St. Jude Medical’s Amplatzer PFO Occluder has finally returned to the US market after a decade in the wilderness. The device, used to plug a hole in the heart and thereby prevent recurrent stroke, has been approved by the FDA despite a failure in its pivotal trial.
The FDA appears to believe that the device is safe and effective when used in the right patients, saying that patients need to be evaluated by a neurologist and a cardiologist to rule out other causes of stroke. This careful choice of patients could limit the target US population to around 70,000 per year, but analysts suggest that half of these might be put off by the risk of adverse events. This is a win for St. Jude, and its acquirer Abbott, but will only be an incremental addition to revenues.
A patent foramen ovale (PFO) is a small hole in the wall between the right and left atria. It is possible for blood clots to pass through this and reach the brain, causing an ischaemic stroke. The catheter-mounted Amplatzer PFO Occluder is inserted via the femoral vein in the leg and deployed to block the hole.
Tales from the crypt
There is no definitive link between PFO and stroke. However, PFOs are present in around 40% of cryptogenic stroke patients – those whose stroke has no known cause – compared with 25% of people in the general population or non-cryptogenic stroke patients.
In its pivotal trial, Respect, in which nine of 499 patients treated with the Amplatzer (1.6%) had a stroke compared with 16 of 481 (3%) given drug therapy. This 47% risk reduction did not meet statistical significance, with a p value of 0.157 (Tricky panel approaches for St. Jude, and therefore Abbott, May 9, 2016). Nonetheless it received a narrowly positive verdict from an FDA adcom.
It is unusual for a device to gain approval when it failed in its pivotal trial, though it is certainly true that in recent years the FDA has worked hard to try to speed new technologies to market.
Probably the main reason the agency gave this device the nod is that it is well aware that off-label treatment of PFO stroke with other transcatheter devices is relatively common – indeed, one of St. Jude’s own products, the Amplatzer Septal Occluder, has been used in this context. Approving the PFO Occluder allows the FDA to better regulate the field and inform patients of the risks and benefits.
Analysts from Wells Fargo wrote that around 70,000 patients would be eligible for treatment with St. Jude’s device each year. However, “given the potential for serious adverse events with the procedure,” the peak penetration rate would likely be below 50%, they wrote. At around $5,000 per device this could mean annual US sales of less than $200m.
And bearing in mind St Jude was already seeing a small number of sales in PFO thanks to off-label use of other devices, this figure will be even smaller. Still, every little helps, and the PFO Occluder has the rare distinction of defying its trial data to gain approval.