Vertex on the Verge of Breakthrough for Nonopioid Pain Management as NOPAIN Act Takes Effect

Suzetrigine, the investigational oral, highly selective NaV1.8 pain signal inhibitor for the treatment of moderate-to-severe acute pain in development by Vertex is on the FDA’s pharmaceutical drug user fee act (PDUFA) calendar with a date set for a decision of January 30, 2025. If the nonopioid medication is approved, it will be the first in this category to reach the market in more than 20 years.

The potential approval could not be more auspiciously timed. The Non-Opioids Prevent Addiction In the Nation (NOPAIN) Act became effective on January 1, 2025. NOPAIN requires Medicare to provide separate add-on payments for FDA-approved non-opioid pain treatments in hospital outpatient and surgical center settings (both bills). Vertex anticipates that, pending FDA approval, suzetrigine for acute pain will be included among the treatments eligible for these payments, further supporting its integration into clinical practice, according to a company news release.¹ Further, 7 states have recently passed legislation specifying that non-opioid therapies should be prioritized over opioids for pain management in retail pharmacy settings.¹

“Our goal in developing suzetrigine is to deliver the first non-opioid acute pain treatment in more than two decades and to change the paradigm of pain management as we know it,” Carmen Bozic, MD, Vertex executive vice president, global medicines development and medical affairs, chief medical officer said in an October news release.²

Clinical Trial Findings

Suzetrigine is an investigational oral, selective NaV1.8 pain signal inhibitor that is highly selective for NaV1.8 relative to other NaV channels. 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.³

In January 2024, 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.⁴ 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

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

Beyond acute pain management, Vertex is evaluating suzetrigine and its mechanism of action in treatment for chronic neuropathic pain. The company is currently enrolling and dosing participants with diabetic peripheral neuropathy in a phase 3 pivotal trial of suzetrigine. In December, 2024, the company announced results of topline data from a phase 2 trial with suzetrigine in painful lumbosacral radiculopathy and plans to advance the investigational drug into a pivotal development program, “pending discussions with regulators on the study design and regulatory package,” the company said.¹

“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."

NOPAIN Act Details

H.R. 5172
“To amend title XVIII of the Social Security Act to combat the opioid crisis by promoting access to non-opioid treatments in the hospital outpatient setting.”

S. 586
This bill temporarily establishes separate payments for certain non-opioid treatments under the Medicare prospective payment system for hospital outpatient department services and the payment system for ambulatory surgical center services. The bill applies to pain management treatments that are able to replace or reduce opioid consumption, as shown through clinical trials or data.

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