In both randomised controlled trials for abdominoplasty and bunionectomy, treatment with VX-548 resulted in a statistically significant improvement in pain compared to placebo, alongside a clinically meaningful reduction in pain from baseline
Vertex Pharmaceuticals plans to file an NDA for VX-548 with the FDA by mid-2024. (Credit: Vertex Pharmaceuticals Incorporated)
Vertex Pharmaceuticals said that the Phase 3 programme for its selective NaV1.8 inhibitor VX-548 in the treatment of moderate-to-severe acute pain has yielded positive results.
The programme comprised two late-stage trials, conducted in a randomised, double-blind, placebo-controlled manner, focusing on abdominoplasty and bunionectomy surgeries. The trials included 1,118 patients who underwent abdominoplasty and 1,073 patients undergoing bunionectomy.
Additionally, a safety and effectiveness study, with a single-arm design, included 256 patients with various surgical and non-surgical pain conditions.
In both studies following abdominoplasty or bunionectomy surgery, treatment with VX-548 resulted in a statistically significant improvement in the primary endpoint, said Vertex Pharmaceuticals. Specifically, there was an enhancement in the time-weighted sum of the pain intensity difference from 0 to 48 hours (SPID48) compared to placebo.
Additionally, there was a clinically meaningful reduction in pain from baseline at 48 hours on the Numeric Pain Rating Scale (NPRS) observed in both trials.
The US-based biotechnology company assessed VX-548’s superiority over hydrocodone bitartrate/acetaminophen (HB/APAP) on the SPID48 following abdominoplasty or bunionectomy surgery for the first key secondary endpoint. However, neither trial achieved this key secondary endpoint.
In both trials, the second key secondary endpoint assessed the time to achieve meaningful pain relief, defined as a ≥2-point reduction in NPRS from baseline compared to placebo. The NaV1.8 inhibitor exhibited a faster onset of meaningful pain relief than placebo in both abdominoplasty and bunionectomy trials.
Other secondary endpoints across both trials were mostly in line with the primary endpoint. Additionally, VX-548 demonstrated safety and good tolerability in all three Phase 3 studies.
The company said that it intends to file a new drug application for the NaV1.8 inhibitor with the US Food and Drug Administration (FDA) by mid-2024, aiming for a comprehensive label covering moderate-to-severe acute pain.
VX-548 has received breakthrough therapy and fast track designations from the FDA for acute pain.
Vertex Pharmaceuticals CEO and president Reshma Kewalramani said: “We are very pleased with the results from the VX-548 pivotal programme, which demonstrate a compelling and consistent combination of efficacy and safety across multiple acute pain conditions and settings.
“The VX-548 benefit-risk profile ideally positions it to potentially fill the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential.”
“With FDA Breakthrough and Fast Track Designations in hand, we are working with urgency to file the New Drug Application for VX-548 and bring this non-opioid medicine to the millions of patients who suffer from acute pain each year in the U.S.”
Earlier this month, Vertex Pharmaceuticals secured FDA approval for Casgevy (exagamglogene autotemcel [exa-cel]) in transfusion-dependent beta thalassemia (TDT) in patients 12 years and older.