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Thursday, June 13, 2019

Questions surround Bone Therapeutics’ spine data

The company needed a hit in its spine trial, and it claims to have got one.
The disastrous halting of a trial of Bone Therapeutics’ cell therapy Preob in hip osteonecrosis last autumn left the Belgian group in a precarious position. It is now claiming a hit with its one real remaining hope, the allogeneic osteoblast product Allob, in a phase IIa study in lumbar spinal fusion, and the company’s stock is up 9% so far today.
But with no control group the study does not settle the question of how much of the benefit seen was actually conferred by Allob.
Today’s news appears good. The trial enrolled 30 patients with degenerative spine disorders to whom Allob was administered at the surgical site during the standard fusion procedure for the lumbar vertebrae. This standard treatment involves the surgical implantation of an interbody cage with bioceramic granules into the spine.
Fusion
A year after the procedure successful fusion was seen on CT scans in in 22 out of 30 patients (73.3%). Bone Therapeutics gives a p value for this – less than 0.001 – despite the trial having no control group. It is comparing the one-year outcomes to baseline, in which case it is hardly surprising that there was an improvement.
Indeed, owing to the trial’s design, it is impossible to say whether the improvement was down to the inclusion of Allob or simply the standard spinal fusion procedure.
“How can we be sure the efficacy is coming form Allob? Obviously without a control we will never be sure,” Thomas Lienard, Bone Therapeutics’ chief executive, told Vantage on a conference call to discuss the results. He said that the trial’s objective was not to go head-to-head with another type of treatment but rather to have information on the safety of Allob and indications of its efficacy.
Professor Bronek Boszczyk, head of spinal surgery at Benedictus Hospital, Tutzing, Germany, said the trial was a cohort study, and as such the control group would be historical data from other studies.
“We believe the results are strong compared with the standard procedure alone,” Mr Lienard added.
Fracture trial
In its press release, the company added that the other eight patients showed evidence of bone formation, and said that 13 of the first 15 patients who reached the 24-month follow-up time point (86.7%) showed successful fusion.
It then stated that “treatment with Allob resulted in a clear and statistically significant clinical improvement from the pre-treatment baseline in functional disability” since 63% of the trial patients had improvements on the Oswestry Disability Index. It again gives a p value of less than 0.001. But again the data do not show that this improvement can be definitively attributed to Allob.
The company now plans to push Allob forward in its other indication, delayed-union or non-union fractures, with a phase II/III trial pencilled in for next year. The next steps in spinal fusion are not yet clear.
Perhaps it is not unusual for a phase IIa trial to dispense with a control group. But claiming statistical significance under these circumstances looks disingenuous.

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