Acetaminophen/Hydrocodone Bitartrate

iStock, hapabapa BMO Capital Markets analyst Evan Seigerman in a note to investors said the late-stage data for Vertex’s experimental non-opioid pain medication “reaffirms our confidence in the strength of suzetrigine’s profile.” However, William Blair analysts view these data as “an incremental positive” as the company faces challenges in targeting the acute pain market. Vertex Pharmaceuticals ’ investigational non-opioid pain therapy suzetrigine has a cleaner safety profile than standard pain relief medicines and even placebo, according to full Phase III data presented over the weekend at the 2024 annual meeting of the American Society of Anesthesiologists in Philadelphia. In study participants who were undergoing abdominoplasty—more commonly known as a tummy tuck—adverse events of any severity arose in 50% of patients given suzetrigine. By comparison, toxicities were detected in 60.7% of patients managed with hydrocodone bitartrate/acetaminophen (HB/APAP) and in 56.3% of placebo comparators. Suzetrigine continued to have a better safety pro HB/APAP and placebo even after disaggregating according to severity. Severe toxicities developed in 1.8% of abdominoplasty patients in the suzetrigine arm, versus 2% and 2.7% in HB/APAP and placebo counterparts, respectively. One patient in the placebo arm died. Similar safety findings were observed in patients who underwent bunionectomy, which is a surgical procedure to correct a bone deformity in the toes. Aside from the positive safety data, Vertex also reported an efficacy update for suzetrigine at ASA 2024. In abdominoplasty patients, suzetrigine monotherapy led to a 48.4-point improvement in pain scores, as measured by 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 less than 0.0001, according to Vertex’s presentation. While suzetrigine’s effect seems to be weaker in bunionectomy patients, it still remained significantly better than placebo. Mean SPID48 scores were 29.3 points higher after suzetrigine treatment versus placebo. Compared with the HB/APAP combo, however, suzetrigine monotherapy did not lead to significantly better pain relief. Mean SPID48 scores improved by only 6.6 points in abdominoplasty patients versus HB/APAP, an effect that fell short of significance. Meanwhile, in bunionectomy patients, mean SPID48 scores appear to have worsened by 20.2 points in the suzetrigine arm, which was statistically significant. Suzetrigine is an orally available pain signal inhibitor that works by targeting and binding to the NaV1.8 voltage-gated sodium channel. Typically found on pain-sensing neurons, 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 suzetrigine for moderate to severe acute pain, with a target action date on Jan. 30, 2025 . If approved, suzetrigine could provide patients with an effective non-opioid option for pain relief. BMO Capital Markets analyst Evan Seigerman in a note to investors said the detailed late-stage data for Vertex’s non-opioid pain medication “reaffirms our confidence in the strength of suzetrigine’s pro acute pain.” However, William Blair analysts in a note to investors said they view Vertex’s presentation at ASA 2024 as “an incremental positive” for suzetrigine with some challenges as the company targets the acute pain market. “In the post-surgical outpatient setting, we continue to believe suzetrigine has a strong argument for inclusion in the market but note that pricing remains a point of investor contention along with how this impacts reimbursement, formulary placement, and prior authorization requirements, the latter of which Vertex is keen to avoid,” the analysts wrote. Truist Securities analyst Joon Lee in a note said his firm is “not entirely sold yet on the commercial case for suzetrigine in acute pain,” adding that “if there is indeed will to use non-opioid analgesic, we think there are numerous options that are readily available that will be significantly cheaper than suzetrigine.”

Vertex detailed Phase 3 data for its non-opioid treatment that could mark a drastic shift in pain management . The company expanded on its interim readout on Sunday at the American Society of Anesthesiologists’ annual meeting. Back in January, Vertex said suzetrigine was statistically significant at improving pain symptoms compared to placebo following tummy tuck procedures and bunion removal surgery. The full data show the drug was more pronounced in patients who had the tummy tuck procedure, with suzetrigine demonstrating a 48.4 mean improvement in pain compared to placebo as measured by a scale of post-operative pain symptoms after anesthesia wears off. Following bunion removal surgery, suzetrigine had a 29.3 mean difference from placebo on the same scale. Lead investigator Todd Bertoch zeroed in on the number of adverse events that occurred post-treatment. “This is the first study I’ve ever done where the investigational product had fewer adverse events than placebo,” he told Endpoints News . “I think that’s pretty remarkable.” Half of the patients that were given suzetrigine had an adverse event after being treated after a tummy tuck, compared to 56.3% of patients given placebo and 60.7% given Vicodin. After bunion removal surgery, 31% of suzetrigine-treated patients had an adverse event versus 35.2% for placebo and 41.8% for Vicodin. There were no serious adverse events related to the drug, the new data showed. Despite beating placebo and turning heads on safety, suzetrigine did not display a statistically significant improvement in pain reduction compared to Vicodin, a secondary endpoint in the trial. Bertoch, who has been a paid consultant for Vertex but does not work for the company, said the data still show a drug that could fill a gap in pain management. “It looks like this drug is effective and you can put it in this place between where you need opioids and you have a safety profile that’s so much better,” he said. The company also shared expanded single-arm data on Saturday. Those data similarly showed the drug was safe and had positive effectiveness ratings from patients. That trial included postoperative surgical patients and those who presented at a medical facility with moderate or severe acute pain that was new. There were no serious adverse events related to the drug, and 83.2% of trial participants said the effectiveness of suzetrigine at treating pain was good, very good, or excellent. The three trials form the basis for Vertex’s approval application, which was accepted by the FDA in July with a decision set for the end of January 2025. In the meantime, studies expanding suzetrigine into neuropathic pain conditions are progressing. A Phase 2 study testing the treatment in patients with painful lumbosacral radiculopathy is still on track for a readout before the end of the year. Bertoch wouldn’t elaborate on how the data look, given that his clinical research organization is included in the study, but he expressed optimism. “I don’t see a reason why that success should not translate into chronic pain,” he said.