significant differences in serious adverse events between the Zenvia and placebo groups. The most commonly reported adverse events - dizziness, nausea, diarrhea, fatigue and somnolence - were generally mild to moderate in nature, although 25.2 percent of patients in the higher-dose Zenvia group and 21 percent in the lower-dose group discontinued treatment due to adverse events, compared to only 11.4 percent in the placebo arm.
During a conference call, investors asked if the safety data from the diabetic neuropathic pain trial could be used to assuage the FDA's concerns about Zenvia's safety in IEED. The approvable letter in IEED cited questions about safety, specifically relating to cardiovascular issues and side effects in patients with amyotrophic lateral sclerosis (ALS), as well as questions about secondary efficacy endpoints and statistical analyses.
Avanir spokespersons said during a conference call that they plan to bring up the new data with the FDA, but they are moving forward with the expectation that they will still need to complete the second Phase III trial in IEED as well as a pre-planned second Phase III trial in diabetic neuropathic pain. The company was not available for further comment.
Zenvia is a combination of dextromethorphan and the enzyme inhibitor quinidine, which serves to increase the bioavailability of dextromethorphan. The second Phase III trial in IEED will use a new, lower quinidine dose formulation in an effort to address safety concerns. Avanir said in a news release that it would consider "whether it would be necessary or advisable to study a similar lower dose of quinidine in the second Phase III trial being planned for diabetic neuropathic pain."
Avanir also is working with Eurand International SpA, of Milan, Italy, to develop a controlled-release formulation of Zenvia with the objective of blunting the quinidine exposure.
The second Phase III IEED trial is slated to begin this year and could lead to a new regulatory submission within two years. The second Phase III diabetic neuropathic pain trial will follow discussions with the FDA.
As of Dec. 31, Avanir had cash and investments of $17.6 million available to fund its trials. Last month's restructuring reduced annual operating expenses to $20 million, and the company is evaluating the sale of its preclinical and early clinical stage pipeline programs as well as its marketed schizophrenia drug FazaClo.
Spokespersons from Aliso Viejo, Calif.-based Avanir were not available for questions.