A phase 3 trial of Spine BioPharma’s chronic low back pain candidate has missed its primary endpoint. But, with the biotech pinning the failure on a “very high sham control response,” management plans to meet with the FDA to discuss a potential path to market.
The trial enrolled 417 patients with chronic low back pain associated with degenerative disc disease. Half of the patients were randomized to receive one injection of the company’s TGF-β antagonist SB-01 into the affected intervertebral disc. The rest of the patients were randomized into a sham control arm.
After six months, investigators assessed changes in patients’ scores on a disability index and pain scale. ClinicalTrials.gov lists the disability index as the primary endpoint. The pain scale is listed as a secondary endpoint that will only be tested if the primary endpoint is met. In its Aug. 1 press release to disclose the data, Spine BioPharma said the primary endpoint looked at changes in both the disability and pain scores.
Sixty-seven percent of patients in the SB-01 arm met the disability and pain primary endpoint response criteria. The company said the result was clinically meaningful and consistent with the phase 2 findings. Fran Magee, Spine BioPharma’s chief technology officer, explained where the trial went wrong in a statement.
“The sham control response was statistically significantly higher than observed in the phase 2 study. The statistical design of this phase 3 study anticipated a high sham control success, as observed in the phase 2 study and typically seen in [chronic low back pain] studies,” Magee said. “We are surprised by the very high sham control response in this study that kept us from achieving statistical significance.”
Spine BioPharma said the high sham response was only observed at certain sites. For a subset analysis, the company focused on 227 patients from sites with an anticipated sham response rate consistent with its phase 2 study. In that analysis, 70% of patients in the SB-01 arm and 59% in the control arm met the primary endpoint response criteria.
The company now plans to complete its data analysis and meet with the FDA. Spine BioPharma intends to share the phase 3 results alongside data from phase 1 and 2 studies to explore potential pathways for the approval of SB-01.