Topline Findings
- VX-993 misses endpoint in Phase II trial: Vertex’s selective NaV1.8 inhibitor failed to outperform placebo or hydrocodone/acetaminophen in treating post-surgical acute pain.
- Vertex halts further development of VX-993: The company will not advance VX-993 as a monotherapy due to lack of superior efficacy compared to other NaV1.8 candidates in its pipeline.
- Unmet need remains in acute pain treatment: With 85,000 new cases of opioid use disorder annually, the demand for non-addictive, effective pain therapies continues to grow.
Results from a Phase II trial (NCT06619847) show that Vertex Pharmaceuticals’ VX-993, a selective NaV1.8 inhibitor, failed to meet the primary endpoint treating acute pain following bunionectomy surgery. The company concluded that as a result of the findings, it will not advance VX-993 into pivotal trials as monotherapy in acute pain because it does not offer superior efficacy over existing NaV1.8 inhibitors in its pipeline.1
How Did Vertex’s VX-993 Compare with Existing NaV1.8 Pain Therapies?
“This proof-of-concept study was powered to test whether VX-993 would result in higher clinical efficacy than previously demonstrated with the NaV1.8 pathway,” said Carmen Bozic, MD, EVP, global medicines development and medical affairs, chief medical officer, Vertex Pharmaceuticals, in a press release.
Trial Design and Findings
- The randomized, double-blind, placebo-controlled, dose-ranging trial evaluated the safety and efficacy of VX-993 for acute pain after a bunionectomy in 367 patients and also included a hydrocodone bitartrate/acetaminophen (HB/APAP) reference arm.
- Patients were randomly assigned to five groups: three different dose levels of VX-993 (high, mid, and low), a reference arm receiving HB/APAP (5 mg/325 mg every six hours), and a placebo group.
- Dosing for VX-993 occurred at intervals over 48 hours, starting with an initial dose followed by three additional doses at 12-hour intervals.
- The primary endpoint of the trial was the time-weighted Sum of the Pain Intensity Difference over the first 48 hours of treatment (SPID48), as recorded on the 11-point Numeric Pain Rating Scale, compared to placebo.2
- Patients in the high-dose group demonstrated a 74.5-point reduction based on SPID48, while the mid-dose and low-dose groups demonstrated a 71.5 and 54-point reduction, respectively.
- Patients in the placebo group demonstrated a 50.2-point reduction based on SPID48.
- Notably, patients in the HB/APAP reference arm showed significant pain relief, with a SPID48 of 94.4.
- VX-993 was reported to be well tolerated across all doses. The rate of adverse events (AEs) in the treatment arms were comparable to placebo.
- Common AEs included nausea, headache, dizziness, and vomiting, all of which were generally consistent with the post-surgical setting.
- No serious AEs were linked to VX-993 and there were no treatment discontinuations due to AEs.1
Vertex’s Broader NaV1.8 Strategy
In January, the FDA approved Vertex’s Journavx (suzetrigine), the company’s first NaV1.8 inhibitor aimed at treating moderate-to-severe acute pain in adults. The medication delivers effective pain relief without showing signs of addiction risk, making it the first new type of acute pain treatment authorized in more than 20 years.3
Financial Outlook
Despite the setback, Vertex reported strong financial results for Q2 2025, with total revenue rising 12% to $2.96 billion. Notably, the company saw 14% revenue growth in the United States and 8% internationally. Net income rebounded to $1 billion GAAP.4
The Unmet Need in Acute Pain Management
According to Vertex, roughly 80 million Americans receive medication for acute pain each year, with nearly half prescribed opioids to manage their symptoms. Many of these patients go on to develop opioid use disorder within a year of treatment—an estimated 85,000 new cases annually in the United States. Although alternatives such as acetaminophen and nonsteroidal anti-inflammatory drugs are available, their effectiveness is often limited, particularly for moderate-to-severe pain, highlighting a significant unmet need in pain management.3
“Based on these results, as well as the totality of preclinical data and results from our previous bunionectomy clinical studies, VX-993 is not expected to be superior to our existing NaV1.8 inhibitors and therefore we will not be advancing it as monotherapy in acute pain,” continued Bozic, in the press release.
References
- Vertex Announces Results from Phase 2 Study of VX-993 for the Treatment of Acute Pain. Vertex. August 4, 2025. Accessed August 5, 2025. https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-results-phase-2-study-vx-993-treatment-acute
- A Study Evaluating Efficacy and Safety of VX-993 for Acute Pain After a Bunionectomy. Clinicaltrials.gov. Accessed August 5, 2025. https://clinicaltrials.gov/study/NCT06619847?term=VX-993&aggFilters=phase:2&rank=1
- FDA Approves Vertex Pharmaceuticals’ First-in-Class Non-Opioid Journavx for Moderate-to-Severe Acute Pain. PharmExec. January 31, 2025. Accessed August 5, 2025. https://www.pharmexec.com/view/fda-approves-vertex-pharmaceuticals-first-class-non-opioid-journavx-moderate-severe-acute-pain
- Vertex Reports Second Quarter 2025 Financial Results. Vertex. August 4, 2025. Accessed August 5, 2025. https://investors.vrtx.com/news-releases/news-release-details/vertex-reports-second-quarter-2025-financial-results
