P-040 - (Poster #40) Opioid sparing effect of MR-107A-02 (novel fast-acting meloxicam formulation) for the treatment of acute moderate-to-severe pain following bunionectomy and herniorrhaphy

Opioids have long been considered as the mainstay in the management of acute moderate-to-severe pain. While these drugs effectively reduce pain and help in achieving patient outcomes, they are associated with certain risks, including respiratory depression, tolerance, overdose, dependence and death. The U.S. opioid crisis remains a pressing public health concern. According to the Centers for Disease Control and Prevention (CDC), drug overdose deaths decreased by 27% in 2024 compared to 2023 (from 110,037 deaths estimated in 2023 to an estimated 80,391 drug overdose deaths in the U.S. during 2024), marking a significant improvement. Despite this, opioid-related deaths remain the leading cause of death for Americans aged 18–44 years. The CDC continues to emphasize the importance of preventing unnecessary opioid exposure, especially after surgery.
Additionally, in 2016 a joint clinical practice guideline issued by the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia recommended incorporating the non-opioid drugs and other analgesic measures into pain management strategies, in an effort to reduce opioid consumption and improve outcomes for patients.

Purpose/Objectives:

MR-107A-02 is a novel formulation of meloxicam currently being developed by Viatris. This fast-acting formulation is designed to ensure rapid absorption and deliver clinical analgesic benefits comparable to conventional oral meloxicam formulations. To evaluate the efficacy, safety and opioid sparing effect of MR-107A-02, well-researched and established pain models were used. We analyzed the opioid sparing effects of MR-107A-02 in bony and soft tissue surgery models, namely bunionectomy and herniorrhaphy. These models are ideal for assessing the analgesic effects, as they exhibit good sensitivity, induce acute moderate-to-severe pain, and are considered representative of acute pain states in general by regulatory agencies. Two phase III studies were designed to assess the efficacy and safety of MR-107A-02 in the reduction of acute moderate-to-severe pain in patients undergoing bunionectomy and herniorrhaphy. Additionally, we evaluated the opioid-sparing effect of MR-107A-02 in the above-mentioned studies.

Methods:

Both the bunionectomy and herniorrhaphy studies were multi-center, randomized, double-blind, double-dummy, placebo- and active-controlled, parallel group trials conducted in the United States.

Patients experiencing the required level of pain (score ≥4 on an 11-point numeric rating scale-rest [NRS-R] and/or NRS-activity [NRS-A] where 0 = no pain to 10 = worst possible pain) after bunionectomy and/or herniorrhaphy were randomized to receive MR-107A-02 15 mg (BID), placebo, or tramadol 50 mg (QID) at 1:1:1 and 2:2:1 ratio, respectively.

In both studies, comparisons between MR-107A-02 and placebo included the number and proportion of subjects using acetaminophen and opioid (oxycodone and/or morphine) rescue medication, the mean number of doses, number of times of usage, time to first opioid use, and proportion of opioid free subjects. The studies were approved by Institutional Review Board (IRB) and informed consent was obtained from all participants.

Results:

Of 410 randomized participants (137 MR-107A-02, 136 placebo,137 tramadol; 85.9% females; 60% whites; mean [SD] age, 48 [13.4] years; weight range, 45-126 kg), 397 participants completed the bunionectomy study. The baseline NRS-R (mean [SD]) were similar across all three groups (7.2 [1.67] MR-107A-02, 7.6 [1.73] placebo, 7.2 [1.64] tramadol).

In the herniorrhaphy study, 579 participants were randomized (232 MR-107A-02, 231 placebo,116 tramadol; 96.3% males; 84 % whites; mean [SD] age, 49.1 [12.21] years; weight range, 44-152 kg), and 551 participants completed the study. The baseline NRS-A (mean [SD]) were similar across all three groups (7.8 [1.66] MR-107A-02, 7.7 [1.68] placebo, 7.8 [1.57] tramadol).

In the bunionectomy study, MR-107A-02 group had 24% more opioid-free patients compared to placebo (78 [56.9%] vs. 45 [33.1%]) with a significant difference in proportions (95% [CI]) (23.8% [12.4, 35.3], p< 0.001). MR-107A-02 showed a 59% lower mean opioid rescue use vs. placebo (mean [SD]) (1.3 [2.16] vs. 2.9 [3.64] doses) with a significant ratio of LS geometric mean vs. placebo (95% [CI]) (0.41 [0.29, 0.58], p< 0.001 ). Additionally, MR-107A-02 had fewer patients requiring opioid rescue (60 [43.8%] MR-107A-02, 92 [67.6%] placebo, 77 [56.2%] tramadol) or any rescue medication (110 [80.3%] MR-107A-02, 128 [94.1%] placebo, 127 [92.7%] tramadol), and the longest median time (hours) to first opioid or any rescue medication compared to placebo and tramadol groups. Similarly, in the herniorrhaphy study, MR-107A-02 group had 14% more opioid-free patients compared to placebo (167 [72.6%] vs. 133 [58.6%]) with a significant difference in proportions vs. placebo (95% [CI]) (14.0% [5.4, 22.6], p= 0.002). MR-107A-02 showed a 35% lower opioid use vs. placebo (mean [SD]) (0.89 [2.17] vs. 1.25 [2.14] doses) with the ratio of LS geometric mean vs. placebo (95% [CI]) (0.65 [0.44, 0.98], p= 0.039). The MR-107A-02 also had fewer patients requiring opioid rescue (65 [28.3%] MR-107A-02, 93 [41.0%] placebo, 36 [31.3%] tramadol) or any rescue medication (128 [55.7%] MR-107A-02, 173 [76.2%] placebo, 76 [66.1%] tramadol) and the longest median time (hours) to first rescue medication compared to placebo and tramadol groups.

Conclusions/Implications for future research and/or clinical care: MR-107A-02 15 mg BID demonstrated a significant opioid-sparing effect across both studies. Compared to placebo, it resulted in the lower mean number of opioid and/or any rescue medication doses and fewer participants requiring such medications. Notably, 57% and 73% of the patients in the meloxicam group were opioid-free in the bunionectomy and herniorrhaphy studies, respectively.