Since July Invivo Therapeutics has insisted that the three patient deaths in Inspire, the pivotal trial of its spine graft, were unrelated to the treatment itself. This might well be the case, but the company has shelved the trial and will be starting another – despite Inspire meeting its primary endpoint.
The decision appalled the few investors who had stuck around in the hope that Inspire would be re-started after its halting in July and still form the basis of a US approval. Invivo’s shares slumped 21% yesterday, crowning a year in which the stock fell 84% and raising the question of how exactly the company, which has no revenue stream, plans to fund the new study.
Invivo has already taken a chainsaw to its workforce – metaphorically – saying in late August that it would cut its headcount by nearly 40% to save money. Other cost-saving measures include putting enrolment into a Canadian trial of the same spinal graft on hiatus and halting its separate stem cell and gene therapy programmes.
The graft, known as Neuro-Spinal Scaffold, is a bioresorbable polymer mixture implanted at the site of a spinal cord injury. It is intended to allow the patient’s neural tissue to regrow as the scaffold is resorbed.
16 of 19 patients in Inspire were available for follow-up at six months, and seven had an improvement from baseline of at least one grade on the American Spinal Injury Association impairment scale. This surpassed the figure defining the success of the trial, 25%. This threshold was based on spontaneous recovery rates seen in this patient population – around 15% of patients would be expected to improve by one grade or more at six months with no intervention.
The other three patients enrolled died within two weeks of implantation. The third death prompted recruitment in the trial to be halted; at the time Invivo said it would resume enrolment in the first half of 2018, and file for a humanitarian device exemption (HDE) with the FDA in the second half (Third trial death endangers Invivo, August 1, 2017).
This timeline will of course lapse if the proposed new trial of Neuro-Spinal Scaffold goes ahead. The company is proposing a randomised controlled study, which might seem unnecessarily risky – after all, the FDA previously agreed that the uncontrolled Inspire would be sufficient for approval.
However, approval under an HDE simply does not require a product to prove efficacy better than placebo. What Invivo likely wants to show in the new trial is that patients in the control arm, which will presumably involve some sort of sham procedure, die at roughly the same rates as those who receive the scaffold.
Still, with Inspire showing a 37% success rate (seven of 19 patients) versus a 16% death rate (three of 19 patients) the graft will have to put in a better performance in the new study – if not for approval, then to convince doctors and payers.
And before it gets to that point there remains the problem of paying for the trial. Invivo, which is pre-revenue, had cash reserves of $16.4m at the end of September, which it said would be sufficient to fund operations into the third quarter of 2018.
Yesterday it said it was exploring “various strategic and financing options” for the development of Neuro-Spinal Scaffold. This will be the first of many impediments Invivo and its product will have to overcome.