Opioid pain relievers are highly addictive, contributing to high rates of opioid use disorder and overdose. According to the World Health Organization, opioid use is responsible for more than 70 percent of the deaths worldwide attributable to drug use. Amid soaring rates of opioid use and overdose, an effective non-opioid solution for treating pain would represent a significant medical breakthrough. An experimental non-opioid pain drug from Boston-based Vertex Pharmaceuticals has shown promise, demonstrated by two proof-of-concept Phase II clinical trials. The pair of trials evaluated the drug’s performance in treating acute post-surgical pain.
The current drug candidate, known as VX-548, performed better than placebo among study participants recovering from surgery to remove either bunions (bunionectomy) or excess abdominal fat (abdominoplasty).
The bunionectomy trial enrolled 274 people. They were randomly selected to receive VX-548 at one of three doses, a placebo, or an approved drug containing the opioid hydrocodone for post-surgical pain. The abdominoplasty trial enrolled 303 patients, who were randomly assigned to receive VX-548 at one of two doses, a placebo, or an opioid-based drug for post-surgical pain. Patients in both trials periodically rated their pain using the Sum of Pain Intensity Difference over 48 hours, and researchers calculated changes in pain levels over the same period.
Participants in both studies who received the highest dose of VX-548 saw significantly greater pain reductions than those receiving a placebo. The researchers did not find the same degree of benefit for patients receiving lower doses of the drug. The high-dose groups also showed greater benefits over a placebo than did the groups that received the opioid drugs in both studies. However, there were not enough participants to compare the effectiveness of the two treatments. Neither trial revealed any serious side events from taking VX-548.
VX-548 was developed to target a voltage-gated sodium channel, known as Nav1.8, that plays an important role in pain signaling in the peripheral nervous system. Researchers originally identified the channel’s potential as a target for relieving acute pain based on findings that people with genetic mutations that make Nav1.8 hyperactive can experience pain without an apparent cause.
One challenge in developing the drug was the similarity between Nav1.8 and other sodium channels that regulate heart, muscles, and brain functions. Therefore, VX-548 was developed to act on its target very specifically and avoid disrupting other channels.
Following the encouraging Phase II results, Vertex announced plans to advance VX-548 to Phase III trials for acute pain and to begin a Phase II dose-ranging study for the treatment of neuropathic pain. In addition, the Food and Drug Administration (FDA) has given VX-548 Breakthrough Therapy Designation for the treatment of moderate-to-severe acute pain.
“We are very pleased to complete our discussions with the FDA and reach agreement on the design of the pivotal development program for acute pain,” said Carmen Bozic, Chief Medical Officer at Vertex, in a press release. “VX-548 has demonstrated a positive benefit-risk profile in Phase 2 and we are working with urgency to bring forward a medicine that delivers effective pain control without addictive potential to patients who are waiting,” she added.
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