First participants enrolled in Clinical Trial with Nociceptin/Orphanin peptide receptor (NOP) agonist

Aachen, Germany, 29 September 2021 –Today, Grünenthal announced that the first participants have been enrolled in a randomised, placebo- and active-controlled clinical trial for its peripherally restricted Nociceptin/Orphanin FQ peptide receptor (NOP) agonist. The compound is being developed to provide a non-opioid therapy option that offers a strong analgesic effect without the side effects commonly associated with opioids. The Experimental Medicine Trial will evaluate the extent and duration of the pharmacological effect of the oral NOP agonist in an experimental pain model. The results of the trial are expected to be available in early 2022.

The trial explores how the NOP agonist influences pain signalling and perception using laser evoked potentials (LEPs) in an experimental pain model with 30 healthy participants. On five different occasions, the participants will receive either the NOP agonist or pregabalin or placebo. The trial explores three different doses of the NOP agonist; pregabalin and placebo will be given to ensure control conditions. In the experimental pain model, a laser will generate a short tolerable painful heat stimulus on the participant’s skin which has been sensitised to mimic a temporary state of neuropathic pain. Both objective and subjective endpoints will be assessed in response to the laser stimuli, including electroencephalography (EEG) to measure brain activity and the Visual Analogue Scale (VAS) for subjective pain perception.

”This peripherally restricted, potent and selective NOP receptor agonist has shown analgesic effects in a wide range of pre-clinical pain models^[1],” says Jan Adams, M.D., Chief Scientific Officer Grünenthal. “Millions of patients suffer from chronic neuropathic pain and are in need of better treatment options. With its unique mechanism of action, our NOP agonist may have the potential to provide these patients with a therapeutic benefit and an improved safety profile compared to the available standards of care.”

A First-in-Human clinical trial to assess the safety and tolerability profile and the pharmacokinetic characteristics of the NOP agonist is ongoing since December 2020. In addition, Grünenthal intends to start a Phase IIa trial to evaluate the compound’s efficacy in patients with painful diabetic peripheral neuropathy in 2022.

Grünenthal’s R&D pipeline includes multiple programmes across different targets, modalities and mechanisms of action to deliver better treatments for patients with severe pain conditions. In addition to developing its NOP agonist, Grünenthal is conducting a Phase I clinical trial with a Glucocorticoid Receptor Modulator (GRM) aiming to provide patients with a therapy option for chronic inflammatory diseases. Grünenthal recently announced the start of recruitment for a Phase III clinical trial with Qutenza® (capsaicin) 8% topical system in post-surgical neuropathic pain. In addition, Grünenthal intends to enrol the first patients with painful osteoarthritis of the knee in a Phase III clinical trial to investigate the efficacy, safety and tolerability of Resiniferatoxin by Q1 2022.

[1] Grünenthal Data on file