Peripheral neuropathic pain patch treatments: an interview with Anne Hodgkins, Astellas Pharma

Interview conducted by April Cashin-Garbutt, MA (Editor)May 8 2013

What is peripheral neuropathic pain, who does it affect and what causes it?

Peripheral neuropathic pain is caused by lesion or disease to the peripheral somatosensory nervous system. Nerve damage that can lead to peripheral neuropathic pain can happen as a result of a range of different diseases, medications or traumatic injuries.

Exactly how many people suffer from neuropathic pain is not known but estimates of the prevalence of neuropathic pain range from 3% to as high as 8% according to a UK study. Estimates vary considerably because of differences in the way neuropathic pain is defined, the way in which the condition is assessed and the selection of patients.

What treatments have traditionally been used for peripheral neuropathic pain?

Neuropathic pain is considered to be a complex disorder that is difficult to treat. Treatment often involves finding the best balance of pain relief with the fewest side effects and the most effective control of co morbidities.

The Special Interest Group on Neuropathic Pain (NeuPSIG) of the International Association for the Study of Pain (IASP), has published evidence-based guidelines for the pharmacological management of neuropathic pain.

These guidelines recommend certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), anticonvulsants (i.e., gabapentin and pregabalin) and topical lidocaine as first-line treatments.

Opioid analgesics e.g., tramadol are recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances.

Other medications that are generally recommended for third-line use, that could also be used as second-line treatments in some circumstances, include certain antiepileptic and antidepressant medications, mexiletine, N-methyl-D-aspartate receptor antagonists, and topical low-dose capsaicin.

Please can you give an introduction to QUTENZA?

Qutenza (8% capsaicin patch) delivers a high-dose of a synthetic form of capsaicin, the substance found in chilli peppers, directly to the damaged pain sensing nerves in the skin.

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 “defunctionalised”, effectively reducing their spontaneous activity and making them unresponsive to stimuli that normally cause pain for patients with peripheral neuropathic pain.

The 8% capsaicin patch is applied to the area of pain and left in place for either 30 minutes (when used on the feet) or 60 minutes (when used elsewhere on the body). Treatment can be repeated, if required, after 90 days.

Pain relief following application of the 8% capsaicin patch can take up to two weeks to take full effect and can last for up to 12 weeks following a single application.

The patch is indicated for the treatment of peripheral neuropathic pain in non-diabetic adults either alone or in combination with other medicinal products for pain.

The efficacy and safety of the 8% capsaicin patch have been shown in a broad range of neuropathic pain conditions, including post-herpetic neuralgia and HIV-associated neuropathy. Phase-III clinical studies in painful diabetic neuropathy and long-term safety studies are ongoing.

Is the 8% capsaicin patch associated with systemic side effects? How does it compare to conventional therapies for peripheral neuropathic pain?

Conventional therapies for peripheral neuropathic pain can be restricted by factors such as systemic side effects, drug-drug interactions, slow onset of action, the need for titration and multiple daily dosing.

The 8% capsaicin 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.

What pre-treatment was previously needed prior to use of QUTENZA?

Previously, the label stated that the painful area should be pre-treated with a local anaesthetic to minimise any treatment-related discomfort.

Why was this pre-treatment limiting for patients?

The previous pre-treatment involved applying a topical anaesthetic to the entire treatment area and surrounding 1 to 2 cm, and waiting for 60 minutes before applying the 8% capsaicin patch. This was time consuming for patients and physicians.

What pre-treatments have now been approved by the European Commission (EC)?

Now, the treatment area may either be pre-treated with a topical anaesthetic or the patient might be administered an oral analgesic to reduce potential application related discomfort.

For treating clinicians the label change provides greater flexibility to choose a suitable pre-treatment for each patient, enabling them to potentially treat more patients per session.

In which countries is the 8% capsaicin patch label amendment valid?

