Head-to-Head Study Will Compare Qutenza and Pregabalin in the Treatment of Peripheral Neuropathic Pain
ELEVATE Study First to Compare Efficacy, Tolerability and Impact on Quality of Life Versus Pregabalin
SAN MATEO, Calif., July 24, 2012 (GLOBE NEWSWIRE) -- NeurogesX, Inc. (OTCQB:NGSX) (OTCBB:NGSX), a specialty pharmaceutical company focused on developing and commercializing a portfolio of novel non-opioid, pain management therapies, announced today that its partner Astellas Pharma Europe Ltd., the European headquarters of Tokyo-based Astellas Pharma Inc., has enrolled the first patient in its ELEVATE clinical trial in the European Union (EU). This trial is the first study to compare Qutenza® (8% capsaicin patch) to pregabalin as a treatment for peripheral neuropathic pain. Pregabalin is an oral therapy widely used as first-line treatment for peripheral neuropathic pain.[i] Under its Commercial License Agreement with Astellas, NeurogesX shares in the growing market opportunity for Qutenza in the Astellas territory, which includes the EU, the Middle East and Africa, through ongoing royalties, as well as potential sales milestones. In the United States, Qutenza is approved for the management of neuropathic pain associated with post herpetic neuralgia (PHN).
The earliest results of the ELEVATE study, which will evaluate the efficacy and safety of the Qutenza topical patch against pregabalin, are expected in 2014.
Conventional therapies for peripheral neuropathic pain have been limited by negative factors such as systemic side effects, drug-drug interactions, slow onset of action, the need for titration and multiple daily dosing.[ii],[iii],[iv] The Qutenza patch is designed to act locally on the affected area and has not been associated with the systemic side effects such as sedation and dizziness that may be experienced with other treatments.[ii],[iii],[v] The ELEVATE study is designed to evaluate which therapy better balances pain relief with tolerability and the ability to return to daily activities.
Associate Professor Maija Haanpää, a Consultant in Pain Management at the Helsinki University Central Hospital, Finland and the lead investigator in the ELEVATE study, commented, "It is important to perform head-to-head comparative studies, such as this one, in the field of neuropathic pain. The ELEVATE study may also provide information about the symptom profiles that are most likely to respond to the different treatments since the NPSI* questionnaire, given during the trial, will be used to assess the characteristics of pain and other sensory symptoms."
The study aims to enroll 526 patients from approximately 100 centers in 23 countries across eastern and western Europe, including the UK, Germany, France, Italy, Spain, Sweden, Finland, Russia, Romania and Bulgaria.[i]
Qutenza uses a synthetic form of capsaicin, the substance found in chili peppers which gives them their 'heat,' to change the way pain-sensing nerves work in the treated area.[vi] The efficacy and safety of Qutenza have already been investigated in a comprehensive clinical trial program involving 1,327 patients who received at least one application.[v] Pain relief following application of the 8% capsaicin patch can take up to two weeks to take full effect and can be maintained for up to twelve weeks following a single application.[v] Qutenza has caused significant pain reduction when used alone or in combination with other treatments for pain.[v]
The most commonly reported side effects for Qutenza are transient and self-limiting application site reactions, such as pain and erythema that tend to be mild to moderate in intensity.[v]
While the number of patients who suffer from neuropathic pain is not known, estimates typically range from 1 to 2% of the [global] population, while some sources estimate prevalence to be as high as 8%.[vii],[viii] Peripheral neuropathic pain is a complex and difficult to treat disorder that can have a detrimental effect on a patient's quality of life.[ix],[x] Studies suggest that, at present, only one third of patients receiving treatment for neuropathic pain achieve adequate pain relief.[xi] Peripheral neuropathic pain is caused by lesion or disease to the peripheral somatosensory nervous system. The somatosensory system is a diverse sensory system composed of the receptors and processing centers to provide information about touch or pressure, temperature, body position and pain. The nerve damage that can lead to peripheral neuropathic pain can happen as a result of a range of different diseases, medications or traumatic injuries.
*The Neuropathic Pain Symptom Inventory (NPSI) is self-questionnaire specifically designed to evaluate the different symptoms of neuropathic pain.
About the ELEVATE study
ELEVATE is an open-label study that is planned to enroll 526 adult subjects with moderate-to-severe peripheral neuropathic pain (baseline diagnosis of post-herpetic neuralgia, peripheral nerve injury, or non-diabetic painful peripheral polyneuropathy).[i] Patients in the trial will randomly receive either a single application of up to four 8% capsaicin patches or daily administration of an optimal dose of oral pregabalin (up-titration from 75 mg/day to 150–600 mg/day) for 8 weeks. Patients enrolled into the study will be either naive to treatment with 8% capsaicin patch, pregabalin and gabapentin or will not have previously received an adequate trial or treatment with pregabalin or gabapentin. The study will include the following key endpoints: [i]
- The level of pain relief, as measured by the proportion of subjects in each arm who achieve at least a 30% decrease in the 'average pain for the past 24 hours' Numeric Pain Rating Scale score from baseline to Week 8.
- The overall therapeutic effect; assessed using a composite endpoint which includes pain relief, adverse events and treatment discontinuation.
