Avanir Pharmaceuticals Inc. received the FDA's blessing to begin a Phase III trial of Neurodex in pain, at the same time continuing work on its rolling new drug application in pseudobulbar affect.
The parties reached agreement on pivotal testing of the drug for painful diabetic neuropathy, a type of chronic neuropathic pain, through a special protocol assessment plan. San Diego-based Avanir said it would begin the Phase III trial in the first half of this year.
"This gives the investment community a little more belief in what you're telling them, because [they see that] the FDA has signed on," Avanir President and CEO Gerald Yakatan told BioWorld Today. "And it's nice for us, too, to know that if we carry out this trial this way and get this result, then that's a study that's eligible for approval."
He added that the interaction with the FDA inherent in the SPA process also helped the company design a trial and analysis plan that could avoid pitfalls that surfaced in studies of other drugs for neuropathic pain. But Yakatan declined to provide specific details of Avanir's upcoming trial.
"We consider it proprietary information," Yakatan said of the trial design procedure, which included the FDA and a third party to consider factors associated with statistics, patients and difficulties in conducting pain studies. "From a competitive standpoint, we think it's useful information that we have, and I don't want to share too much of it. But eventually, we will talk about some things."
Nevertheless, he did concede that it would compare Neurodex to placebo, last at least three months and cost the company about $8 million.
Phase II results, reported two months ago at the meeting of the American Society of Regional Anesthesia and Pain Medicine, demonstrated that Neurodex was well tolerated up to the highest target dose, and patients reported decreased pain intensity that was significantly different from baseline (p<0.0001). The degree of pain relief increased with duration in the four-week, open-label study.
Neurodex is made of dextromethorphan and an enzyme inhibitor that slows the metabolism of dextromethorphan in the liver, a process designed to maintain therapeutic levels for a longer period of time. Neurodex has an anti-excitatory effect by reducing glutamate through the combined actions of sigma-1 agonist activity and NMDA receptor antagonism, suggesting use in treating certain central nervous system disorders such as neuropathic pain.
"Mechanistically, there are a lot of things that the active agent in Neurodex, dextromethorphan, could do," Yakatan said. "We're a small company that had to make decisions on where to spend our development dollars and why."
News of Neurodex's pivotal development for diabetic neuropathy comes just a month after the company began filing a rolling new drug application for Neurodex to treat pseudobulbar affect, a syndrome that occurs with a number of neurodegenerative diseases and is characterized by involuntary laughing or crying. Yakatan noted that Avanir decided to advance that program more quickly because there are no approved products for pseudobulbar affect. Also, the company had more early data in that space.
The FDA has indicated that the product would qualify for a priority review when the company completes its submission, which Avanir expects to do in the first half of this year, meaning a regulatory decision should come before the end of 2005. Avanir has yet to reveal what portions of the application have been submitted, but Yakatan said the FDA suggested a rolling submission to move already compiled results into the review process.
When finished, the filing largely will be based on efficacy data from a pair of completed Phase III trials, as well as safety findings from an open-label study of 300 patients who suffer from brain injuries, spinal damage, and Alzheimer's and Parkinson's disease.
Results from the first Phase III study, which included 140 amyotrophic lateral sclerosis patients, showed that Neurodex effectively palliates pseudobulbar affect and is more useful than either of its components. Further, treatment improved quality of life and relationships for the patients. The second Phase III trial demonstrated its effectiveness in patients with multiple sclerosis who suffer from pseudobulbar affect. (See BioWorld Today, Nov. 20, 2002, and Aug. 25, 2004.)
Avanir has an exclusive license to the compound from a privately held company called Irisys Inc., which Yakatan founded in San Diego. He said the in-licensing deal was completely back-loaded, as Avanir has yet to make a milestone payment on Neurodex.
All development has been focused on the U.S. market, with Avanir's commercial plans still in the works. Yakatan said that before the end of this quarter, the company would disclose its marketing or partnering plans.
"It's really going to be a financial decision," he added, noting that Avanir's 61-employee staff includes personnel with background capable of launching a product should the company choose such a route. Outside the U.S., he said Avanir would out-license its rights and let a partner handle further duties in foreign territories.
Separate from Neurodex, the company's pipeline includes an asthma product in Phase I, as well as small-molecule programs for atherosclerosis and anti-inflammation. Avanir, which expects to advance the latter programs into the clinic later this year and has them in partnering discussions, also is developing monoclonal antibodies for infectious diseases such as anthrax, Staphylococcus aureus and strep throat. On the commercial front, the cold sore product Abreva is marketed in North America by GlaxoSmithKline plc, of London.
"We've been very focused," Yakatan said, "and very efficient."
On Thursday, Avanir's shares (AMEX:AVN) lost 4 cents to close at $3.27.