Non-Opioid Pain Pill for Acute Pain Relief Approved

Suzetrigine Offers a Novel Alternative to Opioids but Raises Questions About Efficacy

Topline

The FDA has approved suzetrigine (Journavx), the first non-opioid analgesic of its kind, for treating moderate to severe acute pain in adults. The drug, developed by Vertex Pharmaceuticals, is a highly selective NaV1.8 sodium channel blocker, targeting peripheral pain neurons without acting on the brain, making it a non-addictive alternative to opioids. However, clinical trials show that while it is effective, it does not outperform opioid-based treatments.

Study Details

Suzetrigine represents the first new drug class for acute pain management in more than two decades. Unlike opioids, which affect the central nervous system, suzetrigine selectively inhibits NaV1.8, a voltage-gated sodium channel found in peripheral pain-sensing neurons. This reduces pain transmission without the risk of opioid dependence.

The approval was based on two Phase III randomized controlled trials, evaluating suzetrigine’s efficacy in:

• Abdominoplasty (tummy tuck) patients

• Bunionectomy (foot surgery) patients

Both studies compared suzetrigine with hydrocodone-acetaminophen (opioid-based pain relief) and placebo.

Methodology

• Study Population:

  • 874 patients undergoing abdominoplasty or bunionectomy

  • Additional safety data from a single-arm study (256 participants) with various acute pain conditions

• Treatment Groups:

  • Suzetrigine 50 mg

  • Hydrocodone-acetaminophen

  • Placebo

• Primary Endpoint:

  • Pain intensity reduction (measured by the numeric pain rating scale over 48 hours)

• Secondary Outcomes:

  • Speed of pain relief

  • Safety and side effects

Key Findings

• Pain Reduction:

  • Suzetrigine significantly reduced pain compared to placebo.

  • The mean pain score improvement was 48.4 points (P<0.0001) after abdominoplasty and 29.3 points (P=0.0002) after bunionectomy.

  • However, suzetrigine was no better than hydrocodone-acetaminophen in pain relief.

• Time to Pain Relief:

  • Suzetrigine provided faster relief than placebo, but its effects took longer to set in compared to opioids:

    • Suzetrigine: 119 min (abdominoplasty) / 240 min (bunionectomy)

    • Placebo: 480 min for both surgeries

    • Opioids: Faster pain relief than suzetrigine

• Safety Profile:

  • Common side effects: Itching, muscle spasms, increased creatine phosphokinase levels, and rash.

  • Contraindications:

    • Avoid use with CYP3A inhibitors (e.g., some antibiotics, antifungals).

    • Patients should avoid grapefruit (alters drug metabolism).

    • Liver impairment increases side effect risks.

    • May reduce effectiveness of hormonal birth control.

Implications for Practice

1. A Non-Opioid Option with Some Limitations

   • Suzetrigine offers a safer alternative to opioids, but its effectiveness is comparable to existing opioid-based pain relievers.

   • Patients may still need additional pain management strategies, especially for severe post-surgical pain.

2. Safer for Patients at Risk of Opioid Addiction

   • Ideal for patients with opioid use disorder risk or those seeking non-addictive pain relief options.

   • However, long-term safety data is still limited.

3. Further Research Needed

   • Vertex is investigating suzetrigine in sciatica and diabetic peripheral neuropathy.

   • Future studies should assess long-term pain relief, real-world patient outcomes, and broader applications.