By Pat Anson

New questions are being raised about the effectiveness of an experimental non-opioid analgesic and whether it can be a viable alternative to opioid pain medication.

Results from Vertex Pharmaceuticals’ Phase 2 clinical trial show that suzetrigine is essentially no more effective than a placebo in relieving back and hip pain caused by lumbosacral radiculopathy (LSR).

After 12 weeks of treatment with the drug suzetrigine, patients with LSR had a 2.02 average reduction in their pain scores on a rating scale of zero to 10. That compares to an average reduction of 1.98 for patients who received a placebo or sham treatment.

Although the difference between 2.02 and 1.98 is minuscule, Vertex claimed the overall findings were “statistically significant and clinically meaningful” in a press release. The company blamed the lackluster results on the placebo effect and the difficulty of treating lumbosacral radiculopathy.

“Suzetrigine has again demonstrated its potential to fill an important unmet need in the treatment of pain,” said Carmen Bozic, MD, Executive Vice President and Chief Medical Officer at Vertex. “We did not see separation between the suzetrigine and the placebo arms. Yet our post-hoc analyses suggest that this could be due to the high placebo response in this study.”

Despite the disappointing results, Vertex still plans to go ahead with a Phase 3 study of suzetrigine for LSR, while changing the study design to minimize the impact of the placebo.

“Managing the placebo response in pain trials is a complex challenge. We look forward to innovating in clinical trial design, including for the pivotal study, with the aim of bringing a potentially safe and effective treatment to patients suffering from LSR," said Christine Sang, MD, co-chair of Vertex’s Peripheral Neuropathic Pain steering committee and principal investigator of the study.

Suzetrigine is already under consideration by the FDA as a treatment for acute pain, with a decision expected in late January. If approved, suzetrigine would be the first new medication for acute pain in over two decades.

Unlike opioids, suzetrigine blocks pain signals in the peripheral nervous system before they reach the brain. That means it won’t have the “liking” effect that opioids can have in some patients or be as addictive.

Although suzetrigine has been touted as a novel painkiller that "could bring relief to millions” without the risk of addiction, findings from earlier studies have also been mixed. In a Phase 3 trial of patients recovering from minimally invasive surgery, suzetrigine was no more effective than a low dose combination of hydrocodone and acetaminophen, more commonly known as Vicodin.

Although Vertex downplayed the results from the Phase 2 study, shares of the company lost about 15% of their value after last week’s announcement. Wall Street analysts said the Phase 2 findings were “very messy” and "raise considerable risk around suzetrigine's potential.”

Ultimately, it will be up to the FDA to decide whether suzetrigine should be allowed on the market. The agency is under pressure to approve new non-opioid analgesics, so it may look past the disappointing clinical trial findings. If approval is granted in January, it will coincide with implementation of the NOPAIN Act, which will make non-opioid analgesics in outpatient surgical settings eligible for higher Medicare reimbursement rates.  

In addition to acute pain and lumbosacral radiculopathy, Vertex is also studying suzetrigine as a treatment for diabetic peripheral neuropathy.