FDA Approves Journavx, First-in-Class Nonopioid Analgesic for Moderate-to-Severe Acute Pain

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The FDA today approved nonopioid Journavx (suzetrigine) for management of moderate to severe acute pain. The novel highly selective voltage-gated sodium channel (NaV1.8) inhibitor, developed by Vertex Pharmaceuticals, is an oral first-in-class analgesic and represents the first new approach to pain management in more than 20 years, the company said in a news release.¹

“Today’s approval is a historic milestone for the 80 million people in America who are prescribed a medicine for moderate-to-severe acute pain each year,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex, in the news release. “With the approval of Journavx, a non-opioid, pain signal inhibitor and the first new class of pain medicine approved in more than 20 years, we have the opportunity to change the paradigm of acute pain management and establish a new standard of care.”¹

“This is an incredible day for patients and physicians alike who now have an approved non-opioid treatment that delivers effective acute pain relief and a favorable safety profile without addictive potential,” said Jessica Oswald, M.D., M.P.H., Associate Physician in Emergency Medicine and Pain Medicine in San Diego and Vertex Acute Pain Steering Committee Member, in the news release. “I believe Journavx could redefine the management of pain and become a foundational treatment option for people with all types of moderate-to-severe acute pain, where options aside from opioids have been so desperately needed.”¹

The sodium channel Na_V1.8 is selectively expressed in peripheral neurons, including neurons of the dorsal-root ganglia that transmit nociceptive signals. An oral, small molecule that is a potent inhibitor of Na_v1.8 currents, suzetrigine is more highly selective for Na_V1.8 than other Na_V channels in vitro. Receptors for Na_V1.8 are essentially undetectable in the human brain.¹ “On this basis, we consider selective Na_V1.8 inhibitors to be unlikely to be associated with central nervous system effects, including potential for abuse and dependence,” wrote researchers in the New England Journal of Medicine.² (Note: these risks were not tested in clinical trials). Selective inhibition of Na_V1.8 has the potential to create a new class of pain signal inhibitors that provide effective pain relief and avoid the addictive potential of opioids, the most frequently used medications used to treat acute pain.¹

“I've been the principal investigator for over 150 clinical trials, many of those in pain, and I've never seen a study where the placebo had more side effects than the study drug, and that was the case [here]. I think the real key here is based on the evidence that we've seen, it appears that we have a drug that's effective in treating pain but has an incredibly safe profile,” phase 3 principal investigator Todd Bertoch, MD, an anesthesiologist and CEO of CenExel JBR Clinical Research in Salt Lake City, UT,” said in an interview with Patient Care.²

The FDA approval is based on positive results from 2 phase 3 pivotal clinical trials in which suzetrigine was used to treat moderate to severe acute pain following bunionectomy and abdominoplasty surgeries. (Jan 30 release) 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.

Additional data was submitted from 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.³ 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.³

Suzetrigine was granted FDA Fast Track and Breakthrough Therapy designations in moderate-to-severe acute pain in the US and was considered for approval under FDA priority review.

The Phase 3 pivotal program for suzetrigine in patients with painful diabetic peripheral neuropathy is ongoing, and the company plans to advance its pivotal program evaluating suzetrigine in patients with painful lumbosacral radiculopathy pending discussions with regulators.

Acute pain is a serious and potentially disabling condition often caused by surgery, accident or injury. Over 80 million Americans are prescribed medicine to treat their moderate-to-severe acute pain every year. Of these, about 40 million are prescribed an opioid. Nearly 10% of acute pain patients treated initially with an opioid will go on to have prolonged opioid use, and about 85,000 patients will develop opioid use disorder annually. Poorly controlled acute pain can lead to reduced quality of life, development of chronic pain, and increased burden on the health care system and society.¹

The most common side effects of suzetrigine include itching, muscle spasms, increased blood level of creatine phosphokinase, and rash. The medication may also temporarily reduce the chance of females becoming pregnant while on treatment, according to the news release.¹

"Renewed Optimism"

Commenting on what he calls the “renewed optimism” for the future of pain management reflected by the suzetrigine research, Bertoch added. “Suzetrigine offers the potential to fill the critically important treatment gap between opioids and other currently available therapies that have either limited efficacy and/or poor tolerability.”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, associate professor of emergency medicine at Brigham and Women’s Hospital and acute pain steering committee chair at Vertex, said in the announcement of the NDA. “Prescribers and patients deserve new options."⁴

Vertex is also evaluating suzetrigine in peripheral neuropathic pain (PNP). The company’s Phase 3 pivotal program for suzetrigine in patients with painful diabetic peripheral neuropathy is ongoing, and the company plans to advance its pivotal program evaluating suzetrigine in patients with painful lumbosacral radiculopathy pending discussions with regulators.¹

References

1. Vertex Announces FDA Approval of JOURNAVX (suzetrigine), a First-in-Class Treatment for Adults With Moderate-to-Severe Acute Pain. News release. Vertex Pharmaceuticals. January 30, 2025. Accessed January 30, 2025. https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-fda-approval-journavxtm-suzetrigine-first-class

2. Journavx Approval: Lead Investigator Highlights Pivotal Phase 3 Clinical Trials. Patient Care Online. Published January 30, 2025. Accessede January 30, 2025. https://www.patientcareonline.com/view/journavx-approval-lead-investigator-highlights-pivotal-phase-3-clinical-trials

3. Jones J, Correll DJ, Lechner SM, et al. Selective inhibition of NaV1.8 with VX-548 for acute pain. N Engl J Med. 2023;389:393-405 doi:10.1056/NEJMoa2209870

4. Vertex announces FDA acceptance of new drug application for suzetrigine for the treatment of moderate to severe acute pain. News release. Vertex Pharmaceuticals. July 30, 2024. Accessed July 30, 2024. https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-fda-acceptance-new-drug-application-suzetrigine