When medtech companies seek to address stroke they often aim at either prevention or the acute phase of treatment, with devices to either catch clots or break them up. Helsinki’s Nexstim is an exception, looking at the post-acute phase with a system that induces an electrical field in the brain to boost the effect of physiotherapy. With phase II data and an IPO under its belt, the company will soon see the result of an interim look at its pivotal US trial.
“We have an 84% response rate, which is huge in rehab, and this is three months post-onset of stroke so all the normal healing process is already done,” Janne Huhtala, the company’s chief executive, tells EP Vantage. But the Navigated Brain Therapy (NBT) system is expensive, and the company will have to tread carefully on pricing if it is to get past the gatekeepers of rehab clinics.
The NBT system uses transcranial magnetic stimulation to generate a precisely targeted electric field within the brain. This field does not stimulate neural activity in the damaged part of the brain, but attenuates it – and in the part of the brain directly opposite the lesion.
The idea is that by temporarily dialling down the healthy side of the brain, which would usually simply take over from the damaged part, the nerves in the site affected by the stroke have room to improve. The procedure takes around 17 minutes and is performed immediately before a physiotherapy session; the healthy tissue recovers within an hour or so, Mr Huhtala says.
And the damaged tissue recovers too, although over a longer time frame. At least this is what the phase I/II ContraStim study showed, with 16 of the 19 treated patients reaching the minimal clinical important difference on the Upper Extremity Fugl Meyer scale six months after treatment.
The 84% response rate was “unheard of”, says Mr Huhtala. It was significantly greater than that seen in the 10-patient sham treatment group, with a p value of 0.05. The Fugl Meyer scale is a measure of motor function recovery; treatment with the NBT system led to an absolute improvement of 13.8 points, which Nexstim says is the difference between being able to grasp an object and button a shirt.
Dream come true
The group must now replicate these effects in its much larger phase III study called Niche, which it began last spring. This will enrol 200 patients very similar to those in ContraStim – having had an ischaemic or haemorrhagic stroke on one side of the brain, resulting in upper extremity paresis, 3-12 months prior to the study.
An interim analysis of the first 81 patients will be conducted in the next quarter. “The DSMB will review the data and say whether we can meet the endpoint already, or whether there are any safety issues,” says Mr Huhtala.
A win on efficacy at this early stage would be “almost like a dream come true”, he says, though he does add that the company is not expecting that. Neither is it expecting any safety issues, and given that the worst adverse event seen with the NBT so far is a transient headache, this seems fair enough.
Assuming Nexstim is advised to continue the trial, a second interim look at 138 patients will occur in the first quarter of next year, and final results in Q3 2016. Even if the interim analyses are positive, Mr Huhtala says the company will continue trial until all 200 patients are treated; there are few trials in stroke rehab this big, and the full dataset will be useful for marketing purposes.
The device will be regulated via the de novo path in the US. It can avoid the longer, more costly PMA route as the FDA considers it low-risk; but with nothing like it already approved it has no predicate that would permit it a straightforward 510(k) clearance.
In fact, a very similar Nexstim device using much of the same technology is already approved in the US and Europe for diagnostic purposes: it can noninvasively map areas of the brain controlling muscle movements prior to brain surgery. Previously this either necessitated craniotomy or could be done with fMRI – though this measures blood flow as a proxy for brain function.
Sales for this use are, however, negligible – though the fact that the system has been used for this purpose without raising safety flags is certainly helpful. Stroke rehab is the main opportunity, and here pricing will have to be carefully considered.
The market for a post-acute stroke therapy could be huge, Mr Huhtala says. The US spends $8.5bn a year on post-stroke rehab, he says, “but it doesn’t help the patients really", and Nexstim’s target market is worth $1.8bn.
Even with this kind of money sloshing about the company will have to work to persuade payers. As a diagnostic technology the device costs about $250,000, but Mr Huhtala says that is too expensive for the rehab setting.
So Nexstim will lower the price of the NBT system, though the final pricing here will depend on the results of the phase III clinical trial. It will use a razor/razorblade model, charging slightly more for consumables – single-use head trackers containing RFID tags that allow correct alignment of the system.
“It’s good for the rehab clinics,” Mr Huhtala says. “They like it because it’s risk sharing – they don’t have to pay for a device that they don’t know how much they’re going to use. We wanted to lower the threshold of starting.”
Nevertheless the technology will only really take off if payers believe that it can save money in the long term; stroke improvement must be stark and durable.
Unless and until the company starts booking sales – this could be as soon as 2017 and earlier than that if Niche is stopped early – it will need other sources of funding. Nexstim completed an IPO last year with a dual listing in Helsinki and Stockholm, raising €15.3m, but Mr Huhtala says the company will probably arrange further financing as it gears up for launch.
That said, the company would not reject a takeover offer out of hand. “We are always open for M&A. We have been owned by VC funds since we started, and their target is obvious: they want an exit,” Mr Huhtala says.
It seems likely that a potential buyer would want a slam-dunk on efficacy in Niche – the kind of results that will make the NBT system indispensable for rehab centres. They will doubtless pay close attention to the findings of the coming interim analysis.
|Trials of Nexstim's NBT in post-acute stroke treatment|
|ContraStim||Sham-controlled phase I/II in 20 patients||NCT01049802|
|Niche||Sham-controlled phase III in 200 patients; interim analysis Q3 15, full results Q3 16||NCT02089464|