Vertex has announced preclinical data and the results from its Phase II proof-of-concept trials evaluating treatment with the selective, oral NaV1.8 inhibitor VX-548 for acute pain following abdominoplasty and bunionectomy surgeries. VX-548 is a non-opioid pain reliever. These results were published in the New England Journal of Medicine (NEJM).
“VX-548 preclinical studies demonstrated high selectivity and potency for the NaV1.8 sodium channel which translated into Phase II clinical results with strong efficacy, a favorable benefit-risk profile and promise in the treatment of acute pain,” said Carmen Bozic, MD, executive vice president, global medicines development and medical affairs, and chief medical officer at Vertex.
“There has not been a new class of pain medicine in decades, and we urgently need new treatment options to help the millions of people affected by pain each year in the U.S. The Phase II results from VX-548 show the potential this medicine could bring to patients,” said Scott Weiner, MD, co-author of the NEJM manuscript, associate professor of emergency medicine at Harvard Medical School and Attending Emergency Physician at Brigham and Women’s Hospital.
It’s estimated that there are more than 50 non-opioid drugs in development for postoperative pain. The world market for these drugs is estimated at almost $40B.
VX-548 is an oral, highly selective NaV1.8 inhibitor. NaV1.8 is a voltage-gated sodium channel that plays a critical role in pain signaling in the peripheral nervous system. It is a genetically validated target for the treatment of pain. The NaV1 VGSC family consists of nine members—NaV1.1–1.9 encoded by the SCN1A-SCN5A and SCN8A-SCN11A genes.
Vertex has previously reported clinical proof-of-concept with a small molecule investigational treatment targeting NaV1.8 in multiple pain indications including acute pain, neuropathic pain, and musculoskeletal pain.
The company’s approach is to selectively inhibit NaV1.8 using small molecules with the objective of creating a new class of medicines that have the potential to provide superior relief of pain without the limitations of opioids, including their addictive potential. VX-548 is one of the most recent molecules to enter clinical development from Vertex’s portfolio of NaV1.8 inhibitors.
“Our Phase III trials for VX-548 are well underway, and we look forward to the potential of bringing an effective, non-opioid therapeutic option to patients suffering from moderate to severe acute pain,” Bozic said.
“Acute pain is frequently treated with opioids that come with significant safety and tolerability concerns, including sedation, respiratory depression and the potential for misuse and addiction,” said Weiner.
Vertex says it expects to complete the pivotal program in late 2023 and share results from these studies in late 2023 or early 2024. VX-548 has been granted Breakthrough Therapy and Fast Track designations in the U.S. for moderate to severe acute pain. In addition, the company has initiated a Phase II dose-ranging study of VX-548 in neuropathic pain.
The Phase III program for VX-548 includes two randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of the drug for moderate to severe acute pain following bunionectomy or abdominoplasty surgery. Both studies will also include a hydrocodone bitartrate/acetaminophen treatment arm. A third, single-arm study will evaluate the safety and effectiveness of VX-548 for up to 14 days across multiple other types of moderate to severe acute pain.
