In the pipeline

The symptoms sound innocuous-uncontrolled laughing and crying-but its effects can be seriously disabling in social and occupational settings. Pseudobulbar affect (PBA), also known as emotional lability, is believed to affect up to one million patients with neurological disorders, including amyotrophic lateral sclerosis (ALS), multiple sclerosis, Alzheimer's disease, and stroke. Currently there are no approved treatments for this condition. Avanir Pharmaceuticals hopes its investigational drug, Neurodex, will fill this void. The company has submitted the final modules of a rolling submission of the NDA for Neurodex, seeking approval to market the agent for PBA.

It is hypothesized that neurological diseases and injuries impact the excitatory action of glutamate, resulting in excessive signaling, and leading to neurological damage. The investigative oral formulation, also known as AVP-923, contains 30 mg each of dextromethorphan and quinidine sulfate. Dextromethorphan, most widely known for its use as a cough suppressant, is also an NMDA-receptor antagonist and a sigma-1 receptor agonist and may work to control PBA by reducing excessive glutamate excitatory neurotransmission. However, giving a sufficient dose of dextromethorphan to penetrate the central nervous system would result in unfavorable side effects such as nausea and vomiting.

Quinidine sulfate, a well-established antiarrhythmic agent, is used at a low dose to inhibit the CYP450 2D6 enzyme responsible for the metabolism of dextromethorphan, thus allowing for the use of lower doses of the substance.

Avanir will submit additional safety data from an ongoing open-label study, including a 120-day safety update required by FDA regulations.

Lupus drug gets fast-track status The current standard of care for patients diagnosed with lupus nephritis often involves treatment with high doses of corticosteroids and immunosuppressives, which can cause severe side effects and may leave patients vulnerable to opportunistic infections. La Jolla Pharmaceutical's investigational product, Riquent (abetimus sodium) was specifically designed to decrease the severity and number of renal flares in patients with systemic lupus erythematosus (SLE) by selectively reducing antibodies to double-stranded DNA (dsDNA) and their parent B cells via antigen-specific tolerance.

Lupus is a chronic, potentially life-threatening, autoimmune disease in which patients' diseased B cells produce antibodies to dsDNA. These antibodies are believed to cause lupus renal disease. Approximately 50% of lupus patients have lupus renal disease, which can lead to irreversible kidney damage, kidney failure, and the need for dialysis and is a leading cause of death in lupus patients.

Analysis of data from two clinical trials demonstrated that treatment with abetimus resulted in durable and persistent reductions in anti-dsDNA antibodies in SLE patients. Health-related quality of life was also significantly improved in the abetimus-treated group. The drug was well tolerated, with the rate of adverse events and mortality similar to placebo.

The FDA has granted La Jolla fast-track status for abetimus for the treatment of lupus renal disease.

NDA filed for next-generation beta-blocker Nebivolol is an investigational long-acting cardioselective beta-blocker with vasodilatory properties triggered by enhancement of endothelial nitric oxide release. It has been purported that this dual mechanism of action offers an improved tolerability profile for nebivolol as compared with other commonly used drugs used to treat hypertension. Mylan Laboratories Inc. under its branded subsidiary, Mylan Bertek Pharmaceuticals, has received an approvable letter from the FDA for the use of nebivolol for the treatment for hypertension.

In a 12-week, double-blind randomized multicenter study comparing nebivolol 5 mg daily with atenolol 100 mg daily, the two drugs induced similar significant antihypertensive effects. Distribution of responders and nonresponders was similar for nebivolol and atenolol, while nebivolol showed a better tolerability profile and a lower incidence of side effects.

Nebivolol is already registered in more than 50 other countries outside of North America.