Avanir Pharmaceuticals Inc. completed the rolling submission of its new drug application for Neurodex, a treatment developed for pseudobulbar affect (PBA).
The neurological condition, also known as pathological laughing and crying, emotional lability and emotional incontinence, is characterized by an emotional loss of control, and it has no FDA-approved therapies.
"This is a very important milestone for our company for many reasons," said James Berg, Avanir's vice president of clinical and regulatory affairs, adding that all the firm's 65 employees feel the achievement because "they've all made contributions to it."
Symptoms of PBA include uncontrollable crying or laughing that is out of context with the social setting. It occurs secondary to neurological disease or injuries including amyotrophic lateral sclerosis (Lou Gehrig's disease), multiple sclerosis, stroke, traumatic brain injury and dementias such as Alzheimer's disease.
Berg noted that advancing the program to this point has been satisfying "because this condition is devastating to the people who suffer from it and to the family members or caregivers who labor with these folks who already have a very difficult diagnosis."
The San Diego company's FDA submission, which began six months ago, contains data from two controlled, multicenter Phase III trials: one in amyotrophic lateral sclerosis patients and the other in multiple sclerosis patients. In the amyotrophic lateral sclerosis trial, the Neurodex arm showed statistically and clinically greater improvements than both the dextromethorphan-only arm (p=0.0013) and the quinidine-only arm (p=0.0002) in the primary efficacy endpoint, change in the Center for Neurological Study Lability Scale. Similarly in the multiple sclerosis study, Neurodex patients exhibited a significantly greater reduction in that score than those receiving placebo (p<0.0001).
The NDA also contains data from an ongoing, open-label safety study testing long-term exposure to Neurodex in patients with PBA associated with a variety of neurological disorders. Additional safety data are still to be submitted, including a 120-day update required by FDA regulations.
"We believe the NDA has addressed, in detail, all aspects of chemistry, non-clinical and clinical development," Berg said, adding that the agency is comfortable with the PBA indication. "They never had any questions about what pseudobulbar affect is."
If the agency accepts the filing - generally after a 60-day period - the review process begins. Avanir has requested a priority review, given the drug's first-in-class status, which, if granted, would lead to a regulatory decision by the end of the year. Its estimates point to about 1 million PBA patients that could be treated with the compound.
Neurodex is made of dextromethorphan and an enzyme inhibitor that slows the otherwise rapid metabolism of dextromethorphan, which might work to control PBA by reducing excessive glutamate excitatory neurotransmission. It is thought that neurological diseases and injuries impact the excitatory action of glutamate, which, when excessively signaled, leads to neurological damage.
The company, which earlier this year gained full rights to the compound, has been considering commercialization plans. All options remain open, Berg said, ranging from internal marketing possibilities to potential partnerships. In fact, Avanir is in the process of finding a new corporate head for the company's foray into commercialization.
Its previous president and CEO, Gerald Yakatan, left last month after a long tenure of steering Neurodex. Avanir has been developing it since sublicensing rights in 2000 from IriSys Inc., another San Diego company founded by Yakatan. But Avanir secured remaining rights to the compound though a $1.9 million payment and 2 million share issuance to IriSys. (See BioWorld Today, March 10, 2005.)
Soon after, Avanir raised $17.1 million in a common stock offering that cleared a shelf registration. The financing filled the firm's accounts with enough reserve funding to sustain operations well beyond FDA action on the NDA, which was filed in the common technical document format to support overseas filings. Agreements for marketing abroad are likely. (See BioWorld Today, April 8, 2005.)
In addition to the PBA program, Avanir also has been developing Neurodex for another indication, painful diabetic neuropathy. The company recently began a Phase III trial to further test the compound in that area under a special protocol assessment reached earlier this year with the FDA that calls for a pair of pivotal studies. (See BioWorld Today, Jan. 14, 2005.)
Also in its pipeline is a product for asthma that has completed a Phase I study. A dose-escalating trial is on tap, as well, to further evaluate the compound, which stems from a series of small molecules that selectively inhibit or prevent the production of IgE antibodies. The company also has a commercialized product, Abreva, an over-the-counter cold sore treatment marketed in North America by GlaxoSmithKline plc, of London.
On Thursday, Avanir's shares (AMEX:AVN) lost 1 cent to close at $2.80.