VX-548 Significantly Reduces Moderate to Severe Acute Pain, Phase III Program Data Reveal

Credit: Adobe Stock/Pitchayaarch

Positive results from a phase III program evaluating the selective NaV1.8 inhibitor, VX-548, demonstrated significant improvements in pain intensity and pain reduction compared with placebo.¹ The trials proved favorable safety, tolerability, and efficacy in patients with moderate to severe post-surgical pain.

“The VX-548 benefit-risk profile ideally positions it to potentially fill the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential,” Reshma Kewalramani, MD, chief executive officer and president of Vertex, said in a statement.¹

The program included 2 randomized, double-blind, placebo-controlled, pivotal trials, one of which focused on the safety and efficacy of VX-548 for the treatment of acute pain post-abdominoplasty surgery and one following bunionectomy surgery, as well as a single arm safety and efficacy study which recruited patients with a vast range of surgical and non-surgical pain conditions. Adult patients (n = 1118) received either VX-548 (initial dose of 100 mg followed by 50 mg every 12 hours), hydrocodone bitartrate/acetaminophen ([HB/APAP] 5 mg/325 mg orally ever 6 hours over a period of 42 hours), or placebo.

The primary endpoint was the time-weighted sum of the pain intensity difference between 0 and 48 hours using the Sum of Pain Intensity Difference score (SPID48) compared with placebo, in addition to a clinically meaningful reduction in pain from baseline at 48 hours using the Numeric Pain Rating Scale (NPRS). Results indicated reductions in pain in both studies (abdominoplasty: least square [LS] mean difference in SPID48 between VX-548 and placebo: 48.4 [95% confidence interval (CI): 33.6, 63.1; P <.0001]; bunionectomy: LS mean difference in SPID48 between VX-548 and placebo: 29.3 [95% CI: 14.0, 44.6; P = .0002]).

The key secondary endpoint, superiority to HB/APAP on SPID48 post-surgery, was not achieved (abdominoplasty: LS mean difference between VX-548 and HB/APAP: 6.6 [95% CI: -5.4, 18.7; P = .2781]; bunionectomy: LS mean difference between VX-548 and HB/APAP = -20.2 [95% CI: -32.7, -7.7; P = .0016]).

However, VX-548 demonstrated a more rapid onset to meaningful pain relief, defined as a ≥2-point reduction in NPRS, when compared with placebo in both post-surgery trials. The median time to significant pain relief was 8 hours in the placebo cohort compared with 2 hours for patients receiving VX-548 in the abdominoplasty study and 4 hours in the bunionectomy study.

The other secondary endpoints, such as safety and tolerability, were consistent with the primary outcome. The most common adverse events were categorized as mild to moderate, and no serious adverse events related to the study drug were reported. For patients receiving VX-548, the incidence of adverse events was lower when compared with placebo (post-abdominoplasty: 50.0% vs 56.3%, respectively; post-bunionectomy: 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 treating patients suffering from pain for many years, I know firsthand the critical need for new, efficacious and safe treatment options,” Jessica Oswald, MD, MPH, associate physician in Emergency Medicine and Pain Medicine, University of California San Diego, and Vertex Acute Pain Steering Committee member, said in a statement.¹ “The Phase 3 safety and efficacy across the three studies are impressive and demonstrate VX-548’s potential to change the paradigm of pain management. I look forward to the potential of having a new class of acute pain medicine — the first in more than two decades — to use as an alternative to opioids to help the millions of people impacted by acute pain.”

References

1. ^{Vertex announces positive results from phase 2 study of VX-548 for the treatment of painful diabetic peripheral neuropathy. Vertex Pharmaceuticals. December 13, 2023. Accessed January 30, 2024. https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-positive-results-phase-2-study-vx-548-treatment.}