About Qutenza
Qutenza® (capsaicin) 8% patch is approved by the European Medicines Agency for the treatment of peripheral neuropathic pain in non-diabetic adults either alone or in combination with other medicinal products for pain. [v] The 8% capsaicin patch is available in 21 countries across Europe as of the end of 2011. Phase 3 clinical studies in painful diabetic neuropathy (PDN) and long-term safety studies are ongoing. Qutenza is approved by the U.S. Food and Drug Administration (FDA) for the management of neuropathic pain associated with postherpetic neuralgia (PHN).
The patch delivers a high-dose of a synthetic form of capsaicin directly to the damaged pain sensing nerves in the skin that are the source of neuropathic pain. Applied to the area of pain, the high concentration of capsaicin contained in the treatment is released into the skin where it overstimulates the pain sensing nerves. Overstimulating the pain sensing nerves makes them become "defunctionalized," effectively reducing their spontaneous activity and making them unresponsive to stimuli that normally cause pain for patients with peripheral neuropathic pain.[xii]
About Astellas Pharma Europe Ltd.
Astellas Pharma Europe Ltd., located in the UK, is the European headquarters of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. The organisation is committed to becoming a global company by combining outstanding RD and marketing capabilities and continuing to grow in the world pharmaceutical market. Astellas Pharma Europe Ltd. is responsible for 21 affiliate offices located across Europe, the Middle East and Africa, an RD site and three manufacturing plants. The company employs approximately 4,200 staff across these regions. For more information about Astellas Pharma Europe, please visit www.astellas.eu.
About NeurogesX
NeurogesX, Inc. (OTCQB:NGSX) (OTCBB:NGSX) is a specialty pharmaceutical company focused on developing and commercializing a portfolio of novel non-opioid, pain management therapies to address unmet medical needs and improve patients' quality of life.
The Company's lead product, Qutenza®, is currently approved in the United States and the European Union. Qutenza® is now available in the United States for the management of neuropathic pain associated with postherpetic neuralgia (PHN). In Europe, Qutenza® is being marketed by Astellas Pharma Europe Ltd. (Astellas), the European affiliate of Tokyo-based Astellas Pharma Inc., for the treatment of peripheral neuropathic pain in non-diabetic adults, either alone or in combination with other medicinal products for pain.
The Company's most advanced product candidate, NGX-1998, is a topically applied liquid formulation containing a high concentration of capsaicin designed to treat pain associated with neuropathic pain conditions such as PHN. NGX-1998 has completed three Phase 1 clinical trials and one Phase 2 clinical trial in PHN patients, and the Company believes that NGX-1998 is ready to enter Phase 3 development.
The Company's early-stage pipeline includes pre-clinical compounds which include a number of prodrugs of acetaminophen. The Company has evaluated certain of these compounds in vitro and in vivo.
Safe Harbor Statement
This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the Act). NeurogesX disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Safe Harbor for forward-looking statements contained in the Act. Examples of such statements include but are not limited to statements regarding: expected timing of earliest results in 2014 for the ELEVATE study; and NGX-1998 being ready for entry into Phase 3 development. Such statements are based on management's current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to: difficulties or delays in carrying out further clinical testing for Qutenza, including difficulties in enrolling patients; NGX-1998 may fail to demonstrate sufficient safety or efficacy in clinical trials to support further development or potential marketing approval; difficulties or delays in further clinical development of NGX-1998, including difficulties or delays in initiating Phase 3 clinical trials; adverse outcomes with respect to, or delay of, the End-of-Phase 2 meeting with the FDA; market acceptance of Qutenza in already approved indications may not be sufficient to support further pursuit of commercialization of Qutenza or could have an effect on NeurogesX' development or other plans with respect to NGX-1998; Qutenza, NGX-1998 and NeurogesX' other product candidates may have unexpected adverse side effects; delay or prevention of commercialization or development activities due to unexpected expenses or a lack of sufficient resources; and difficulties or delays in identifying potential strategic partners for Qutenza and NGX-1998 and negotiating and entering into agreements with such entities. For further information regarding these and other risks related to NeurogesX' business, investors should consult NeurogesX' filings with the Securities and Exchange Commission.
References
[i] EU Clinical Trials Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-005872-41Last accessed: May 2012
[ii] Backonja M et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol 2008;7(12):1106-12
[iii] Simpson DM et al. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology 2008;70(24):2305-13
[iv] O'Connor AB et al. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med 2009;122:S22-32
[v] Qutenza (Capsaicin) EPAR. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000909/WC500040453.pdf Last accessed: April 2012
[vi] Knotkova H et al. Capsaicin (TRPV1 agonist) therapy for pain relief: Farewell or revival? Clin J Pain 2008;24(2):142-154
[vii] National Institute for Health and Clinical Excellence (NICE) Neuropathic Pain: The pharmacological management of neuropathic pain in adults in non-specialist settings. March 2010. Available from: http://www.nice.org.uk/nicemedia/live/12948/47949/47949.pdf. Last accessed: April 2012
[viii] Mailis Gagnon A et al. Systematic review of the prevalence of neuropathic pain. Eur J Pain 2007;11 (Suppl. 1):S202-S203 [Abstract No. 457]
[ix] Gálvez R et al. Cross-sectional evaluation of patient functioning and health-related quality of life in patient with neuropathic pain under standard care conditions. Eur J of Pain 2007;3:244-55
[x] Smith B et al. Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community. Clin J Pain 2007;23:143–9
[xi] Jensen T et al. Pharmacology and treatment of neuropathic pains. Current Opinion in Neurology 2009;22:467-474
[xii] Anand P et al. Topical capsacin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth 2011;107(4):490-502