Pain Programs: Neuropathic Pain
About Neuropathic Pain
According to the International Association for the Study of Pain, neuropathic pain is "initiated or caused by a primary lesion or dysfunction in the nervous system."1 Arcion's drug development programs are currently focused on neuropathic pain that results from disorders of the peripheral nervous system; however, neuropathic pain may also arise from disorders of the central nervous system (brain and spinal cord).
Peripheral neuropathy describes damage to the peripheral nervous system, the communications network that transmits information between the body and the brain. Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Like static on a telephone line, peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body2. Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged. Some patients may experience temporary numbness, tingling, and pricking sensations (paresthesia), sensitivity to touch, or muscle weakness. Others may suffer more extreme symptoms, including burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction.
Two of the more common causes of neuropathic pain are diabetes and herpes zoster that can respectively lead to painful diabetic neuropathy (PDN) post herpetic neuralgia (PHN). According to estimates by the Centers for Disease Control and Prevention, over 17.9 million people in the United States are diagnosed with diabetes3. Given a conservative estimate that 15% of people with diabetes have symptomatic neuropathies, approximately 2.7 million Americans have diabetes-associated neuropathies4. Patients with PDN often experience debilitating pain symptoms that affect day-to-day functioning and quality of life. Herpes zoster (HZ) (shingles) affects an estimated 800,000 persons each year in the United States (US), most of whom are elderly or immunosuppressed5. About 20% of these cases go on to develop enduring pain or PHN6. The prevalence and duration of PDN and PHN increases with age, and in a studies of patients over 65 years of age, greater than 60% of patients reported having moderate to severe pain7. There is a high level of patient dissatisfaction, upwards of 60%, with existing therapies for PDN and PHN8.
Market Opportunity
There is a significant opportunity to develop novel topical formulations of therapeutics for neuropathic pain that can be applied directly to the site of origin of the pain, while leading to fewer systemic side-effects. Currently, there are no treatments that can reverse neuropathic nerve injury. Treatments are palliative, targeted to provide relief of painful symptoms with the goal of reducing pain to tolerable levels. While a number of existing drug treatments are used to provide relief of neuropathic pain symptoms, many of these agents do not provide satisfactory relief in all patients, and their use is often limited by poor tolerability due to systemic side effects.
According to DataMonitor the market for drugs to treat neuropathic pain is currently worth approximately $2.3 billion globally and is expanding rapidly. to more than double to exceed $7 billion by the year 2016.9
Painful Diabetic Neuropathy (PDN)
Diabetic neuropathy is one of the most common complications of diabetes mellitus that is associated with a number of painful conditions. Approximately 15% of diabetics experience mild to severe forms of PDN4 PDN is thought to result from chronic hyperglycemia, which can lead to diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum), particularly the sensory, motor and autonomic nerve fibers. Patients with PDN often experience debilitating pain symptoms that affect day-to-day functioning and quality of life. Arcion's lead clinical program, ARC-4558, is a 0.1% gel formulation of clonidine hycrochloride for topical administration. ARC-4558 is currently in a Phase 2b clinical trial for the treatment of painful diabetic neuropathy (PDN).
Post-herpetic Neuralgia (PHN)
Post-herpetic neuralgia is a serious complication of herpes zoster, or shingles, which occurs in approximately 20% of patients5 secondary to reactivation of herpes zoster (HZ) virus residing in nerve endings within the skin (dorsal root ganglia) following primary infection (chicken pox), often in childhood. The most common symptoms experienced during a shingles outbreak include pain and skin rash. HZ can damage nerve fibers, resulting in pain that can be sharp, piercing, throbbing or stabbing and may result in intolerable skin sensitivity to even the lightest touch3. The pain typically emerges following the healing of the rash and can persist or recur for several months or even years. PHN is more prevalent in the elderly population3.
Arcion has a candidate for the topical treatment of PHN in the early phases of development.
- 1Bogduk, Nikolai; Merskey, Harold (1994). Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms, 2nd edition, Seattle: IASP Press, 212
- 2"Peripheral Neuropathy Fact Sheet," NINDS. NIH Publication No. 04-4853
- 3National Center for Health Statistics, “Health, United States 2008” Table 54
- 4Dyck, et. al. (2993)l. Neurology 43:817-824.
- 5Weaver, BA, (2007). JAOA 107(suppl1):S2-S7
- 6Helgason, et. al. (1996), Eur. J. Clin Prac 2:12-16
- 7Tesfaye, et. al., (1996), Diabeologia 39:1377-1384; Tolle, et. al. (2006), J. Diabetes and Its Complications 20:26-33; Van Seventer, et. al (2006) Age and Ageing 35:132-137.
- 8Gore, et. al. (2004), 64th Annual Scientific Sessions, American Diabetes Association, Abstract 531-P; Van Seventer, et. al. (2006),Age and Ageing 35:132-137.
- 9Datamonitor, Pipeline and Commercial Insight: Neuropathic Pain, Published June 2008, 28-29
"The two most common types of peripheral neuropathy are painful diabetic neuropathy (PDN) and post-herpetic neuralgia (PHN)."
"There is a significant opportunity to develop novel topical formulations of therapeutics for neuropathic pain that can be applied directly to the site of origin of the pain, while leading to fewer systemic side-effects."