FDA Accepts Vertex NDA for Suzetrigine, Investigational Oral Nonopioid Analgesic for Acute pain

If approved the selective NaV1.8 pain signal inhibitor would reflect the first new class of pain management medication in more than 20 years.

The FDA recently accepted a new drug application (NDA) for suzetrigine, an investigational oral non-opioid agent for treatment of moderate-to-severe acute pain, according to biotech company Vertex.

The selective NaV1.8 pain signal inhibitor was previously granted Fast Track and Breakthrough Therapy designations by the FDA and the agency has set a Prescription Drug User Fee (PDUFA) target action date of January 30, 2025, Vertex stated in its announcement.1

If approved, suzetrigene could represent the first new class of medications for treatment of acute pain in more than 2 decades.

With the opioid epidemic a persistent headline news story and continued reluctance among many clinicians to prescribe the narcotic analgesics, there has been an urgent need for pain medications that provide relief without the significant risks. Nonsteroidal anti-inflammatory drugs (NSAIDs) carry their own risks, including the potential for gastrointestinal bleeding and renal complications.

“Today’s FDA filing acceptance for suzetrigine marks a critical milestone toward bringing this new, transformative non-opioid analgesic to the millions of patients suffering from moderate-to-severe acute pain each year in the US,” Nia Tatsis, PhD, executive vice president, chief regulatory and quality officer at Vertex, said in the press release.1 “The FDA’s granting of a priority review further reinforces the high unmet need in treating acute pain, and the filing brings us one step closer to our objective of filling the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential.”1

Suzetrigine is an investigational oral, selective NaV1.8 pain signal inhibitor that is highly selective for NaV1.8 relative to other NaV channels, explained Vertex. The NaV1.8 voltage-gated sodium channel is found in peripheral nociceptive neurons and transmits pain signals. NaV1.8 also has been genetically validated as a target for the treatment of pain.1

In January, Vertex announced positive results from 2 phase 3 clinical trials in which suzetrigine was used to treat moderate to severe acute pain following bunionectomy and abdominoplasty surgeries.2 Each trial met its primary endpoints, resulting in a statistically significant improvement of the time-weighted sum of the pain intensity difference from 0 to 48 hours compared to placebo as well as a clinically meaningful reduction in pain from baseline at 48 hours on the Numeric Pain Rating Scale.2 Neither trial, however, met the key specified secondary endpoint, superiority over pain relief obtained with use of hydrocodone/acetaminophen in the studies’ control group.2

In a phase 3 single-arm safety and effectiveness study, investigators evaluated treatment with suzetrigine for up to 2 weeks across a variety of surgical and nonsurgical pain conditions and reported a favorable safety profile with no serious adverse events.2 Further, 83.2% of study participants rated suzetrigene as good/very good/excellent at treating pain as measured by a Patient Global Assessment following treatment.2

“We are very pleased with the results from the VX-548 pivotal program, which demonstrate a compelling and consistent combination of efficacy and safety across multiple acute pain conditions and settings,” Tatisis said in an earlier press announcement.2

"In my 24 years practicing medicine, I have seen firsthand the desperate need for new non-opioid therapies for treating pain. Too many people today are either undertreated, dealing with negative side effects of currently available therapies or foregoing pain medications altogether for fear of becoming dependent on opioids,” Scott Weiner, MD, MHP, acute pain steering committee chair at Vertex, associate professor of emergency medicine at Brigham and Women’s Hospital, said in the announcement of the NDA. “Prescribers and patients deserve new options."1

1. Vertex announces FDA acceptance of new drug application for suzetrigine for the treatment of moderate-to-severe acute pain. News release. Vertex. July 30, 2024. Accessed August 15, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-fda-acceptance-new-drug-application-suzetrigine
2. Vertex announces positive results from the VX-548 phase 3 program for the treatment of moderate-to-severe acute pain. News release. Vertex. January 30, 2024. Accessed August 15, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-positive-results-vx-548-phase-3-program