Nonopioid Suzetrigine Demonstrates Positive Phase 3 Results for Acute Pain
Suzetrigine could represent the first new nonopioid drug in a distinct class of pain medications in approximately 20 years.
Suzetrigine, an investigational nonopioid pain therapy for acute pain management, demonstrated positive phase 3 clinical trial results at ANESTHESIOLOGY 2024, the annual meeting of the American Society of Anesthesiologists, taking place from October 18 to 22 in Philadelphia, Pennsylvania.1 Data presented at the meeting showcased the drug’s efficacy and safety across various pain conditions and settings.
Man in lower back pain / SasinParaksa - stock.adobe.com
Voltage-gated sodium channel 1.8 is (NaV1.8) has emerged as a potential therapeutic target for treating moderate-to-severe acute pain. This channel is selectively expressed in peripheral nociceptors and dorsal root ganglia, making it a key player in pain signaling.
Suzetrigine, a novel oral medication, is a potent and highly selective inhibitor of NaV1.8 with no potential for misuse. Its unique properties position it to address the unmet need for effective pain management options beyond opioids and current nonopioid treatments.
Suzetrigine’s phase 3 program consisted of 3 studies: two randomized, double-blind, placebo-controlled trials and one single-arm safety and efficacy study. Whereas the first 2 trials evaluated suzetrigine following abdominoplasty and bunionectomy surgeries, respectively, the third study enrolled patients with a diverse range of surgical and non-surgical pain conditions to assess suzetrigine’s safety and efficacy in various settings.
Data from the trials was presented in 2 poster abstracts.
The first poster presented the results of the abdominoplasty and bunionectomy trials. In these randomized, double-blind, placebo-controlled trials, 1118 participants underwent abdominoplasty, and 1073 participants underwent bunionectomy. All participants were aged between 18 and 80 years.2
Participants who rated 4 or higher on the numeric pain rating scale (NPRS) following surgery were randomized in a 2:2:1 ratio to receive either suzetrigine, hydrocodone bitartrate/acetaminophen (HB/APAP), or a placebo.
The primary endpoint was the time-weighted sum of the pain intensity difference (SPID48) calculated from NPRS scores over 48 hours. A higher SPID48 value indicated a greater reduction in pain compared to the baseline level.
Key secondary endpoints included the SPID48 for suzetrigine compared to HB/APAP, and the time required for suzetrigine to achieve a 2-point or greater reduction in NPRS compared to placebo. Safety was also evaluated as a secondary endpoint.
Suzetrigine treatment significantly reduced pain compared to placebo. In the abdominoplasty trial, the least squares (LS) mean difference in SPID48 between suzetrigine and placebo was 48.4% (95% CI: 33.6, 63.1; P < .001). In the bunionectomy trial, the LS mean difference was 29.3% (95% CI: 14.0, 44.6; P = .0002).
Neither trial demonstrated that suzetrigine was superior to HB/APAP in terms of SPID48. However, suzetrigine did exhibit a more rapid onset of meaningful pain relief than placebo in both trials. The median time to achieve a 2-point or greater reduction in NPRS from baseline was significantly shorter with suzetrigine (119 minutes in the abdominoplasty trial and 240 minutes in the bunionectomy trial) compared to placebo (480 minutes in both trials; P < .001 and P = .0016, respectively).
Suzetrigine was generally safe and well-tolerated in both trials, with adverse events (AEs) consistent with the post-surgical settings. The overall incidence of AEs was lower with suzetrigine compared to placebo or HB/APAP. Following abdominoplasty, the incidence of participants with any AEs was 50.0% with suzetrigine, 56.3% with placebo, and 60.7% with HB/APAP. Following bunionectomy, the rates were 31.0%, 35.2%, and 41.8%, respectively. No serious AEs were related to suzetrigine.
READ MORE: Acupuncture Represents Effective Nonpharmacologic Treatment for Sciatica Pain Management
To expand upon the results of the first 2 trials, investigators conducted a third study to evaluate the safety and efficacy of suzetrigine for moderate-to-severe acute pain in a broader patient population. This included both postoperative surgical patients and non-surgical patients with painful medical conditions.3 Results of this study were presented in a second poster.
The phase 3, single-arm study enrolled adults aged 18 to 80 with pain rated 4 or higher on the NPRS following surgery or presenting to a medical facility with newly developed moderate-to-severe acute pain within the past 48 hours. Participants received suzetrigine for 14 days or until pain resolved.
The primary objective was to assess safety, while the secondary objective was to evaluate suzetrigine’s effectiveness in treating acute pain at the end of treatment as assessed by a patient global assessment.
A total of 256 participants (222 surgical, 34 non-surgical) received suzetrigine. The most common surgical procedures were orthopedic, plastic and otorhinolaryngologic. The most common non-surgical conditions were sprains and strains of the upper and lower extremities.
Suzetrigine was generally safe and well-tolerated in both surgical and non-surgical patients. Most AEs were mild or moderate in severity, with headache being the most common, occurring in 7% of participants. No serious AEs were related to suzetrigine.
Most participants (83.2%) rated the effectiveness of suzetrigine for treating pain as good, very good, or excellent at the end of treatment.
Poster presentations at ASA marked the first public disclosure of positive phase 3 clinical trial results for suzetrigine since developer Vertex Pharmaceuticals’ January 2024 announcement of trial success. Overall, the data demonstrated suzetrigine’s potential as a safe and effective nonopioid treatment for various types of moderate-to-severe acute pain.
Importantly, suzetrigine could represent the first new nonopioid treatment in a distinct class of pain medications in approximately 20 years.
“Our goal in developing suzetrigine is to deliver the first nonopioid acute pain treatment in more than 2 decades and to change the paradigm of pain management as we know it,” said Carmen Bozic, MD, executive vice president of global medicines development and medical affairs, and chief medical officer at developer Vertex Pharmaceuticals, in a news release preceding the conference.1
“For decades, pain treatment options have been extremely limited,” said Todd Bertoch, MD, a practicing anesthesiologist and researcher, CEO of CenExel JBR Clinical Research in Salt Lake City, and lead presenter for the suzetrigine phase 3 data, in the same release.1 “This research has brought about a renewed optimism for the future of pain management, and I’m looking forward to sharing our findings with the ASA community. Suzetrigine offers the potential to fill the critically important treatment gap between opioids and other currently available therapies that have either limited efficacy and/or poor tolerability.”
In July 2024, the FDA accepted Vertex Pharmaceuticals' New Drug Application for suzetrigine. The drug has a Prescription Drug User Fee Act date of January 30, 2025.4
READ MORE: Nonopioid Pain Management Resource Center
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