In 2 pivotal phase 3 randomized clinical trials, the investigational selective NaVThe 1,8-blocker was associated with a statistically significant improvement in pain intensity and a clinically significant reduction in moderate-to-severe acute postoperative pain compared with placebo, biotech company Vertex said in a statement on Tuesday.
After abdominoplasty or pneumonectomy, treatment with VX-548 resulted in a statistically significant improvement in the primary study endpoint—time-weighted sum of pain intensity difference from 0 to 48 hours (SPID48) compared with placebo as well as a clinically significant reduction in pain from baseline at 48 hours as measured by the Numerical Pain Rating Scale (NPRS). In the phase 3 safety and efficacy study, VX-548 was effective and well tolerated in a wide range of other surgical and nonsurgical acute pain conditions.
“VX-548’s benefit-risk profile positions it ideally to potentially fill the gap between drugs with good tolerance but limited efficacy and opioid drugs with therapeutic efficacy but known risks, including the potential for addiction,” Reshma Kewalramani, MD, CEO and chairman. of Vertex, the company’s announcement states.
Vertex plans to submit a New Drug Application to the US Food and Drug Administration by mid-2024, according to the company.
Phase 3 Program
Adult patients aged 18 to 80 years undergoing abdominoplasty (n = 1118) and pneumonectomy (n = 1073) received either VX-548 (initial dose 100 mg followed by 50 mg every 12 hours), hydrocodone/acetaminophen ([HB/APAP] 5 mg/325 mg orally every 6 hours over a 42-hour period) or placebo after surgery.
Primary. Meeting the primary endpoint, SPID48 with VX-548 was found to be superior to placebo in both studies, according to the news release. After abdominoplasty, the least square [LS] The mean difference in SPID48 between VX-548 and placebo was 48.4 (95% CI, 33.6 to 63.1; Pi <.001). After bunionectomy surgery, the LS mean difference in SPID48 between VX-548 and placebo was 29.3 (95% CI, 14.0 to 44.6; Pi = .0002).
Secondary key. The first key secondary endpoint tested the hypothesis that VX-548 was superior to hydrocodone/acetaminophen (HB/APAP) in SPID48 after both surgeries and was not met, according to the release. After abdominoplasty, the mean LS difference between VX-548 and HB/APAP was 6.6 (95% CI, -5.4 to 18.7; Pi = 0.278) and after pneumonectomy, -20.2 (95% CI, -32.7 to -7.7; Pi = .002).
However, time to substantial pain relief (≥2-point reduction in NPRS), the second key secondary endpoint in both trials, also favored VX-548, Vertex said. Median time to endpoint was 2 hours for abdominoplasty (nominal Pi <. 001) and 4 hours for pneumonectomy (nominal Pi < 0.002) compared to 8 hours for placebo in both studies.
The other secondary endpoints were consistent with the primary outcome, the manufacturer said.
In the single-arm phase 3 safety study, the most common adverse events were categorized as mild to moderate, and no serious adverse events related to the study drug were reported during oral treatment with VX-548. For patients receiving VX-548, the incidence of adverse events was lower compared to placebo (post-abdominoplasty 50.0% vs 56.3%, respectively, post-pneumonectomy 31.0% vs 35.2% , respectively). Efficacy was determined using a Patient Global Assessment (PGA) at the end of the study period. Most (83.2%) patients rated VX-548 as “good, very good, or excellent” in treating pain.
“As a physician who has treated patients suffering from pain for many years, I know firsthand the critical need for new, effective and safe treatment options,” Jessica Oswald, MD, MPH, associate physician in emergency medicine and pain management at the University of California San. Diego, and a member of the Vertex Pain Acid Steering Committee, said in the Vertex statement. “The Phase 3 safety and efficacy in the three studies are impressive and demonstrate the potential of VX-548 to change the paradigm of pain management. I look forward to having a new class of acute pain medication – the first in more than two decades – used as an alternative to opioids to help the millions of people affected by acute pain.”
