A Phase III trial in post-surgical neuropathic pain just produced a split result, and the distinction matters for how the data will be used. In the 409-patient RISE trial, Qutenza (capsaicin 8% patch) reduced average pain intensity significantly more than a low-dose capsaicin control patch across weeks 2 through 12, meeting one of its two pre-specified primary endpoints. But at week 12 alone, the point when patients would typically return for retreatment, the numerical difference favored Qutenza without reaching statistical significance. Grünenthal presented the findings as a late-breaking poster at the IASP World Congress on Pain in Bangkok this week.
The extension-phase result carries more weight for the clinical picture. Patients who continued into the extension, where up to four retreatments were permitted, showed a statistically significant reduction in average pain intensity over weeks 2 through 42. That is roughly ten months of sustained benefit in a population where, as the trial’s entry criteria specify, pain had already persisted between six and sixty months after surgery. Eligible participants needed an average pain score of at least 4 out of 10 and a DN4 interview score of 3 or higher, selecting for a meaningfully symptomatic group. No new safety signals appeared, consistent with Qutenza’s existing European label, where it is approved for peripheral neuropathic pain in adults.
Post-surgical neuropathic pain is common and persistently underdiagnosed. Research in the field estimates chronic post-surgical pain affects somewhere between 10% and 50% of operated patients, with a neuropathic component in a meaningful subset. Current management often defaults to systemic analgesics or off-label agents that carry their own tolerability problems. Qutenza’s mechanism, temporarily defunctionalizing TRPV1-expressing nociceptors with a single application, sidesteps systemic exposure. That profile is the commercial rationale Averitas Pharma, Grünenthal’s U.S. subsidiary and the trial’s primary sponsor, would lean on in any regulatory submission, though the U.S. label currently covers postherpetic neuralgia and diabetic peripheral neuropathy of the feet, not post-surgical pain.
The failure to reach statistical significance on the week-12 co-primary endpoint is the result regulators will scrutinise most closely. A durable treatment effect across the extension is encouraging, but the retreatment interval endpoint is what a label expansion for post-surgical pain would need to anchor on. Whether Grünenthal files for that expansion, and in which jurisdiction first, is the question the RISE data now put squarely on the table.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
