Global survey shows neuropathic pain under-diagnosed and under-served

A new seven-country global survey has revealed that effective patient-doctor communication is vital to earlier, accurate diagnosis and treatment for patients with neuropathic pain (NeP) and has concluded that NeP is an underserved market.

NeP is defined as pain caused by injury to, or disease of, the nervous system, or pain derived from damage to the nervous system itself, rather than pain detected by the nervous system due to external stimuli, such as burns or broken limbs. NeP is estimated to impact between 2.8 per cent and 4.7 per cent of the global population, with an increasing incidence with age.

Central NeP occurs as a result of damage to the CNS and can be caused by Multiple Sclerosis (MS), spinal cord injury, stroke or cancer. Peripheral NeP arises from damage to the peripheral nervous system, caused by diabetes, cancer, HIV infection, carpal tunnel syndrome, Post-Herpetic Neuralgia (PHN), amputation (phantom limb pain), back injury, leg ulcers and iatrogenic injury through surgery.

NeP symptoms are described by patients as a burning, shooting, stabbing or electric shock-type sensations. Symptoms are often worse at night and traditional pain treatments, such as anti-inflammatories and paracetamol are ineffective. Other common NeP symptoms are allodynia (response to non-painful stimuli), hyperesthesia (exaggerated pain response to light touch), hyperalgesia (exaggerated pain response to non-painful stimuli), hyperpathy (persistent pain even after cause of pain is removed) and parasthesia/ dysesthesia (abnormal and unpleasant tingling or "pins and needles" sensation.

The survey results were presented by a panel at a media call in London on 1 March 2007. The panel included Dr Troels Jensen, professor of experimental and clinical pain research at the University of Aarhus and consultant neurologist at Aarhus University Hospital; Dr Jordi Serra, a consultant in the department of neurology and neurophysiology in Barcelona; Professor Ralf Baron, head of the Neurological Pain Research and Therapy of Kiel University and senior-vice president of US-based market research firm Harris Interactive, Erich Kramer. Ian Semmons represented the Neuropathic Pain Network and spoke about his own experiences as an NeP patient.

The survey, which was commissioned back in July 2006 and funded by Pfizer, was a multi-region analysis of NeP patients and the doctors who treat them. Approximately 700 diagnosed NeP patients and 700 doctors were surveyed in Finland, Germany, Korea, Italy, Mexico, Spain and the UK between August 2006 to January 2007.

Senior clinical lecturer in palliative medicine and honorary senior research fellow at the University of Leeds and member of the presenting panel commented: "In many countries, doctors have increasingly limited time with patients, posing a particular challenge with NeP, which has historically difficult to identify. For these doctors, screening tools may be one solution, alerting doctors to the possibility of NeP in a timely manner. Whether through the use of these tools, or by simply engaging in thorough conversations, improving communication about symptoms of NeP can help us meet the needs of these long-suffering patients."

The survey's key findings were as follows:

1. Identifying NeP can be a long and difficult process - from symptom onset, patients can wait an average of 5.7 to 19.5 months to see a doctor. The majority of patients said that the delay was due to the fact that they thought the pain would go away by itself.
   
2. The survey found that doctors who understood their patients NeP symptoms were more likely to discuss symptom characteristics, medical history and location of pain in the body.
   
3. Screening tools for NeP were not widely used - in most countries surveyed, doctors, the majority of whom were general practitioners, did not find the identification of NeP easy. Most doctors did not report using a screening tool, such as a pin-prick test, on most of their patients. In many countries doctors were unaware that screening tools were available, but were keen to learn more about them.

Treatment and market
According to a 2005 Research & Markets report, it was estimated that 37.6 million patients across the seven major markets suffered from CNS NeP, while 170.1 million suffered from peripheral NeP. The report cites that the diagnosis and treatment of pain is often a hit or miss affair, due to the subjective nature of the patients' experience of it and doctors' lack of education about the syndrome.

The typical treatment of pain is to prescribe opioids, non-opioids and non-steroidal anti-inflammatory drugs (NSAIDs), as well as adjuvant therapies, such as anti-depressants and anti-convulsants. Misdiagnosis and lack of treatment options have slowed growth in the pain market. The report concludes that increased education for patients, doctors, nurses and pharmacists is an on-going unmet requirement.

NeP is more common in certain populations - up to a quarter of diabetic patients, a third of cancer patients, over half of patients suffering from shingles develop post-herpetic neuralgia (PHN), a third of patients following spinal cord injury and around five per cent of people will suffer NeP after having a stroke. The survey revealed that these figures are likely to be underestimated as NeP is often misdiagnosed.

