After phase 3 hit, Spine seeks path forward for pain drug

The first phase 3 readout with Spine BioPharma's drug candidate for chronic low back pain (CLBP) has proved disappointing, but the company still believes there is a way forward for the programme.

The MODEL trial of Spine's vicatertide (SB-01), a TGF-β antagonist, is testing the drug as an injection between the discs of the spine in CLBP patients with degenerative disc disease, but did not achieve its objective of showing a reduction in pain intensity and pain-related function after six months compared to a sham control.

The New York-based biotech has put the negative result down to a better-than-expected outcome in patients treated with the sham injection in the 417-subject study, and is now hoping to meet with the FDA to discuss a way to bring vicatertide to market.

All told, 67% of patients in the treatment arm met the disability and pain primary endpoint response criteria at six months, falling to 62% at 12 months, which Spine said was a "clinically meaningful" improvement even if it did not pass the threshold for significance.

Safety in the study was in line with an earlier phase 2 trial, according to Spine, which pointed to trends towards improvement in pain intensity and pain-related function – which extended out to 12 months – as evidence that further development of the drug in CLBP is worth pursuing.

The sham responses were more apparent in some investigator sites in the trial, according to the biotech, and stripping those out of the dataset revealed a benefit for vicatertide that flirted with statistical significance, with a p-value of 0.051.

"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 CLBP studies," said Fran Magee, Spine's chief technology officer.

"We are surprised by the very high sham control response in this study that kept us from achieving statistical significance," she added.

The disappointing result comes amid a push by the biopharma industry to come up with alternatives to opioid-based analgesics for chronic pain indications that can reduce the well-documented risks of dependency and overdose.

Vertex already has FDA approval for NaV1.8 inhibitor Journavx (suzetrigine) in acute pain, with late-stage trials on the go in chronic, neuropathic pain indications, while other companies with candidates in mid- to late-stage development include Eli Lilly, Algiax, Latigo Bio, Vertanical, and Tris Pharma.

Photo by Julien Tromeur on Unsplash