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FDA Approves Vertex Pharmaceuticals' Suzetrigine for Acute Pain Management
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Key Takeaways
- Suzetrigine, a NaV1.8 inhibitor, is the first new non-opioid analgesic class for acute pain in over 20 years, approved by the FDA.
- Clinical trials showed significant pain reduction with suzetrigine compared to placebo in abdominoplasty and bunionectomy surgeries.
Suzetrigine, a selective inhibitor of the NaV1.8 sodium channel, offers an alternative opioid treatment option for patients to treat moderate to severe pain without risk of addiction.
According to a new announcement, the FDA has approved suzetrigine (Vertex Pharmaceuticals), an oral selective NaV1.8 pain signal inhibitor, to treat patients who experience moderate-to-severe acute pain. Marketed as Journavx, the novel, non-opioid therapy becomes the first new class of medicine to treat acute pain in over 20 years.1
The new drug application (NDA) for suzetrigine, formally known as VX-548, was based on data from a phase 3 program that included 2 randomized, double-blind, placebo-controlled trials; 1 post abdominoplasty surgery and 1 post bunionectomy surgery. The program also included a single arm safety and efficacy study that included patients with a wide range of surgical and non-surgical pain conditions.2
Suzetrigine, which previously received breakthrough therapy, fast track, and priority review designations by the FDA, is contraindicated for concomitant use with strong CYP3A inhibitors. Additionally, patients should avoid food or drink containing grapefruit when taking the medication.
"Today’s approval is an important public health milestone in acute pain management," Jacqueline Corrigan-Curay, JD, MD, acting director of the FDA's Center for Drug Evaluation and Research, said in a statement.1 "A new non-opioid analgesic therapeutic class for acute pain offers an opportunity to mitigate certain risks associated with using an opioid for pain and provides patients with another treatment option. This action and the agency’s designations to expedite the drug’s development and review underscore FDA’s commitment to approving safe and effective alternatives to opioids for pain management."
In the pivotal studies, suzetrigine met its primary end point of the time-weighted sum of the pain intensity difference from 0 to 48 hours, and demonstrated a clinically meaningful reduction in pain from baseline at 48 hours on the Numeric Pain Rating Scale (NPRS) after both abdominoplasty and bunionectomy surgeries. Compared with placebo, the mean difference in pain intensity from 0 to 48 hours for abdominoplasty was 48.4, and 29.3 for bunionectomy, showcasing a statistically significant improvement.3 Among the patients in the single arm safety and efficacy study, 83.2% rated suzetrigine as good, very good, or excellent in treating pain based on the Patient Global Assessment (PGA) scale.
All 3 studies revealed that suzetrigine was safe and well tolerated by participants, with majority of adverse events (AEs) being reported as mild-to-moderate. Findings from the 2 randomized controlled trials demonstrated that following abdominoplasty, 50% of patients who received suzetrigine experienced AEs, compared with 56.3% in the placebo group. After bunionectomy, 31% of patients who received the therapy reported adverse events, compared with 35.2% in the placebo group. Overall, the most common AEs observed in study participants on suzetrigine were itching, muscle spasms, increased blood level of creatine phosphokinase, and rash.
An poster presented at ANESTHESIOLOGY 2024, the annual meeting of the American Society of Anesthesiologists, held October 18-22 in Philadelphia, Pennsylvania, demonstrated suzetrigine's positive effect across phase 3 clinical trial abdominoplasty and bunionectomy trials, underscoring the drug’s efficacy and safety across various pain conditions and settings. In these trials, 1118 participants underwent abdominoplasty, and 1073 participants underwent bunionectomy. All participants were aged between 18 and 80 years.4
Participants who rated 4 or higher on the 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 end point 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 with baseline. Key secondary end points included the SPID48 for suzetrigine compared with HB/APAP, and the time required for suzetrigine to achieve a 2-point or greater reduction in NPRS compared to placebo. Safety was also assessed as a secondary end point.
Results showed that suzetrigine treatment significantly reduced pain compared with 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. Additional findings demonstrated that 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 with placebo (480 minutes in both trials; P < .001 and P = .0016, respectively).
Suzetrigine was generally safe and well-tolerated in both trials, with AEs consistent with the post-surgical settings. The overall incidence of AEs was lower with suzetrigine compared with 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 adverse events were related to suzetrigine.
In another poster presented at ANESTHESIOLOGY 2024, investigators conducted a phase 3, single-arm study to assess the safety and efficacy of suzetrigine for moderate-to-severe acute pain in a broader patient population.5 This patient population included both postoperative surgical patients and non-surgical patients with painful medical conditions. The 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 and the secondary objective was to investigate the efficacy of suzetrigine 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.
Overall, in this second presented poster, suzetrigine was generally safe and well-tolerated in both surgical and non-surgical patients. Most AEs were reported as mild or moderate in severity, with headache being reported as the most common, occurring in 7% of participants. No serious AEs were related to suzetrigine, as noted by researchers. Majority of participants (83.2%) rated the efficacy of suzetrigine for treating pain as good, very good, or excellent at the end of the treatment period.
In a prior study published in The New England Journal of Medicine, researchers observed that suzetrigine reduced acute pain over a 48-hour period after abdominoplasty or bunionectomy with mild-to-moderate AEs at the highest dose. This previous trial was performed as 2 phase 2, randomized, double-blind, placebo-controlled studies. Participants included were aged between 18 years and 75 years with a pain score of at least 4 on the NPRS. Pain was also rated as moderate or severe on the Verbal Categorical Rating Scale in 4 hours after completion of the surgery and general anesthesia for those who underwent abdominoplasty and in 9 hours after removal of popliteal sciatic nerve block on postoperative day 1 in the bunionectomy trial.6
For the abdominoplasty trial, 303 patients were included, with 81.5% who completed the treatment period. In the bunionectomy trial, 274 patients were included and 90.1% completed the treatment. The least-squares mean difference for the high-dose group and placebo group was 37.8 for participants in the abdominoplasty trial and 36.8 in the bunionectomy trial. For both studies, patients who received the lower doses displayed similar results as the placebo. Overall, investigators reported that headache and constipation were the most common adverse events reported with suzetrigine in this study.
