Nuvo Announces Results from European Ankle Sprain Study with Pennsaid 2%

Nuvo Pharmaceuticals reported topline results from its multi-center, randomized, placebo-controlled, double-blind, parallel group trial in patients, with grade I or II ankle sprains and in particular reported that the Trial had failed to meet its primary endpoint.

The trial was conducted in Germany and enrolled 134 patients (the full analysis set or FAS) of which 122 patients followed the protocol who had suffered a grade I or grade II ankle sprain as assessed by the investigator within 12 hours of injury. Patients were randomly assigned on a double-blind basis to an active arm or a control arm and applied either Pennsaid 2% or a control consisting of a topical vehicle that includes all the constituent ingredients of Pennsaid 2%, except its active ingredient diclofenac sodium to their injured ankle twice a day for 8 days. The patients returned to the investigational site for in-depth evaluation on days 3, 5 and 8 of treatment. The primary endpoint for the trial was reduction in pain on movement (POM) at day 3. The trial also measured a number of secondary endpoints including ankle function, meaningful improvement in pain on movement, overall assessment of benefit and satisfaction, tenderness and ankle swelling.  Patients also filled out a daily diary that recorded their answers to a number of standardized questions related to the negative impact of the injury on sleep and daily activities.  The trial commenced in November 2016 and was fully enrolled in March 2017.

The primary endpoint for the trial was reduction in pain on movement (POM) at day 3 in the FAS group.  On average, patients treated with Pennsaid 2% had a larger reduction in POM scores over the course of the study.  For the FAS group, the difference vs. Control was not statistically significant at the primary time point at day 3 (p=0.5074) or the secondary time point at day 5 (p=0.1642); however, was statistically significant at the secondary time point at day 8 (p=0.0099).  In the PP group, the Pennsaid 2% group did not show a statistically significant improvement at day 3 (p=0.6996) or day 5 (p=0.1865), but did show a statistically significant improvement at day 8 (p=0.0154).

The trial also included the measure of a number of secondary endpoints, which included ankle function.  Pennsaid 2% demonstrated a statistically significant increase in ankle function compared to Control in the FAS group at days 3, 5 and 8 with p-values of 0.0383, 0.0072 and 0.0055, respectively. Pennsaid 2% also demonstrated a statistically significant meaningful improvement in POM compared to Control in the FAS group at day 5 (p=0.0444) but not at day 3 (p=0.4127) or day 8 (p=0.0961).

Patients treated with Pennsaid 2% reported a statistically significantly higher level of satisfaction with and benefit of their treatment compared to Control in the FAS group at day 8 with a p-value of 0.0164 for the treatment benefit and a p-value of 0.0499 for satisfaction; however, did not report a statistically higher level of satisfaction and benefit of their treatment compared to Control at days 3 (p=0.2464 and p=0.1389 for benefit and satisfaction, respectively) or at day 5 (p=0.1974 and p=0.2548 for benefit and satisfaction, respectively).

Pennsaid 2% did not demonstrate a statistically significant reduction in tenderness compared to Control in the FAS group at days 3, 5 and 8 with p-values of 0.1776, 0.4870 and 0.9013, respectively. Additionally, Pennsaid 2% did not demonstrate a statistically significant decrease in ankle swelling compared to Control in the FAS group at days 3, 5 and 8 with p-values of 0.1150, 0.7980 and 0.1042, respectively.

Pennsaid 2% is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of the pain of osteoarthritis (OA) of the knee(s).  It is also approved by the Russian Ministry of Health for non-prescription human use in treating back pain, joint pain, muscle pain, and inflammation and swelling in soft tissue and joints associated with trauma and rheumatic conditions. The trial was conducted to support regulatory applications for marketing approval of Pennsaid 2% for the treatment of acute pain in the E.U., Canada and Australia which are potential new markets for Pennsaid 2%.  The company believes that most other jurisdictions will base their marketing approval on existing data, including the current U.S. FDA approval of Pennsaid 2% and will not require additional clinical efficacy data. 

The trial results will not affect the marketing and sale of Pennsaid 2% in the U.S. where it is approved by the FDA for the treatment of the pain of OA of the knee(s) or in Russia where it is approved for non-prescription human use of Pennsaid 2% in treating back pain, joint pain, muscle pain, and inflammation and swelling in soft tissue and joints associated with trauma and rheumatic conditions.

"We are obviously disappointed by the Trial results," John London, CEO of Nuvo said. "Although the trial did not achieve its primary endpoint of reduction in pain on movement at day 3, we saw positive indications in the secondary endpoints, as well as in the patient diaries that Pennsaid 2% is beneficial in the treatment of patients with ankle sprains.  We will continue to assess the opportunities available to us to pursue marketing authorizations for Pennsaid 2% in Canada, Australia and the E.U."