Mumbai: With just five approved drugs on the market and millions of patients worldwide, neuropathic pain is one of the most attractive indications in the pharmaceutical industry.

Estimated to be worth over $1.68 billion in 2005, the neuropathic pain market is forecast to grow to $5.5 billion by 2015, driven in the US by strong uptake of Pfizer's Lyrica (pregabalin), Eli Lilly's Cymbalta (duloxetine), and Endo's Lidoderm (lidocaine 5 per cent patch), according to a new report by independent market analyst Datamonitor. Indeed, the pipeline for new treatments is one of the most active in the central nervous system (CNS) arena, with more than 90 compounds in development.

One of the most sought-after indications in the pharmaceutical sector

On 18 September 2006, Pfizer received approval from the European Agency for the 'evaluation of medicinal products' (EMEA) to add central neuropathic pain to the label of its new neuropathic pain and epilepsy drug, Lyrica (pregabalin), marking yet another key milestone for one of the industry's fastest growing brands.

For almost a decade Pfizer has dominated the market with its anti-epileptic drug and Lyrica's predecessor, Neurontin (gabapentin), which has been used extensively off-label for a variety of neuropathic pain syndromes, such as painful diabetic neuropathy.

Almost entirely as a result of the success of Neurontin, which at its peak generated $1.32 billion in disease-specific sales across the seven major markets (UK, US, France, Germany, Italy, Japan and Spain), the neuropathic pain market has become one of the most sought-after indications in the pharmaceutical sector. Coupling several million patients with a strong demand for approved therapies, the growth prospects for a new drug in this market are very attractive.

Neuropathic pain occurs when the nerves malfunction and send pain signals in spite of there being no bodily damage to trigger them. Neuropathic pain frequently presents itself in the limbs of advanced diabetes and HIV sufferers (peripheral neuropathic pain), lower back pain sufferers, and is a characteristic of shingles- also known as post herpetic neuralgia, says Datamonitor CNS senior analyst Ben Greener. "Neuropathic pain itself can be felt as a burning or stabbing sensation and can be triggered by non-noxious stimuli (allodynia)."

The neuropathic pain company

With Neurontin, Pfizer fashioned itself as the "neuropathic pain company", with established relationships with prescribing physicians and patients alike. The pharmaceutical giant has also enjoyed relatively little competition from other drug companies over the past ten years. However, the success of Neurontin did not come immediately, Greener says.

He adds, "For the first three years after launch in 1993 as an adjunctive therapy for epilepsy, sales growth was modest as many neurologists regarded the drug as a relatively 'weak anticonvulsant' that was also quite expensive. It was not until the mid-1990s that studies demonstrated an application for neuropathic pain, which, at the time, was a relatively untapped patient group."

The presentation of controlled trial data in journals and at medical conferences, in addition to the questioned promotional practices of Parke-Davis's sales representatives (for which Pfizer, which had since acquired Parke-Davis, had to pay a huge fine of $430 million in June 2004), signified the impressive rise in off-label Neurontin prescriptions for the neuropathic pain from 1997 onwards. In order to appease the FDA, Pfizer sought approval for post herpetic neuralgia in 2002.

Glory days of Neurontin over but Pfizer battles on

In October 2004, Alpharma and Teva launched generic gabapentin capsules despite the fact that Pfizer's motion for a preliminary injunction was still pending. In response, Greenstone Limited, a wholly owned subsidiary of Pfizer, also launched a generic version of Neurontin. This strategy, which is becoming increasingly popular among the big pharmaceutical firms, is helping to recapture some of the gabapentin market share and lessen the impact of rival generic incursion, which has been more severe in the US compared to the EU.

However, the delay in getting Lyrica onto the market was a major setback for Pfizer, Greener says. "There was a 13-month gap between the launch of generic gabapentin in the US and the launch of Lyrica and this saw a huge drop in revenues - global sales of Neurontin fell by 82 per cent to $236m in 2005 and continued to fall in 2006. Pfizer had originally intended to switch physicians straight from Neurontin onto its follow-on product before generic incursion took place."

Lyrica will be a blockbuster by 2007

In a sensible move to recapture share from generic gabapentin, Pfizer launched Lyrica at a competitive price point. Indeed, because of the less frequent daily dosing, long-term treatment with Lyrica may actually be cheaper than with generic gabapentin in the US. For companies looking to launch a reformulation of an older drug, this strategy is even more important amid the ever-increasing cost sensitivities in the pharmaceutical industry, Greener says. "As shown with Lyrica, such tactics have become commonplace in campaigns requiring rapid patient switching, particularly in instances where reformulations are poorly differentiated from their predecessors."

Despite the impact of generic gabapentin, Pfizer is doing a great job of playing catch-up in the market and the uptake of Lyrica has been strong to say the least, Greener says. "Total brand sales are expected to pip the billion dollar mark in 2007, just two years after launch, making it one of the most successful product launches in history."

Unlike with Neurontin, Pfizer has been able to promote the use of Lyrica for neuropathic pain as soon as it launched. Given that neuropathic pain contributes the majority share of sales, it is unsurprising that the marketing emphasis is more on this indication than for its epilepsy labelling. This is exemplified by the Lyrica homepage, where the majority of text is dedicated to information relating to diabetic neuropathic pain and post herpetic neuralgia.

When assessing the potential of Lyrica in the market, the huge marketing resource of Pfizer cannot be underestimated: Pfizer has the strongest and largest CNS portfolio in the industry, worth over $6.3 bn in 2005, which, despite some key patent expiries, is set to grow over the next 10 years, driven by success in the neuropathic pain and insomnia markets.

Secondly: as mentioned before, Pfizer has also attained status as the "neuropathic pain company", which to some extent confers brand loyalty among prescribers. Pfizer continues to show commitment to the disorder by developing a new intravenous drug, traxoprodil (currently in Phase II trials), which will fit the need for a non-oral medicine for severe neuropathic pain in the hospital setting and will complement Lyrica in the market.

No longer a one horse race: Pfizer's legacy benefits other players

The legacy of Pfizer in neuropathic pain is to have laid the groundwork for other companies looking to enter the market. Companies are now more confident to make neuropathic pain the primary indication for their drug candidates and this is reflected in the busy R&D pipeline in 2006, Greener says. "Additionally, the work Pfizer has done with regulatory bodies and clinical trial design has provided a clear route as to how to gain approval for neuropathic pain drugs. Moreover, through the marketing of its products and supporting clinical education seminars, Pfizer has helped to improve physician education and, to some extent, public awareness."