After achieving statistically significant efficacy endpoints in a second Phase III study, Avanir Pharmaceuticals Inc. said it anticipates seeking regulatory approval later this year for Neurodex in the treatment of pseudobulbar affect, a syndrome that occurs with a number of neurodegenerative diseases.
Avanir's stock (AMEX:AVN) Tuesday increased 34 cents, or 17.9 percent, to close at $2.24.
The second pivotal Phase III trial evaluated patients with multiple sclerosis who suffer from pseudobulbar affect (PBA), which is characterized by involuntary laughing or crying. An earlier Phase III study in 140 amyotrophic lateral sclerosis (ALS) patients also ended with statistically significant data. (See BioWorld Today, Nov. 20, 2002.)
Gerald Yakatan, president and CEO of San Diego-based Avanir, told BioWorld Today he would expect FDA action on the Neurodex application 10 months to 12 months after filing, unless the firm receives priority review.
Avanir wants broad approval across neurodegenerative afflictions such as ALS, MS, Alzheimer's disease, Parkinson's disease, stroke and traumatic brain injury, because a certain portion of all patients suffering from those diseases are affected by PBA, Yakatan said.
"These patients will cry when they are not sad and laugh when they are not happy, and it is not something they can control," Yakatan said. "It is devastating to their family life and their interactions at work and with friends."
Neurodex is an oral combination of dextromethorphan (DM) - long known to lessen the cough reflex (it's an active ingredient in Robitussin DM) and apparently effective against PBA - with the enzyme inhibitor quinidine sulfate, which sustains elevated levels of DM in the body.
In the double-blind MS study, 150 patients at 22 clinical sites were randomized to receive either placebo or Neurodex on a 12-hour dosing schedule for 90 days.
The Center for Neurologic Study Lability Scale (CNS-LS), an instrument that assesses frequency and severity of PBA episodes, was used as the primary efficacy endpoint. Patients were required to have a minimum CNS-LS score to participate, the company said.
For the primary endpoint, Neurodex patients had a statistically significant greater reduction in CNS-LS score than those receiving placebo (p<0.0001). The four secondary endpoints evaluated in the trial also were statistically significant in favor of Neurodex: number of PBA episodes (p=0.0003), quality of life (p<0.0001), quality of relationships (p<0.0001) and pain reduction (p=0.026).
Neurodex was well tolerated in that population. The majority of reported side effects were mild or moderate. Of those reported in 5 percent or more of the patients, a statistically significant difference between Neurodex and placebo was observed only for dizziness, the company said.
Data from the MS and ALS trials will be combined with results from an ongoing open-label safety study of 300 patients to make up the pending drug application. Patients in the open-label trial suffer from a range of problems, including brain and spinal damage, as well as Alzheimer's and Parkinson's disease.
Meanwhile, the ALS Phase III trial, completed in June 2002, was a double-blind, placebo-controlled, multicenter trial with three arms that compared Neurodex to each of its two components, dextromethorphan and quinidine.
Avanir holds an exclusive worldwide license to develop, manufacture and market Neurodex for all indications including PBA and neuropathic pain, as well as for the weaning of drug-dependent patients from narcotics and anti-depressants, and chronic cough.
In the first half of next year the company expects to initiate a Phase III trial for Neurodex in neuropathic pain in diabetics, Yakatan said.
The company hasn't determined whether it will partner Neurodex, Yakatan said. "We'll make those decisions over the next six to nine months as we better understand the value of the product, and what would be the best return to our shareholders."