Vertex PharmaceuticalsInvestigational non-opioid pain treatment suzetrigin has a cleaner safety profile than standard pain medications and even placebo, according to full Phase III data presented over the weekend at the American Society of Anesthesiologists’ 2024 annual meeting in Philadelphia.
In study participants undergoing abdominoplasty – more commonly known as abdominoplasty – side effects of any severity occurred in 50% of patients receiving suzetrigin. In comparison, toxicities were detected in 60.7% of patients treated with hydrocodone bitartrate/acetaminophen (HB/APAP) and in 56.3% of placebo comparators.
Suzetrigine continued to have a better safety profile than HB/APAP and placebo even after stratification by severity. Serious toxicities developed in 1.8% of abdominoplasty patients in the suzetrigin arm, versus 2% and 2.7% in the HB/APAP and placebo arms, respectively. One patient in the placebo arm died.
Similar safety findings were seen in patients who underwent a bunionectomy, which is a surgical procedure to correct a bony deformity in the toes.
In addition to the positive safety data, Vertex also reported an efficacy update for suzetrigin at ASA 2024. In abdominoplasty patients, suzetrigin monotherapy led to a 48.4-point improvement in pain scores as measured by the SPID48, a tool that measures time-weighted pain intensity from 0 to 48 hours after surgery. This effect was statistically significant, with a p-value of less than 0.0001, according to Vertex’s presentation.
While the effect of suzetrigin appeared to be weaker in pneumonectomy patients, it remained significantly better than placebo. Mean SPID48 scores were 29.3 points higher after suzetrigin treatment versus placebo.
However, compared with the HB/APAP combination, suzetrigin monotherapy did not result in significantly better pain relief. Mean SPID48 scores improved by only 6.6 points in patients with abdominoplasty versus HB/APAP, an effect that was not significant. Meanwhile, in patients with pneumonectomy, mean SPID48 scores appeared to have worsened by 20.2 points in the suzetrigin arm, which was statistically significant.
Suzetrigine is an orally available blocker of the pain signal that works by targeting and blocking the NaV1.8 gated sodium channel. Typically found on neurons that detect pain, these channels help transmit pain signals from the peripheral nervous system back to the spine and brain. NaV1.8 channels are validated pain targets.
In July 2024, the FDA accepted Vertex’s new drug application for suzetrigin for moderate to severe acute pain, with Target action date 30 January 2025. If approved, suzetrigin could offer patients an effective non-opioid option for pain relief.
BMO Capital Markets analyst Evan Seigerman said in a note to investors that the detailed late-stage data for Vertex’s non-opioid pain reliever “confirms our confidence in the strength of suzetrigin’s profile in acute pain.”
But William Blair analysts in a note to investors said they see Vertex’s ASA 2024 presentation as “an incremental positive” for suzetrigin with some challenges as the company targets the acute pain market.
“In the post-surgical outpatient setting, we continue to believe that suzetrigin has a strong case for inclusion in the market, but note that pricing remains a point of investor contention along with how this affects reimbursement, formulation placement and prior approval requirements. which Vertex wants to avoid,” the analysts wrote.
Truist Securities analyst Joon Lee said in a note that his company is “not yet fully sold on the suzetrigin commercial case in acute pain,” adding that “if there is indeed a will to use a non-opioid analgesic, we believe there are many options that are readily available that will be significantly cheaper than suzetrigin.”
