Bone Therapeutics ahead of schedule in delayed fractures

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%.

All over

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 
Project  Status  Study  N Conditions  Trial   ID  Completion 
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

To contact the writer of this story email Elizabeth Cairns in London at elizabethc@epvantage.com or follow @LizVantage on Twitter

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