The report forecast that growth in the NeP market would increase modestly and that the prevalence of the NeP market would increase to 39.1 million individuals, which was complimented by the forecast growth of the peripheral NeP market to 164.8 million individuals by 2011.

The modest predictions of the Research & Markets report is contradicted by a 2005 Datamonitor report, which said that the current USD 1.7 billion NeP market was expected to triple to USD 5.5 billion (EUR 4.2 billion/ GBP 2.9 billion) by 2015.

Main NeP agents

The traditional
The NeP market is being driven by growing demand for Pfizer's Lyrica (pregabalin) and Eli Lilly's antidepressant, Cymbalta (duloxetine), as well as Teikoku Seiyaku's Lidoderm/Versatis (lidocaine) patch for the treatment of Post-Herpetic Neuralgia (PHN) pain.

Lidoderm is licensed to Endo for sale in the US and Versatis is licensed to Gruenenthal for the UK. For Endo in the US, Lidoderm racked up sales of USD 419 million in FY05. For H1 FY06, sales were USD 266 million. However, lidocaine is off-patent and its reformulation into a transdermal patch will only guarantee Endo ethical sales until the extended patent fails in 2010, when generic competitors begin to produce their own versions.

Lyrica sales totalled USD 463 million in H1 FY06, so Pfizer has set a USD 1 billion goal for the year for all indications, claiming it as one of its most successful drug launches ever.

Lilly's SNRI-inhibitor Cymbalta, which is prescribed as an antidepressant, has been approved by the FDA in the US to treat nerve pain associated with diabetes, while the company is conducting late-stage studies to treat other forms of chronic pain. For H1 FY06, Cymbalta sales totalled USD 544 million and USD 680 million for FY05, although the figures do not distinguish between sales for pain treatment and those for depression only.

US biotechnology company, Cephalon, has received FDA approval in the US for its cancer pain drug, Fentora (fentanyl), which is also being tested for the treatment of back pain and other forms of NeP.

The unconventional
A product which is set apart from conventional NeP treatments is US-based Allergan's Botox, a powerful neurotoxin popularised as a cosmetic treatment used to freeze the facial muscles to reduce wrinkles. Botox is also being used to treat dystonia and blocking nerve impulses in NeP patients.

Shares in GW Pharmaceuticals, a UK-based pharmaceutical company, have been rising steadily on the back of a USD 273 million (GBP 140 million) deal with privately owned Japanese pharmaceutical firm, Otsuka, to market its cannabis-based drug Sativex in the US for the treatment of NeP associated with cancer, MS and other CNS diseases.

GW has UK Government permission to use cannabis to make cannabinoid-derived pharmaceuticals and will be paid an initial fee of USD 18 million by Otsuka. The rest will be made available to GW in milestone payments. Both companies will collaborate to develop other cannabis-based drugs for a range of conditions.

Sativex has already been approved for treating neuropathic pain in Canada, while the EU commission is considering whether to approve it for MS spasticity, while the drug is also in US trials for treating cancer pain.

Pfizer the sponsor, Pfizer the player
The fact that Pfizer sponsored the Global Neuropathic pain survey comes as no surprise, especially as it is close to losing patent protection on gabapentin. The drug is approved for the treatment of Post Herpetic Neuralgia (PHN) in the US, but is also used to treat unapproved conditions due to minimal side effects and low-level drug interaction profile.

Pfizer is now busy managing the lifecycle of gabapentin's replacement product, pregabalin and will try to market gabapentin in markets where pregabalin will eventually launch, so doctors will accept the replacement on the back of gabapentin's reputation.

The FDA has not approved gabapentin for the treatment of diabetic neuropathy (DNP), however, so the market remains wide open to competitor products. Competition in the DNP market will be something to watch, especially other CNS players, such as GlaxoSmithKline and Eli Lilly, will soon be reinforcing their presence.

GSK and US-based biopharmaceutical company, Xenoport, for example, are co-developing and co-marketing XP13512, which is currently in phase III development for restless legs syndrome and phase II for neuropathic pain. XP13512 is a pro-drug of gabapentin, improving on the original's bioavailability. Xenoport could rack up USD 290 million (EUR 220.8 million/ GBP 150.3 million) in milestones, based on successful commercialisation for both the indications.

According to a 2006 Datamonitor report, Pfizer is likely to continue to be market leader in the NeP market in the short-term, thanks to the impending introduction of pregabalin. Despite this early advantage, the report goes on to say that the world's largest pharmaceutical firm will see its market share eroded by other emerging treatments with novel modes of action. The main reason for this is that NeP itself is a collection of symptoms and that one drug does not fit all cases. The emerging NeP market is one which further heralds the approach of individualised healthcare, so no one drug will dominate for long.