Vertex Pharmaceuticals has announced positive results from two Phase 3 clinical trials evaluating VX-548, an investigational non-opioid pain medication, for the treatment of moderate to severe acute pain. The trials focused on patients experiencing post-operative pain following abdominoplasty (tummy tuck) and bunionectomy (bunion removal) procedures. The data suggest VX-548 could offer a much-needed alternative to opioids, addressing concerns about addiction and other adverse effects.
Efficacy and Safety Data
The two randomized, double-blind, placebo-controlled trials enrolled 1,118 abdominoplasty patients and 1,073 bunionectomy patients. VX-548 demonstrated a statistically significant improvement in pain relief compared to placebo, as measured by the time-weighted sum of pain intensity difference over 48 hours (SPID48). In the abdominoplasty study, VX-548 scored 118.4 on the SPID48 scale, compared to 70.1 for placebo. In the bunionectomy study, the scores were 99.9 for VX-548 and 70.6 for placebo. These results were deemed clinically meaningful by Vertex.
In addition to the placebo-controlled trials, VX-548 was compared to hydrocodone bitartrate/acetaminophen, a commonly prescribed opioid combination. While VX-548 did not demonstrate superiority to the opioid combination in both trials, it showed similar pain relief on the Numeric Pain Rating Scale. Notably, VX-548 was generally well-tolerated, with adverse events such as nausea, headache, and constipation occurring less frequently than in the opioid or placebo groups.
Mechanism of Action
VX-548 is a selective inhibitor of the NaV1.8 sodium channel, which plays a crucial role in transmitting pain signals from peripheral nerves to the spinal cord. By selectively blocking this channel, VX-548 aims to reduce pain without affecting the central nervous system, potentially avoiding the addictive properties and other side effects associated with opioids. This mechanism differs significantly from opioids, which act on the brain to reduce pain perception.
Clinical Significance and Future Directions
The positive Phase 3 results for VX-548 represent a significant step forward in the development of non-opioid pain medications. With the ongoing opioid crisis, there is a critical need for effective and safe alternatives for managing acute pain. Vertex plans to submit a New Drug Application (NDA) to the FDA by mid-2024, seeking approval to market VX-548 for moderate to severe acute pain.
"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," said Jessica Oswald, a specialist in emergency and pain medicine at the University of California San Diego, who sits on Vertex’s pain steering committee.
Vertex is also investigating VX-548 for the treatment of chronic pain conditions, including diabetic peripheral neuropathy. Data from a mid-stage study in diabetic nerve pain were reported in December, suggesting potential efficacy in this difficult-to-treat condition. Further studies are underway to evaluate the long-term safety and efficacy of VX-548 in various pain settings.
Market Potential
Analysts predict that VX-548 could achieve peak annual sales of $5 billion or more if approved with a broad label for acute pain. The drug has already received Breakthrough Therapy and Fast Track designations from the FDA, which could expedite its review and approval process.
