Vertex’s long-running attempt to crack the blockbuster pain market has finally delivered a pair of phase 3 wins. And yet, the positive news was tempered by the failure to hit key secondary endpoints designed to show the non-opioid medicine is more effective than an existing, widely-used painkiller.
First, the good news for Vertex. After the biotech discarded a pair of NaV1.8 inhibitors based on early clinical data, a third drug candidate, VX-548, aimed at the sodium channel has beaten placebo in two late-phase clinical trials. The significant improvements in pain intensity in the 48 hours after patients underwent tummy tucks and bunionectomies caused the studies to meet their primary endpoints.
While the primary endpoints compared VX-548 to placebo, Vertex randomized some participants in both trials to take the common pain combination of hydrocodone bitartrate and acetaminophen (HB/APAP). The drug, which is sold as Vicodin, contains the opioid hydrocodone and is frequently abused.
VX-548 had a numerical advantage over HB/APAP in the tummy tuck trial but the difference fell short of statistical significance. In the bunionectomy trial, HB/APAP performed significantly better than VX-548, resulting in a p value of 0.0016. The finding that HB/APAP provides more pain relief than Vertex’s drug candidate in bunion surgery patients complicates the case for VX-548.
Vertex’s pain program has focused on achieving opioid-like efficacy without the abuse potential of that class of effective but problematic medicines. Talking at the J.P. Morgan Healthcare Conference earlier this month, Vertex CEO Reshma Kewalramani discussed the need to fill the “gaping hole in the treatment landscape between acetaminophen and NSAIDs and opioids.”
VX-548’s mechanism “does not hold addictive potential,” Kewalramani said, and the CEO restated her belief that the molecule can fill the gap in the treatment landscape after seeing the phase 3 data. Even so, the failure to beat, and in one trial even to match, the opioid leaves Vertex open to skepticism as it works to persuade payers that VX-548 is a better option than established, relatively cheap alternatives.
That all awaits Vertex down the line. First, the big biotech needs to get VX-548 to market. Vertex plans to file for FDA approval by the middle of the year and is seeking a broad label in moderate-to-severe acute pain. The opportunity is huge, with Vertex estimating acute pain affects more than 80 million people a year in the U.S., a market currently largely served by generic medicines.
Vertex’s push to get VX-548 over the line in acute pain is part of a broader program. The drug candidate came through a phase 2 test in painful diabetic peripheral neuropathy last month, emboldening Vertex to start planning a pivotal program, and the biotech has other NaV1.8 and NaV1.7 inhibitors in clinical and preclinical development with a view to developing monotherapies and combinations.