Vertex Pharmaceuticals' investigational non-opioid pain medication, VX-548, has shown promising results in late-stage trials, offering a potential alternative to opioids for pain management. The drug demonstrated statistically significant improvement in pain compared to placebo in abdominoplasty and bunionectomy randomized controlled trials, along with a clinically meaningful reduction in pain from baseline.
The Need for Non-Opioid Alternatives
Pain affects tens of millions of Americans daily, and while opioid prescriptions have decreased since 2012, they remain a common treatment. In 2020, approximately 143 million opioid prescriptions were dispensed in the U.S., according to the Centers for Disease Control and Prevention. Despite their effectiveness and low cost (due to many being generic), prescription opioids carry risks of misuse, abuse, and diversion, fueling the need for non-opioid options.
VX-548 Clinical Trial Results
VX-548, a small molecule pill, showed promise in reducing pain after abdominoplasty and bunionectomy surgeries. However, it did not outperform a combination of acetaminophen and hydrocodone for post-surgical pain relief. In the bunionectomy study, the opioid comparator provided better pain relief than VX-548. Vertex is also exploring VX-548 for chronic pain, where the risk of opioid addiction is greater, with mid-stage studies showing potential in reducing pain in people with diabetic chronic nerve pain.
Historical Challenges in Non-Opioid Development
The path to successful clinical development of non-opioid treatments has been challenging. Previous investigational treatments from Acadia and Biogen failed to reach the finish line. Tanezumab, developed by Pfizer and Eli Lilly for osteoarthritis pain, faced safety issues, including joint destruction and rapidly progressive osteoarthritis. An FDA panel recommended rejecting tanezumab due to risk-benefit concerns, and its development was halted.
Existing Non-Opioid Options
Two non-opioid alternatives for acute post-surgery pain relief are available: Zynrelef (bupivacaine with meloxicam) and Exparel (bupivacaine liposome). Zynrelef combines a local anesthetic with a non-steroidal anti-inflammatory drug to relieve post-operative pain after surgeries like bunionectomy, open inguinal herniorrhaphy, or total knee arthroplasty. Exparel is indicated for pain following a wide range of surgeries. Both can reduce or eliminate the need for opioids.
Reimbursement Hurdles
Non-opioid treatments often face reimbursement challenges from insurers, even after FDA approval. A 2018 Department of Health and Human Services report highlighted that insurers often don't pay for non-opioid therapies that are more expensive than generic opioids. Payers may be reluctant to cover VX-548 without clear evidence that it works as well as or better than opioids.
Managing pain requires balancing the benefits and risks of opioid and non-opioid medications. Despite the need for non-opioid alternatives, entering the pain market remains a difficult task.
