Grunenthal Submits European Marketing Authorisation Application For Centrally Acting Analgesic Tapentadol

Main Category: Pain / Anesthetics
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 07 May 2009 - 0:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

German pain expert Grunenthal GmbH announced that it has submitted the Marketing Authorisation Application (MAA) for tapentadol prolonged- and immediate-release (PR/IR) tablets to several European authorities including BfArM (Germany) who will act as Reference Member State for the Decentralised Procedure (DCP). Grunenthal is seeking an indication for the treatment of severe acute and severe chronic pain requiring centrally acting analgesics therapy in adults 18 years and older. Tapentadol will be the first of a new generation of centrally-acting analgesics for more than 25 years after successful registration in Europe. In the United States, the IR formulation of tapentadol was approved by the Food and Drug Administration (FDA) on November 20, 2008 for the relief of moderate to severe acute pain in patients 18 years of age or older.

The submission is based on data from 22 trials involving approximately 7,200 patients treated with the PR and IR tablet; 3,600 patients for each formulation. The studies were conducted in more than 30 countries to prove efficacy, safety and tolerability in patients with acute and chronic moderate to severe pain by using nociceptive and neuropathic pain models with treatment duration of up to one year.

Overall tapentadol demonstrates comparable efficacy (Numeric Rating Scale, Visual Analogue Scale) to oxycodone, a strong classical opioid, in nociceptive pain with an improved tolerability related to opioid-induced side effects. Additionally, tapentadol shows efficacy in diabetic peripheral neuropathy proven in a placebo-controlled trial. Tapentadol exhibits a better tolerability profile compared to oxycodone sustained release in comparable dosages with reduced opioid-induced GI side effects such as nausea, vomiting, constipation and also a better CNS side effect profile regarding dizziness, somnolence, and pruritus.

"Many patients suffer from pain because available treatment options do not provide sufficient pain relief, or have other limitations such as gastro-intestinal side effects that may trigger patients to discontinue treatment", says Wolfgang Becker, Corporate Executive Board Member - Global Commercial Operations. "We are convinced that tapentadol has the potential to contribute to overcoming these unmet medical needs and therefore help to improve pain management."

Tapentadol is the first of a new generation of centrally-acting analgesics with two mechanisms of action, combining µ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule. It has been shown in animal studies that both mechanisms contribute to the analgesic effects of tapentadol. As the affinity of tapentadol to the µ-opioid receptor is lower compared to classical opioids, the rate of opioid-receptor triggered side effects at comparable analgesic efficacy is reduced.

About Tapentadol

Tapentadol has been under development with an immediate-release (IR) formulation for severe acute pain and a prolonged release (PR) formulation for severe chronic pain. In the United States, the IR formulation of tapentadol was approved by the Food and Drug Administration (FDA) on November 20, 2008 for the relief of moderate to severe acute pain in patients 18 years of age or older. Grunenthal is also preparing the submission of tapentadol to regulatory authorities in Mexico, South America and Australia.

Two Mechanisms of Action

Tapentadol has a unique profile with two mechanisms of action, combining µ-opioid receptor agonism and noradrenaline reuptake inhibition properties in a single molecule. Preclinical studies suggest that both mechanisms contribute to the analgesic effects of tapentadol. Μu-receptor agonists are drugs which act at different levels in the pain pathway, by inhibiting the transmission of the pain signal, the emotional aspect of pain and pain realisation. In addition, the analgesic effect can be explained by the descending inhibition arising from the noradrenaline reuptake inhibition of tapentadol leading to increased noradrenaline levels in the central nervous system.

Source
Grunenthal