The EC approval of the 8% capsaicin patch label amendment is valid in all of the 27 European Union Member States plus Iceland, Liechtenstein and Norway.

What data was given to support the regulatory submission?

The regulatory submission was supported by data from the LIFT study, which aimed to investigate the use of an oral analgesic as an alternative form of pre-treatment for the 8% capsaicin patch.

All patients were randomized to one of two arms and pre-treated with either topical anaesthetic (lidocaine cream) or an oral analgesic (tramadol oral tablets). All patients were then treated with the 8% capsaicin patch for 60 minutes and were then followed up for 7 days to monitor pain scores and tolerability.

The LIFT study was completed in April 2012 and the results will be presented at The 4th International Congress on Neuropathic Pain (NeuPSIG) in May 2013.

What impact do you think the approval of these pre-treatments will have on patients with peripheral neuropathic pain?

Managing peripheral neuropathic pain is challenging and the individual needs of the patient are paramount when treatment decisions are made. We are committed to ensuring the 8% capsaicin patch is an accessible and convenient treatment option for physicians and patients. This label amendment allows for a more flexible approach to 8% capsaicin patch treatment, enabling treating clinicians to choose a suitable pre-treatment for each individual patient.

Where can readers find more information?

Healthcare professionals can find out more from http://www.epgonline.org/

About Anne Hodgkins

Originally a microbiologist, Anne’s first entry into the pharmaceutical industry was Janssen Pharmaceuticals, firstly in sales and latterly in various marketing positions working within their anti-fungal, psychiatry and gastroenterology franchises.

She then moved to the UK affiliate of Allergan in a market development role.

From there she became a member of the European Marketing Management Team for BOTOX , responsible for the neurology and neuro-rehabilitation indications.

Latterly, she helped establish their European Medical Affairs Department where her responsibilities included the set-up and management of clinical trials involving BOTOX in the therapeutic areas of incontinence, migraine and spasticity as well as supporting the facial aesthetic team.

As part of her role she was also responsible for developing and maintaining KOL relationships across these specialities and devising educational symposia and training courses for physicians.

In 2008, she joined Astellas Europe Pharma Ltd and for 3 years successfully led the VESICARE brand team, which is the most widely prescribed OAB treatment in Europe.

She is now Senior Brand Director for the Pain franchise.

QUTENZA™ Prescribing Information

PRESCRIBING INFORMATION: QUTENZA™ 179 mg capsaicin cutaneous patch.

ACTIVE INGREDIENT: Capsaicin (640 mcg/cm2, 8% w/w).

PHARMACEUTICAL FORM AND CONTENTS: Each carton contains 1 or 2 sachets each containing 1 cutaneous patch and 1 tube of cleansing gel (50 g). Each patch is 14 cm × 20 cm (280 cm2).

LIST OF EXCIPIENTS: Each patch consists of a matrix containing: silicone adhesives, diethylene glycol monoethyl ether, silicone oil, ethylcellulose N50 (E462); backing layer: polyester backing film, printing ink containing Pigment White 6; removable protective layer: polyester release liner; each 50 g of cleansing gel for QUTENZA contains 0.2 mg/g butylhydroxyanisole (E320), disodium edetate, sodium hydroxide (E524), purified water; carbomer; polyethylene glycol.

THERAPEUTIC INDICATIONS: QUTENZA is indicated for the treatment of peripheral neuropathic pain in non-diabetic adults either alone or in combination with other medicinal products for pain.

DO NOT USE: If the patient is allergic (hypersensitive) to capsaicin, chilli peppers or any other ingredients in the QUTENZA cutaneous patch. Do not use QUTENZA on any part of the patient’s head or face. Do not use QUTENZA on broken skin or open wounds. Do not touch QUTENZA or any other materials that have come into contact with treated areas as it may cause burning and stinging. Do not touch your eyes, mouth or other sensitive areas. Sniffing or inhaling close to the QUTENZA patches may cause coughing or sneezing.

