By Patrick Rajan, Team Leader, Pharmaceuticals & Biotechnology Practice

Despite the fact that generic alternatives to Neurontin became available in late 2004, many industry experts have stated that the impact should be minimal due to impending launch of Lyrica.  However, in light of the recent setbacks dealt by the FDA, can the drug still meet the lofty expectations placed upon it as the successor to Neurontin? 

Developed by Pfizer, Lyrica is a 3-substituted analog of gamma-amino butyric acid (GABA).  Both Neurontin and Lyrica share a similar mechanism of action: binding to calcium channels and modulating calcium influx as well as influencing GABAergic neurotransmission.  Lyrica has been generally considered to be a newer and better follow-up to Neurontin since it can achieve efficacy at lower doses.  In 2003, global sales for Neurontin were approximately $2.7 billion.  As generic gabapentin alternatives finally became available in October’2004, it was projected that Lyrica could not only maintain Neurontin’s patient base but also draw revenues from additional indications such as anxiety and diabetic neuropathic pain.  However, even as the FDA finally approved it for sale, Pfizer now faces unexpected challenges that could derail Lyrica’s revenue potential. 

First, federal regulators designated Lyrica as a controlled substance.  As a drug subject to the rules of the Drug Enforcement Administration, statutory requirements for prescribing controlled substances are likely to make it less attractive in the eyes of some patients and physicians.  Neurontin is not classified as a controlled substance, putting generic gabapentin manufacturers in a better selling position versus Lyrica despite fewer indications.  The therapeutic benefit of Lyrica as compared to Neurontin is not dramatic, and this classification will only make Lyrica a harder drug to advertise and prescribe, making doctors more inclined to prescribe generic gabapentin.

Second, the major selling point for the product (expanded labeling) has not developed in the desired fashion Pfizer had intended.  The FDA has reviewed Lyrica for four different indications -- neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia, as an add-on therapy in the treatment of partial epileptic seizures, and for the treatment of generalized anxiety disorder in adults. Lyrica was only cleared for neuropathic pain due to diabetes and postherpetic neuralgia.  The FDA has rejected Lyrica as a treatment for epileptic convulsions and anxiety.  If Pfizer had gotten all the indications it was seeking for Lyrica, the drug could have been positioned not only as a first-line therapy for neuropathic pain and epilepsy but also as a viable substitute for benzodiazepines in the lucrative anxiety market.  Anxiety disorders are considered the most prevalent of psychiatric disorders.  An estimated 19 million adult Americans suffer from anxiety disorders.  Generalized anxiety disorder is one of the prevalent anxiety disorders and affects 4 percent of the U.S. population.

In spite of all these adverse events, Lyrica still will be a key performer for Pfizer.  Off-label usage in neuropathic pain sufferers propelled Neurontin to blockbuster status.  But it does not have an indication for diabetic neuropathic pain, something that should give Lyrica a critical competitive advantage over generic manufacturers since it is considered to be the most lucrative market segment.  DPNP, a key symptom of diabetic neuropathy caused by chronic glycemia, affects approximately 3.8 million patients in the United States.  Although it may not surpass or even meet the peak performance level of Neurontin, Lyrica should be able to weather these setbacks to become the latest in the long line of Pfizer blockbuster drugs.