Opioid-free Management of Moderate-to-Severe Acute Pain With Suzetrigine

Todd Bertoch¹, Dominick D’Aunno², Jessica McCoun³, Daneshvari Solanki⁴, Louise Taber⁵, Joshua Urban⁶, Jessica Oswald⁷, Matthew W. Swisher⁸, Ina Jazić⁹, Tiffany Healey⁹, Wendy Kampman⁹, Darin J. Correll⁹, Scott G. Weiner¹⁰

¹CenExel JBR Clinical Research, Salt Lake City, UT; ²ERG Clinical, Houston, TX; ³CenExel ACMR Clinical Research, Atlanta, GA; ⁴HD Research, LLC, Bellaire, TX; ⁵Arizona Research Center, Phoenix, AZ; ⁶OrthoNebraska, Omaha, NE; ⁷Departments of Emergency Medicine and Anesthesia, UC San Diego Health, San Diego, CA; ⁸UC San Diego Health, San Diego, CA; ⁹Vertex Pharmaceuticals, Boston, MA; ¹⁰Brigham and Women’s Hospital, Boston, MA

INTRODUCTION

Moderate-to-severe acute pain presents a significant management challenge due to the need to balance therapeutic efficacy and safety concerns within constraints of available treatments

While opioids are effective for pain relief, their use is limited by safety, tolerability, and addiction risks¹

Suzetrigine (SUZ) is a highly selective voltage-gated sodium channel 1.8 (Na_V1.8) inhibitor with no addiction potential based on its mechanism of action²

In two Phase 3 randomized, double-blind, placebo-controlled trials (RCTs)³:

SUZ demonstrated a statistically significant reduction in pain compared to placebo (primary endpoint)

Neither trial showed SUZ superiority over hydrocodone bitartrate/acetaminophen (HB/APAP), the most frequently prescribed opioid combination and dose (5/325 mg) in the conditions studied

The majority of adverse events (AEs) were mild to moderate in severity and there was a lower incidence of AEs observed in participants receiving SUZ than those receiving HB/APAP or placebo

There were fewer AEs of vomiting and/or nausea (common side effects of opioids) in participants receiving SUZ than those receiving HB/APAP

In a supportive Phase 3 single-arm safety and effectiveness (SASE) trial, most participants (83.2%) rated SUZ effectiveness for treating pain on a patient global assessment (PGA; secondary endpoint) as good, very good, or excellent⁴

In all three trials, SUZ was generally safe and well tolerated with no serious AEs related to SUZ^{3, 4}

SUZ is approved in the US to treat moderate-to-severe acute pain in adults

Here we report on opioid-free pain management with SUZ across these trials in moderate-to-severe acute pain conditions

MATERIAL AND METHODS

Two Phase 3 RCTs evaluating SUZ for 48 hours in participants with moderate-to-severe acute pain after abdominoplasty or bunionectomy were conducted (Figure 1)³

Participants were randomized 2:2:1 to SUZ, HB/APAP, or placebo

A Phase 3 SASE trial enrolled participants with moderate-to-severe acute pain following a scheduled surgical procedure (most common were orthopedic, plastic, and otorhinolaryngologic) or after presenting with moderate-to-severe acute pain of non-surgical origin (most common were sprains and strains of upper and lower extremities) (Figure 2)⁴

Opioid use was not allowed during treatment except for RCT participants who were randomized to receive HB/APAP

Opioid use was permitted if participants discontinued treatment prematurely

We analyzed opioid use in participants after early discontinuation of treatment in these three trials

RCT Designs

Phase 3 Randomized, Controlled Trials in Established Models of Acute Pain

Study Design

Suzetrigine tablets: 100-mg then 50-mg every 12 hours administered orally

HB/APAP capsules: 5-mg/325-mg every 6 hours administered orally

Rescue medication: ibuprofen was permitted, if needed, for pain relief. Opioids and other pain medicines were not allowed during treatment

Key Eligibility Criteria

Age: 18 to 80 years

Reported pain: moderate or severe on the VRS and ≥4 on the NPRS within 4 hours after abdominoplasty or 9 hours after removal of the popliteal sciatic nerve block (with ropivacaine) after a bunionectomy

SASE Trial Design

Phase 3 Single-arm Safety and Effectiveness Trial in a Broad Population of Surgical and Non-surgical Patients With Acute Pain in a Real World Setting

Study Design

Suzetrigine tablets: 100-mg first dose, then 50-mg every 12 hours administered orally for 14 days or until pain resolved

Rescue medication: ibuprofen and acetaminophen were permitted, if needed, for pain relief, in line with standard multimodal therapy. Opioids and other pain medications were not allowed during treatment

Key Eligibility Criteria

Age: 18 to 80 years

Reported pain: moderate or severe on the VRS and ≥4 on the NPRS following surgical procedures or after presenting to a medical facility with non-surgical pain of new origin (prior 48 hours; not related to a prior known condition)

RESULTS

Most Participants Receiving Suzetrigine Completed Treatment in the 48-hour RCTs With a Small Percentage Discontinuing Early

In Both RCTs, a Numerically Lower Proportion of Participants Receiving Suzetrigine Discontinued Treatment Early and Received Opioids Compared to Placebo; A Total of 9.6% (Abdominoplasty) and 11.7% (Bunionectomy) of RCT Participants Receiving Suzetrigine Discontinued Treatment Early and Received Opioids

Most Participants Completed Treatment With Suzetrigine in the SASE Trial With Only a Small Percentage Discontinuing Treatment Early; Only 1 (0.4%) SASE Participant Discontinued Treatment Early and Received Opioids

DISCUSSION

Current pain management practices strive for effective pain relief while minimizing side effects

The benefit/risk profile of SUZ in various moderate-to-severe acute pain conditions suggests opioid-free pain relief is possible with SUZ after surgical procedures and non-surgical conditions, which is beneficial even in the acute setting