USE IN CHILDREN AND ADOLESCENTS: QUTENZA is not recommended for treatment in patients under 18 years of age.

PREGNANCY AND LACTATION: Caution should be exercised when prescribing to pregnant women. Breastfeeding should be discontinued during treatment with QUTENZA.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: QUTENZA has no or negligible influence on the ability to drive and use machines.

DOSAGE AND METHOD OF USE: QUTENZA should be administered by a healthcare professional. The treatment area may be pre-treated with a topical anaesthetic or the patient might be administered an oral analgesic prior to application of QUTENZA to reduce potential application-related discomfort. QUTENZA should be applied to the most painful skin areas (using up to a maximum of 4 patches). QUTENZA must be applied to intact, non-irritated dry skin, and allowed to remain in place for 30 minutes for the feet (e.g. HIV-associated neuropathy) and 60 minutes for other locations (e.g. post-herpetic
neuralgia). QUTENZA treatments may be repeated every 90 days, as warranted by the persistence or return of pain. Full details of QUTENZA administration are given in the Summary of Product Characteristics.

ADVERSE REACTIONS: The most commonly reported adverse reactions were transient local application site burning, pain, erythema and pruritis. Adverse reactions were transient, self-limited and usually mild to moderate in intensity. There have been reported cases of burns, including second degree burns, in patients treated with capsaicin patches. In patients reporting severe pain, the patch should be removed and the skin examined for chemical burn. See Summary of Product Characteristics for details.

PRECAUTIONS FOR USE: In case of unstable or poorly controlled high blood pressure or recent heart problems, the physician should consider risk of adverse reactions to heart or blood pressure as a result of procedure. Nitrile gloves should be worn at all times while handling QUTENZA and cleaning treatment areas. QUTENZA patches should not be held near eyes or mucous membranes. Direct contact with QUTENZA, used gauze or used cleansing gel should be avoided. The cleansing gel for QUTENZA contains butylhydroxyanisole which may cause local skin reactions, e.g. contact
dermatitis or irritation of the eye and mucous membranes.

CONTRAINDICATIONS: Hypersensitivity to the active substance or any of the excipients.

INTERACTIONS: No formal interaction studies with other medicinal products have been performed as only transient low levels of systemic absorption have been known to occur with QUTENZA.

PACKAGE SIZE: Each QUTENZA carton contains 1 or 2 QUTENZA treatment sachets and 1 tube of cleansing gel (50 g). Not all pack sizes may be marketed.

SPECIAL STORAGE CONDITIONS: Store flat in original sachet and carton. Store below 25°C.

SPECIAL PRECAUTIONS FOR DISPOSAL: Dispose of unused patches, gauze wipes and all other materials placed in contact with treated area by sealing in a polyethylene bag and placing in an appropriate medical waste container.

SPECIAL WARNINGS: Keep out of the sight and reach of children.

EXPIRY DATE: Unopened sachet: 4 years. After opening sachet: apply QUTENZA within 2 hours.

LEGAL CATEGORY: POM.

MARKETING AUTHORISATION NUMBERS: EU/1/09/524/001-002.

FURTHER INFORMATION AVAILABLE FROM: Astellas Pharma Europe Ltd., 2000 Hillswood Drive, Chertsey, KT16
0RS, United Kingdom.

DATE OF REVISION: 15 February 2013.

FOR FULL PRESCRIBING INFORMATION REFER TO THE SUMMARY OF PRODUCT CHARACTERISTICS.

As prescribing information may vary from country to country, see local prescribing information for full details.

Adverse events should be reported. Report adverse events to Astellas Pharma Europe by email to [email protected], by facsimile to +31 (0)71-545 5208, or contact your local Astellas office (www.astellas.eu/contact/locations/).

© November 2009–February 2013 Astellas Pharma Europe Ltd.
Unless otherwise stated, trademarks are owned by Astellas Pharma Inc. and/or its related entities. Trademarks may also be used under license and/or by permission of originator companies.