Clinically Significant Pain Relief with a Non-Opioid Drug

Positive phase 3 study results with investigational oral, non-opioid VX-548 for acute pain

VX-548 recently completed phase 3 clinical trials for treating moderate to severe pain.¹ VX-548 is an oral, non-opioid agent that selectively inhibits NaV1.8, a voltage-gated sodium channel. The voltage-gated sodium channel is critically involved in peripheral nervous system pain signaling. During phase 2 clinical trials in patients treated for abdominoplasty and bunionectomy surgeries, as well as in patients with painful diabetic peripheral neuropathy, VX-548 was well tolerated. The phase 3 clinical trials included more than 2,000 post-surgical patients from 18 to 80 years old, and an additional safety and effectiveness study (n=256) in patients with different non-surgical and surgical conditions who were followed for up to 14 days.

The randomized post-surgical patients who received VX-548 received an initial dose of 100 mg, followed by 50 mg every 12 hours for three doses. Comparative agents were hydrocodone bitartrate/acetaminophen (5 mg/325 mg), given every six hours over 42 hours, or placebo.

Treatment with VX-548 led to statistically significant improvements in the patients who were post-abdominoplasty or post-bunionectomy surgery for the primary end point of the time-weighted sum of the pain intensity difference from 0 to 48 hours compared with patients who received placebo, as well as a clinically meaningful reduction in pain from baseline at 48 hours on the Numeric Pain Rating Scale [NPRS] (abdominoplasty: 95% confidence interval [CI]: 33.6, 63.1; P<0.0001; bunionectomy: 95% CI: 14.0, 44.6; P=0.0002).

A key secondary end point tested was that VX-548 would be superior to hydrocodone bitartrate/acetaminophen on SPID48 (i.e., the time-weighted sum of the pain intensity difference from 0 to 48 hours) following either bunionectomy surgery or abdominoplasty surgery. This secondary end point was not met in either post-surgical trial.

Time to meaningful pain relief was another secondary end point in both post-surgical trials and was defined as at least a two-point reduction in NPRS score from baseline compared with placebo. For this end point, patients who received VX-548 had more rapid onset of pain relief than patients who received placebo in both post-surgical trials. The median time to meaningful pain relief with placebo was eight hours in both studies; the median time to meaningful pain relief with VX-548 was two hours in post-abdominoplasty patients, and the median time to meaningful pain relief with VX-548 was four hours in the post-bunionectomy patients.

In the phase 3, single-arm safety and effectiveness study, patients treated with VX-548 received 100 mg for one dose followed by 50 mg every 12 hours and were evaluated for up to 14 days. These patients had a wide range of other surgical and non-surgical acute pain circumstances. These patients tolerated VX-548 well and had positive safety results. Effectiveness was measured by a Patient Global Assessment. At the end of treatment with VX-548, 83.2% of patients evaluated it as good, very good or excellent for the treatment of their pain.

Most adverse events were mild to moderate, with no serious adverse events related to VX-548 treatment. In the two randomized controlled trials in the post-surgical patients, the adverse event incidence was lower in patients who received treatment with VX-548 than in those who received placebo (following abdominoplasty: 50% [VX-548] vs. 56.3% [placebo]; and following bunionectomy: 31% [VX-548] vs. 35.2% [placebo]).

Statistically significant improvements in pain management were attained with VX-548 treatment compared with placebo. Also, clinically meaningful pain management reduction, as noted from baseline in both post-surgical treated, randomized controlled trials, was attained with VX-548. VX-548 was safe and well tolerated in the treatment of patients with a range of surgical and non-surgical pain conditions for up to 14 days.

VX-548 is currently in phase 2 clinical trials for treating painful diabetic peripheral neuropathy, as well as for treating patients with painful lumbosacral radiculopathy. The manufacturer plans to submit a New Drug Application for VX-548 for treating moderate to severe pain in mid-2024.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

Reference

1.     Vertex announces positive results from the VX-548 phase 3 program for the treatment of moderate-to-severe acute pain (press release). 2024 Jan 30.