Grünenthal’s Phase III RISE trial found significant average pain reduction with Qutenza over weeks 2–12, but not at Week 12 alone.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
Grünenthal has reported Phase III results from the RISE trial evaluating Qutenza (capsaicin 8% topical system) in adults with moderate-to-severe post-surgical neuropathic pain. The study met one of its two primary efficacy endpoints, demonstrating a statistically significant reduction in average pain intensity over weeks 2–12 compared with a low-dose capsaicin control patch.
However, the difference at Week 12 alone did not reach statistical significance. The findings were presented as late-breaking posters at the 2026 International Association for the Study of Pain (IASP) World Congress on Pain.
RISE Trial Design and Patient Population
RISE (NCT04967664), also known as AV001, was a multicentre, randomised, double-blind, parallel-group Phase III trial sponsored by Averitas Pharma, Grünenthal’s US subsidiary. The study evaluated Qutenza in adults experiencing moderate-to-severe neuropathic pain lasting 6–60 months after surgery.
Eligible participants had a 24-hour average pain intensity (API) score of at least 4 and a Douleur Neuropathique 4 (DN4) interview score of at least 3. Participants received either Qutenza 179 mg, containing capsaicin 8%, applied for 60 minutes, or a low-dose capsaicin 0.04% control patch.
The trial assessed changes in API from baseline to the average score over weeks 2–12 and to the Week 12 score. An extension phase evaluated outcomes through Week 42, allowing up to four additional treatments.
Average Pain Reduction Met One Primary Endpoint
Grünenthal reported that Qutenza achieved a statistically significantly greater reduction in average API than the control treatment across weeks 2–12. This met one prespecified primary endpoint, supporting a treatment effect across the assessment period.
The separate Week 12 endpoint, however, did not reach statistical significance, although the numerical difference favoured Qutenza. The distinction is important because the trial did not meet both primary endpoints. A positive average-period result does not establish a statistically significant treatment difference at the specific Week 12 assessment.
Grünenthal’s development pipeline identifies the two analyses as addressing differing regulatory expectations. The weeks 2–12 analysis aligned with European Medicines Agency guidance, whereas the Week 12 analysis addressed the US Food and Drug Administration’s expectations. [2]
Extension Findings and Safety
In the extension phase, Qutenza produced a statistically significantly greater reduction in API than the control treatment over weeks 2–42, according to the company. The findings suggest that the difference in pain reduction was maintained over the longer observation period with repeat treatment. However, the announcement does not provide numerical treatment differences or confidence intervals, limiting assessment of the magnitude and precision of the benefit.
Grünenthal reported that the safety profile was consistent with previous Qutenza trials and that no new safety signals were identified. These findings are reassuring at the topline level, but the company’s announcement does not provide detailed adverse-event rates for comparing tolerability between treatment groups.
Regulatory Implications
Qutenza is already approved in Europe for peripheral neuropathic pain in adults, alone or in combination with other pain medicines. In the United States, its approved indications include postherpetic neuralgia and diabetic peripheral neuropathy of the feet in adults. The RISE findings concern post-surgical neuropathic pain and do not themselves establish a new approved indication.
Grünenthal states that the AV001 results will support regulatory submissions intended to expand Qutenza’s availability, including an update to the European Summary of Product Characteristics. The company has also stated that it will not pursue a supplemental New Drug Application with the FDA based on this trial. This divergence reflects the different outcomes of the two primary endpoint analyses and is an important consideration in assessing the programme’s regulatory prospects.
Clinical Interpretation
RISE provides Phase III evidence of a statistically significant reduction in average pain intensity over weeks 2–12 with Qutenza compared with a low-dose capsaicin control. The non-significant Week 12 result tempers the overall interpretation, while the extension findings suggest a sustained difference through Week 42 with repeat treatment.
The results should not be interpreted as demonstrating superiority over other neuropathic-pain therapies because the study used a low-dose capsaicin control rather than an active alternative treatment. Although the company has outlined potential European regulatory follow-up, the findings do not establish an expanded indication or resolve the uncertainty around the Week 12 endpoint. The full registry results and eventual peer-reviewed publication will be important for assessing the treatment effect, its precision and the detailed safety profile.
References
Grünenthal presents Phase III results for Qutenza in post-surgical neuropathic pain at IASP 2026 World Congress on Pain. Grünenthal, October 28, 2026
Comparison of Qutenza (8% Capsaicin) With a Low-dose Capsaicin for Treatment of Nerve Pain After Surgery (RISE), ClinicalTrials.gov ID NCT04967664
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.