Humacyte’s goal of getting its bioengineered blood vessels approved by 2017 as grafts for use in haemodialysis patients was always ambitious. Following positive phase II data and the start of a phase III trial it now looks as if this could happen in 2018 – slightly later, but not bad considering the innovative nature of the technology.
Approval is, of course, not certain. Though the phase II investigators wrote that the artificial vessels “seem to [be] safe and functional” the technology will face a tougher challenge in phase III, where it will go up against polymer grafts, the standard of care. At least funding will not be a problem: Humacyte raised a series B round in October worth $150m.
Humacyte’s grafts, called Humacyl, are made using using cultured cadaveric human aorta cells. The cells are grown in a bioreactor on a tube-shaped biodegradable scaffold, producing an extracellular matrix at the same time as the scaffold degrades. The cells themselves are then removed from the matrix to make it non-immunogenic (Humacyte’s lab-grown veins could reach the US in 2017, February 20, 2014).
The grafts are intended for patients with end-stage renal disease who undergo haemodialysis three times a week. The process requires large volumes of blood to be withdrawn and reinfused and repeated needle puncture can harm the patient’s veins and arteries. Some patients have a graft attached to their veins to make this process easier and less painful, but current grafts, made of polytetrafluoroethylene, are prone to thrombosis, infection or blockages.
Humacyl was tested in two phase II trials, one in 20 patients and one in 40, who were followed for an average of 16 months. Eight patients were removed from evaluation, including four who died while the vessel was still open – none of the deaths were attributable to the Humacyl vessel, and the mortality rate was consistent with the general population of haemodialysis patients – one who had a kidney transplant, and three who withdrew consent.
At six months, 63% of patients had primary patency – functional access until any type of intervention to maintain or restore openness – and 73% had primary assisted patency, where the vessel still functioned without thrombosis. Also at six months, 97% had secondary patency, functional access with or without interventional or surgical procedures to maintain or re-establish openness, until either final failure or until the vessel was abandoned.
At 12 months, 28% had primary patency, 38% had primary assisted patency and 89% had secondary patency.
There was of course no control group in the studies, but the investigators wrote in The Lancet that the secondary patency rates were higher than that reported in studies of polymer grafts, which were around 55–65% at one year.
There was only one infection that required resection of a segment of the vessel. At 1.3% per patient-year, this infection rate is lower than that reported with polymer grafts, the investigators wrote.
The Humacyl grafts were also found to be repopulated with host cells, and the investigators suggest that as a result they may have been more resistant to bacterial infection than synthetic grafts.
Now it is time for phase III. The new trial will be the largest study of any bioengineered vascular tissue, Humacyte says, enrolling 350 patients and pitting the technology directly against polymer. The study ought to conclude in July 2017, and if it is positive Humacyl could hit the market in early or mid 2018.
There will be questions to answer over production and pricing at that point. For the next year or so Humacyte can concentrate on the clinic.