An early halt for a phase II trial of Bone Therapeutics’ allogeneic cell therapy Allob could bring the project’s approval forward in its lead indication of delayed-union fractures. Coupled with the positive signs with the same project in spinal fusion that emerged last week, Allob is looking good.
In fact it is looking so good that Bone Therapeutics is shelving a phase II/III trial of its lead candidate, the autologous cell preparation Preob, in non-union fractures, to focus on Allob. But Allob is still some way from approval with phase III plans not yet fleshed out, and the trial had no control group, so the data at this point are merely illustrative.
Delayed-union fractures are those where the broken bone fails to knit together within the expected time frame for bone healing – but where healing is expected to occur eventually, without additional surgical or other intervention necessary. By contrast, non-union fractures are those where the healing process is determined to have ceased.
Current standard treatment for both is bone allograft or autograft, a surgical procedure associated with a major complication rate of 20-30%.
The patients in the trial of Allob had delayed-union fractures of a long bone that had been present for three to seven months without healing properly.
The phase I/IIa study’s data safety monitoring board has recommended that it be halted early, stating that interim results from the first 16 patients were sufficient to show the therapy’s efficacy.
All 16 patients met the primary endpoint, defined as either an increase of at least two points in their tomographic union score (TUS) or an improvement of at least 25% in their in their global disease evaluation (GDE) score six months after a single injection of Allob directly into the fracture site.
13 of the 16 patients hit on TUS, which is based on the evaluation of a CT scan, with an average improvement of four points. 12 of the 16 had the minimum 25% improvement on GDE score, with an average improvement of 48%. Pain at the fracture site, a secondary endpoint, was reduced by an average of 59%. All these improvements were statistically significant.
Them’s the breaks
The trial was intended to recruit 35 patients, but after the DSMB’s recommendation recruitment will be stopped immediately and Bone Therapeutics will start preparing for phase III. The company’s hopes for Allob here are so high that a trial of Preob in 176 patients with non-union long bone fractures that has been running for more than five years will now be closed down.
Preob is now in development for only one indication, osteonecrosis of the hip. A phase III trial in 130 patients is ongoing and ought to report final data in early 2019.
Allob saw positive interim data from its trial in lumbar spinal fusion last week. These were not so good that a halt was recommended; the trial will continue until 2018. However once again the group scythed another trial to refocus: this time another of Allob’s trials in rescue fusion is to be halted to pump more resources into the lumbar study.
The company said it would also work to develop Allob for the treatment of other difficult fractures; presumably a study in non-union breaks will be forthcoming.
|Bone Therapeutics' ongoing clinical trials|
|Preob||Phase III||Preob-ON3||130||Osteonecrosis of the hip||NCT01529008||December 2018|
|Allob||Phase IIa||Allob-IF1||38||Lumbar spinal fusion||NCT02205138||April 2018|
|Preob||Phase IIb/III||Preob-NU3||176||Non-union long-bone fractures||NCT01756326||Halted to focus on Allob in fractures|
|Allob||Phase II||Allob-RIF1||23||Rescue interbody fusion||NCT02328287||Halted to focus on Allob in lumbar fusion|
|Allob||Phase I/IIa||Allob-DU1||35||Delayed-union long-bone fractures||NCT02020590||Halted for efficacy|