Bone grafts that elute active substances have run into trouble in the past, but Swedish start-up Bonesupport seems to be on safer ground with its injectable bone scaffolds that deliver antibiotics to guard against infections during the healing process. At least that is the argument that has attracted its new investors, who have pumped $37m into the company.
The cash will go towards developing new grafts that elute different compounds – including those that can actively promote bone growth. “We’re trying to develop not only the osteoconductive side of our capability but to see whether we can develop an osteoinductive scaffold,” says Richard Davies, Bonesupport’s chief executive.
Currently, the group has three scaffolds that support the growth of the host bone but do not actually promote it. Cerament BVF is the basic filler, approved for treating bone voids caused by trauma, infection, disease or surgery in both Europe and the US.
In Europe Bonesupport sells the grafts itself, but it has signed up Zimmer Biomet as commercial partner for the US. According to Mr Davies, sales are “going very well”.
It also has two antibiotic-leaching scaffolds: Cerament G and Cerament V, eluting gentamicin and vancomycin, respectively. They are used to treat bone infections and also prophylactically, in patients at risk for developing an infection.
Antibiotics must be released into a bone void over time, Mr Davies says, to ensure the concentration stays high enough for long enough to kill all the bacteria and avoid contributing to antibiotic resistance. “If you just squirt an antibiotic in there you’ve got no idea how long it stays above that concentration,” he says.
Both Cerament G and Cerament V are CE marked and the company is about to start a 230-patient pivotal US trial, Fortify, for the former when used during surgical repair of open diaphyseal tibial fractures. If all goes well Cerament G could hit the US market in 2019, a major milestone for the company, Mr Davies says. According to Mr Davies no antibiotic-eluting bone scaffolds exist, so the product will have to gain premarket approval. After that the company will submit Cerament V via the 510(k) pathway, using G as the predicate.
The $37m it has brought in via a combination of equity and debt finance will go towards funding this study and also generating health economic data. In Europe Cerament G and Cerament V cost around €1,800 to treat a single site, Mr Davies says, and they are reimbursed, but further evidence of their cost-effectiveness would help increase their use.
The funding will also allow the development of four new grafts currently at the preclinical stage. Mr Davies will not disclose what molecules these grafts might release, but a statement by the company suggests the indications could include osteoporosis, cancer and pain.
Development of these will have to be phased owing to “a bandwidth issue”.
Instead the company wants to develop osteoinductive grafts – although there have been risks with this approach. Five years ago an osteoinductive bone graft under development by Medtronic was linked with an increased risk of cancer and was rejected for approval by the FDA. The Amplify filler contained recombinant human bone morphogenetic protein-2 (rhBMP-2) to spur bone growth.
Another Medtronic bone graft that contains rhBMP-2 in a lower concentration, Infuse, remains FDA-approved; it is indicated for spinal procedures. Sales of Infuse topped $700m last year, according to EvaluateMedTech’s consensus data.
Bonesupport will have to develop any future osteoinductive products with care. But if it can avoid safety signals it could exploit a growing market, and Mr Davies has no shortage of ambition.
“We want to remain an independent orthobiologics company,” he says, adding that “at some point in the future” the company might seek to acquire other technologies.
“You’ve got to split out the hardware side of the orthopaedics market versus what’s essentially bone regeneration,” Mr Davies says. “When you start to think about the biologic side there are quite a few companies out there that [we could acquire to] become big enough to become a meaningful player in that space.”
Even so, Sanofi, NuVasive and Wright Medical all have bioactive bone grafts of one sort or another – to say nothing of Medtronic. Bonesupport will have to do a lot of acquiring to match the other groups active in the orthobiologics space.