Vertex posts full pain data ahead of FDA ruling, unpacking combo results, Vicodin miss and stellar safety

Vertex has reported phase 3 data on its near-approval pain drug candidate suzetrigine, shedding light on how the non-opioid painkiller combines with ibuprofen and why the prospect failed to match a Vicodin equivalent in one of the studies.

The Big Biotech reported top-line data from the studies in January. At that time, Vertex said its NaV1.8 inhibitor suzetrigine, then called VX-548, significantly improved pain intensity compared to placebo in the 48 hours after patients underwent tummy tucks and bunionectomies. The results caused the trials to hit their primary endpoints, but a common pain drug matched, and, in one study, beat, suzetrigine.

Vertex used the American Society of Anesthesiologists’ annual meeting to share and discuss data from the trials. Todd Bertoch, M.D., an anesthesiologist and lead investigator on the trials, presented the data and fingered the use of a local anesthetic before bunionectomy patients were randomized as an explanation for why suzetrigine had little effect on pain in that population in the hours after dosing.

“Ropivacaine local anesthetics are very nonselective inhibitors of sodium channels in general,” Bertoch said. “What we believe is that there's some still residual circulating ropivacaine impacting some percentage of the NAV1.8 channel, so, after suzetrigine is dosed, the efficacy appears to be diminished because you can't inactivate a channel that's already inactivated by the ropivacaine.”

That theory could explain why single-agent suzetrigine was no better than placebo at improving pain in bunionectomy patients in the six hours or so after dosing. Scores in the suzetrigine arm separated from placebo after that, resulting in a statistically significant improvement after 48 hours, but suzetrigine never made up the ground lost to the Vicodin equivalent in the early hours of the study. Evercore ISI analysts said in a note to investors that suzetrigine probably won’t be recommended in combination with ropivacaine.

Bertoch’s presentation also broke out the data on people who received suzetrigine as a monotherapy and their counterparts who also took ibuprofen. The analysts said the use of suzetrigine on top of the nonsteroidal anti-inflammatory drug (NSAID) is “akin to the real-world setting,” making it an important test. Suzetrigine passed the test, beating placebo when paired with a NSAID in both trials.

“Suzetrigine will be positioned between NSAIDs and entry level opioid as an add-on to NSAIDs/Tylenol for those who need more pain control, or as an alternative to NSAIDs for those who are intolerant,” the analysts said.

Other analysts also took encouragement from the presentation. The team at William Blair called the data “an incremental positive for the trajectory of suzetrigine to infiltrate the acute pain market,” adding that they believe the molecule “has a strong argument for inclusion in the market.” 

Leerink Partners analysts are forecasting annual sales of $866 million in 2026, compared to a consensus of $362 million.

The forecasts reflect the evidence that suzetrigine reduces pain without the abuse potential of opioids. Suzetrigine had a clean safety profile in the phase 3 trials. Bertoch, who has been principal investigator on more than 150 clinical trials, said the program represents the first time he has seen a study drug have fewer adverse events than placebo.

One outstanding question is whether payers will embrace suzetrigine. William Blair analysts said “pricing remains a point of investor contention along with how this impacts reimbursement, formulary placement and prior authorization requirements.” Evercore analysts assume prior authorization will be required, given the large potential size of the market, but Vertex is hoping to avoid that requirement.

“We're looking for broad access, no prior authorization, because clearly that would be a barrier to quick access for the patients to get the product when they really need it,” Duncan McKechnie, head of North America commercial at Vertex, said.

Vertex began talking to payers 11 months ago. The talks have laid the foundation for a launch that is now on the horizon. The FDA is set to rule on whether to approve suzetrigine by Jan. 30. Leerink analysts said they think the FDA could reach a decision ahead of the deadline because of the need for alternatives to opioids in the treatment of acute pain.