DUBLIN – Bone Therapeutics SA is calling an early halt to a phase I/IIa trial of its Allob allogeneic cell therapy in patients with slow-to-heal bone fractures following an interim analysis that showed the therapy exceeded expectations. After six months follow-up in the 16 patients studied to date, the trial's data and safety monitoring board recommended concluding the study on efficacy grounds.

The open-label study recruited patients with long-bone (leg or arm) delayed-union fractures – that is, breaks that had failed to heal within a three-to-seven month time frame. Each received at the fracture site a single infusion of Allob, which comprises ex-vivo-cultured bone marrow cells taken from a healthy adult donor. These differentiate, under defined conditions, into human osteoblastic (bone-forming) cells, which regenerate healthy bone tissue.

The study employed two primary efficacy measures, radiological healing as measured by CT scan and a global disease evaluation score, based on a validated questionnaire. Every patient hit at least one of those endpoints, defined as a minimum two-point improvement on the radiological Tomographic Union Score (TUS) or a 25 percent improvement on the Global Disease Evaluation (GDE) score. Thirteen of 16 patients hit the TUS endpoint – the average improvement across the study cohort was four points. Twelve of the 16 reached the GDE endpoint – the average improvement on that score was 48 percent.

The study was originally expected to recruit 32 patients. Six more received therapy before the six-month cut-off, and data from those as well as the first 16 participants will now be analyzed in full, Thomas Lienard, CEO of Gosselies, Belgium-based Bone Therapeutics, told BioWorld.

In parallel, the company will start drawing up plans for a phase IIb trial, in which Allob will be compared with "something else," Lienard said. "That 'something else' needs to be defined," he added. "Standard of care is wait and see."

Allob is not facing much in the way of incumbent competition. "There is very little innovation in orthopedics, apart from materials," he said. The only other option is a repeat surgical procedure.

The main safety finding in the trial was the development of a hypersensitivity reaction in one patient. "It was reported four weeks after [Allob] administration. No cause has been identified," Lienard said.

Pain at the fracture site, a secondary endpoint, was reduced, on average, by 59 percent. That, too, was statistically significant. "This secondary endpoint is important as pain is the primary concern of patients on a daily basis," Hugo Solvet, analyst at Bryan Garnier & Co., wrote in an investor note. "It is even more important for the cost-effectiveness of the health care system, as delayed-union fractures are likely to evolve to non-union fractures, resulting in long-term administration of anti-inflammatory [agents] to patients," he noted.

The result has prompted the company to halt further recruitment in an ongoing phase IIb/III trial of an autologous version of the same cell therapy, Preob, in patients with non-union fractures. Those represent an even more severe category, with patients' only alternative being bone graft, a painful and invasive procedure.

"Our focus is on the allogeneic platform," Lienard said. The company will analyze the data that have been generated to date, but in large indications, the allogeneic therapy has greater commercial potential because of its lower cost of goods and easier logistics.

A phase III trial of Preob will continue in patients with osteonecrosis of the hip, however, given the rarity of that condition. An interim read-out should become available by the third quarter of next year. Allob is also undergoing an open-label phase I/IIa trial in spinal fusion. It reported positive interim data last week from the first 15 patients in the study. Recruitment will be completed in late 2017 or early 2018, and the study will then require another 12 months of follow-up.

The response from investors was ambivalent. After peaking at €9.55 (US$11.46) early Wednesday, shares in Bone Therapeutics (Brussels:BOTHE) closed at €8.87, down 1 percent on the previous day's close of €8.97.

The company has struggled to convince shareholders to stay the course. The company raised €32 million in an IPO priced at €16 per share in February 2015, but some investors opted to exit the stock once the lock-up expired. "Some of them just wanted to take their profit," Lienard said.

Its share price has been in decline since then – and the imminent prospect of a dilutive capital increase hasn't helped matters. The company exited the second quarter with €12.6 million cash on its balance sheet. "Our current runway extends into Q2 2018," Lienard said. The company needs to raise significant levels of cash before then.