Vertex Pharmaceuticals has commenced a rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for suzetrigine (formerly known as VX-548) for the treatment of moderate-to-severe acute pain. The company anticipates completing the NDA submission in the second quarter of 2024. This submission is supported by positive results from Vertex's Phase III program evaluating suzetrigine in acute pain management.
Phase III Trial Results
In January 2024, Vertex announced that suzetrigine met the primary endpoints in three Phase III studies. These studies included two pivotal Phase III acute pain trials following bunionectomy and abdominoplasty surgeries, as well as a 14-day single-arm Phase III study across a range of surgical and non-surgical acute pain conditions. The data indicated that suzetrigine led to a significant reduction in pain intensity across these varied pain conditions and settings.
Suzetrigine for Neuropathic Pain
Vertex is also developing suzetrigine for neuropathic pain. In December 2023, the company reported positive data from a Phase II study of VX-548 in painful diabetic peripheral neuropathy (DPN). The trial demonstrated a statistically significant and clinically meaningful reduction in pain intensity with suzetrigine treatment. Following discussions with the FDA, Vertex is preparing to initiate a pivotal Phase III program of suzetrigine in DPN patients in the second half of 2024.
The planned Phase III program for DPN will consist of two identical 12-week randomized studies assessing the efficacy and safety of suzetrigine (70 mg once daily) compared to placebo in approximately 1,100 patients each. The primary endpoint for both studies is the change from baseline in the weekly average of daily pain intensity on the numeric pain rating scale (NPRS) at week 12 compared to placebo. A key secondary endpoint is the change from baseline in weekly average daily pain intensity on the NPRS at week 12 compared to pregabalin. Patients completing the Phase III studies will have the option to enroll in an open-label study to evaluate the long-term safety and effectiveness of suzetrigine in DPN.
Additional Studies
Vertex is also conducting a Phase II study of suzetrigine in patients with painful lumbosacral radiculopathy. Enrollment in this mid-stage study is expected to be completed by the end of 2024.
Mechanism of Action and Market Potential
Suzetrigine is an investigational, orally administered, selective NaV1.8 pain signal inhibitor. Vertex believes suzetrigine has the potential to become a new standard of care for neuropathic pain, an area with limited treatment options that often rely on highly addictive opioid-based medications. In addition to suzetrigine, Vertex is developing other preclinical and clinical NaV1.8 and NaV1.7 pain signal inhibitors, both as monotherapies and in combination, for treating acute and neuropathic pain. The company plans to initiate Phase II studies on its next-generation NaV1.8 pain signal inhibitor, VX-993 oral formulation, for acute pain and peripheral neuropathic pain later in 2024, and a Phase I study of an intravenous formulation of VX-993 in 2024.
Suzetrigine has been granted Fast Track and Breakthrough Therapy designations by the FDA for moderate-to-severe acute pain and for pain associated with DPN.
