Vertex's Pain Relief Breakthrough: VX-548 Moves Closer to Patients After FDA Milestones

Vertex Pharmaceuticals is making significant strides in redefining pain management with its investigational drug suzetrigine (VX-548), an oral selective sodium channel inhibitor targeting NaV1.8. The company has recently achieved multiple regulatory milestones that could position this compound as the first non-opioid pain treatment in its class for over two decades.

Accelerating the Acute Pain Path

The FDA has granted a rolling submission for suzetrigine’s New Drug Application (NDA) in moderate-to-severe acute pain, following impressive Phase 3 trial results announced earlier this year. Vertex has already initiated the rolling submission process and expects to complete the full filing during the second quarter of 2024. This accelerated pathway—supported by previous Fast Track and Breakthrough Therapy designations—reflects the drug’s favorable safety and efficacy profile.

Acute pain represents a massive clinical opportunity: approximately 80 million Americans receive pain medications annually, yet treatment options remain limited. By targeting the NaV1.8 channel, a voltage-gated sodium channel critical to peripheral pain signaling, suzetrigine offers a novel mechanism without the addictive risks associated with opioids.

Expanding Into Neuropathic Pain

Beyond acute indications, Vertex is advancing suzetrigine into peripheral neuropathic pain management. The company recently completed a successful end-of-phase 2 meeting with the FDA following positive Phase 2 data in diabetic peripheral neuropathy (DPN). Building on this momentum, the FDA has awarded suzetrigine Breakthrough Therapy designation for DPN treatment—a recognition of the drug’s potential in addressing a significant unmet medical need.

Vertex plans to initiate a Phase 3 pivotal program in DPN patients during the second half of 2024. The program will comprise two identical 12-week studies enrolling approximately 1,100 patients each, evaluating daily dosing at 70 mg. The primary efficacy measure will assess weekly average pain intensity reduction on a numeric pain rating scale at Week 12 compared to placebo, with pregabalin serving as an active comparator for secondary endpoints.

Following the randomized controlled phase, patients will have the opportunity to continue into an open-label extension study, allowing Vertex to gather long-term safety and effectiveness data in the DPN population.

Broader Portfolio Development

Vertex’s commitment to pain innovation extends beyond suzetrigine. The company continues progressing additional NaV1.8 and NaV1.7 inhibitors as standalone therapies or combination approaches for acute and neuropathic pain conditions.

The next-generation NaV1.8 inhibitor VX-993 is expected to enter Phase 2 clinical studies later in 2024, initially for acute pain and peripheral neuropathic pain indications. Additionally, Vertex anticipates launching a Phase 1 trial of an intravenous VX-993 formulation within the same timeframe, expanding the drug’s potential applications.

Addressing Unmet Medical Needs

Peripheral neuropathic pain affects an estimated 10 million Americans annually who receive pharmaceutical interventions. Conditions like DPN and lumbosacral radiculopathy (LSR)—caused by nerve root impairment in the lumbar spine region—remain challenging to treat effectively with existing therapies.

Vertex’s ongoing Phase 2 LSR study continues enrollment on schedule, with completion targeted for year-end. This expansion demonstrates the company’s systematic approach to evaluating VX-548 across multiple pain syndromes with distinct underlying mechanisms.

The NaV1.8 Advantage

Suzetrigine’s selectivity for the NaV1.8 channel represents a key differentiator. This genetic target has been validated for pain management, and the drug’s highly selective profile suggests a potentially favorable tolerability window compared to non-selective sodium channel blockers. The clinical program—spanning three Phase 3 and two Phase 2 studies—has consistently demonstrated this benefit-risk balance across patient populations.

By creating a new class of selective pain signal inhibitors, Vertex aims to deliver meaningful relief to millions while circumventing the limitations of conventional therapies and opioid-related risks.