Osteonecrosis miss puts Bone Therapeutics on thin ice

The phase III failure of one of Bone Therapeutics’ cell therapies puts its other one under greater pressure than ever.

Last year Bone Therapeutics shelved one of its two trials of Preob, its autologous osteoblastic cell therapy, to focus on its donor-derived osteoblast therapy Allob, which it felt was more promising. The one trial of Preob that Bone had left to continue has now been halted early for futility, scything 27% off the Belgian group’s value. 

The group has one other asset, the viscosupplement JTA-004, which failed in a clinical trial last month – though notably Bone’s stock went up as a result of a successful post-hoc data dredge. One way and another, an awful lot is riding on Allob, and the phase II readout in spinal fusion that is due early next year could not be more crucial. 

The trial that came a cropper yesterday was a phase III study of Preob in patients with early-stage osteonecrosis of the femoral head. The project was implanted into the necrotic lesion in combination with core decompression, a common procedure for osteonecrosis in which the surgeon drills into the bone. A control group underwent core decompression along with the implantation of a placebo.

An interim analysis of the first 44 patients to hit 12 months of follow up prompted the trial's data and safety monitoring board to recommend that it be called off since it had little hope of success. 

Bone halted a phase II/III trial of Preob in non-union fractures just over a year ago, despite having funded five years’ work on that study alone (Bone Therapeutics ahead of schedule in delayed fractures, September 20, 2017). Instead it threw all its broken-bone efforts behind Allob, a trial of which in delayed-union fractures had been stopped early for efficacy. 

Now it looks like osteonecrosis is a dead end for Preob, and Bone has abandoned the product in favour of its allogeneic cousin, Allob. This is further from market than Preob, however, and Bone’s protestations that Allob is more osteogenic, more easily scalable and is intended for larger patient populations have not impressed investors hoping for a nearer-term revenue stream. 

Fusion data

Allob’s 32-patient phase IIa trial in lumbar spinal fusion is due to yield data in the middle of next year, and the group will need a smash hit if it wants to prevent its shareholders going from disappointed to enraged. Allob has shown promise in a second potential indication, delayed-union fractures; it was this that prompted last autumn’s refocusing away from Preob. 

But here, again, it will probably take at least two larger trials to get approval, and it will be the second half of 2019 before the group manages to even apply for a phase IIb trial in delayed union. Part of the reason for this long lead time is Bone’s decision to put a new manufacturing process in place for Allob – this is intended to improve scalability and cost effectiveness but necessitates further delays.

Reporting its third-quarter results today the group said it would run out of cash in the third quarter of next year. It will need to drum up funding somehow if it is to get Allob anywhere near the market.

Bone Therapeutics' clinical trials 
Project  Status  Study  N Conditions  Trial ID  Results
Allob  Phase IIa  Allob-IF1  32 Lumbar spinal fusion NCT02205138  Expected mid-2019
JTA-004 Phase II/III JTA-KOA1 229 Knee osteoarthritis NCT02740231 Failed; post-hoc subgroup hit
Preob  Phase III  Preob-ON3  118 Osteonecrosis of the hip NCT01529008  Halted for futility
Preob  Phase IIb/III  Preob-NU3  176  Non-union long-bone fractures  NCT01756326  Halted to focus on Allob
Allob  Phase II  Allob-RIF1  23 Rescue interbody fusion  NCT02328287  Halted to focus on the lumbar fusion trial of Allob
Allob  Phase I/IIa  Allob-DU1  35  Delayed-union long-bone fractures  NCT02020590  Halted for efficacy
Source: EvaluatePharma, Clinicaltrials.gov.

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