Vertex’s decision to double down on a pain program has delivered a phase 2 win. The biotech linked its NaV1.8 inhibitor VX-548 to statistically significant improvements in pain intensity in people with painful diabetic peripheral neuropathy (DPN), encouraging it to start planning a pivotal program.
Boston-based Vertex committed to testing VX-548 in neuropathic pain after reporting positive phase 2 data in patients with acute pain last year. The expansion of the program led to the initiation of a phase 2 trial of 192 DPN patients one year ago. In the study, participants received one of three doses of VX-548 or pregabalin, the active ingredient in Pfizer’s DPN drug Lyrica.
After 12 weeks of treatment, mean scores on the 11-point Numeric Pain Rating Scale (NPRS) fell by between 2.11 and 2.26 in the three VX-548 arms. All the results were statistically significant improvements from baseline.
As in the acute pain phase 2, Vertex included an active reference arm in the DPN study. The pregabalin cohort was added to provide context and inform the pivotal program, but the trial lacked the power to make statistical comparisons between the arms. Vertex linked pregabalin to a mean NPRS improvement of 2.09, a slightly smaller reduction than was seen in recipients of its drug candidate.
Matching the mean reduction achieved by pregabalin, a gabapentinoid, may be enough for Vertex. At an investor event last month, Stuart Arbuckle, chief operating officer at Vertex, said gabapentinoids have “variable” efficacy and a “significant tolerability profile.” VX-548 is given less frequently, once daily versus three times a day.
The shortcomings of the incumbent drugs leave Vertex with different ways to gain an advantage. “Overall, we're looking for a better benefit-risk profile,” Arbuckle said. “That could be better efficacy, that could be equivalent efficacy and better side effects.”
No serious adverse events were seen in any cohort. There were variations in the most common adverse events, though, with Vertex seeing lower rates of dizziness, peripheral edema and weight increase in the VX-548 arms. The rate of creatinine clearance decrease was higher on VX-548.
Based on the data, Vertex plans to talk to regulators about running a pivotal program in DPN. The biotech is already running pivotal trials in acute pain and expects to report data in the first quarter of next year.
Vertex also recently began a phase 2 trial in another form of neuropathic pain, known as painful lumbosacral radiculopathy (LSR), which has no FDA-approved drugs. According to Arbuckle, “40% of the 10 million patients treated for neuropathic pain in the U.S. are treated because they have a diagnosis of LSR.” It has taken longer to get started in LSR because of the lack of regulatory precedent but the opportunity is big.
Investors seemed pleased with this morning's news, sending shares in Vertex up 7% to $384.50 in premarket trading Wednesday.