Abbott's bioresorbable stent meets primary endpoint, but NEJM editorial raises questions

Abbott's Absorb bioresorbable stent--Courtesy of Abbott

Abbott ($ABT) once again said at the TCT conference that its drug-eluting bioresorbable Absorb BVS is comparable, or noninferior, to its standard drug-eluting Xience stent, as it seeks FDA approval next year, which would make it the first company to sell a fully bioresorbable stent in the U.S.

Abbott has conducted several trials, all of which have found noninferiority to the standard of care, but an accompanying editorial in the New England Journal of Medicine says a more sophisticated analysis that goes beyond the topline results reveals some concerns.

Abbott pointed to the headline data, saying the difference between the two devices' performance on the primary endpoint of target lesion failure was statistically insignificant by a large margin. The Absorb had a target lesion failure rate of 7.8%, compared to 6.1% for the Xience. Target lesion failure is a composite of heart disease-related deaths, heart attacks related to the treated vessel and repeat procedures of the treated lesion. Abbott's Absorb had a target lesion failure rate of 7.8%, compared to 6.1% for the Xience.

In addition, the company said in a release that there was no statistically significant difference in performance on secondary endpoints, or the rate of definite/probable stent thrombosis (blood clot formation near the device).

"Results of the ABSORB III pivotal trial show that Absorb is comparable to the best-in-class metallic stent. However, because Absorb leaves nothing behind it may provide significant long-term benefits, such as a restored vessel in a natural state and renewed possibilities for people treated with Absorb," said Dr. Charles Simonton, chief medical officer of Abbott Vascular in a statement.

The New England Journal of Medicine published not only Abbott's latest study, but a critical editorial that pointed that although the differences in the data between Abbott and the Xience are not statistically significant, the point estimates (or reported numbers) have a consistent pattern: the Absorb's metric is worse.

"Although the trial was designed in consultation with regulatory authorities, the absolute risk difference between the devices that is considered to be clinically unimportant--the noninferiority margin--is large at 4.5 percentage points against a background rate of the primary outcome of 6.0% with the metallic stent. Most clinicians in everyday practice would not accept this degree of difference between two stents in their catheterization laboratories. This means that the clinical relevance of the finding of statistical noninferiority is open to question," the editorial says.

It also said the higher (but statistically similar) rates of definite or probable thrombosis "probably mandate the conduct of new trials in an attempt to define the most effective duration and intensity of dual antiplatelet therapy in patients receiving these devices," and claimed that implantation of the bioresorbable device is more challenging.

Clearly, Abbott is going to have to fight off doubts about switching to a third paradigm of stents, following the advent of bare-metal and then permanent drug-eluting stents.

The good news for Abbott is the company is the clear leader in the fully bioresorbable stent space. Other CE-marked competitors like Elixir's bioresorbable DESolve haven't gained much market share, and no other device in the category is anywhere near FDA approval. Biotronik is also in the space, and touted the results of its trial to earn a CE mark during the conference.

The real threat to the Absorb likely comes from fellow bigwigs Boston Scientific ($BSX) and, over the longer term, Medtronic ($MDT). They are taking alternative approaches to reducing the body's long-term exposure to polymer coatings, which can cause inflammation reactions that lead to complications such as restenosis.

Boston Scientific's FDA-approved partially bioresorbable Synergy has a bioresorbable coating, but a permanent metallic body. The coating reduces the length of the body's exposure to polymers, while avoiding some of the doubts around the durability of bioresobable technology, previously expressed by Global Data analyst Amendeep Sanghera to FierceMedicalDevices.

Meanwhile, Medtronic's early-stage Drug-Filled Stent is not bioresorbable, but has an alternative and novel drug delivery mechanism that enables it to eliminate the use of polymers all together. At TCT, the company described the first implants of the device during an Australian clinical trial.

Both devices forgo some of the benefits of fully bioresorbable stents however, such as those described by Dr. Simonton.

Abbott can point to strong adoption of the device abroad, especially in emerging markets. India is its largest market right now, accounting for slightly more than a third of its $132 million in 2014 global revenues.

GlobalData projects the BVS is to hit sales of $96.3 million by 2017 in the U.S., but that assumed an FDA approval in 2016.

An FDA rejection of a device that's been implanted in more than 125,000 people abroad since receiving a CE mark in 2011 would send shivers down the spine of industry. The topline numbers showing noninferiority make approval appear likely, but the FDA will consider the in-depth data, like that in the NEJM editorial.

Abbott should find recent comments made by Dr. Jeffrey Shuren (the head of FDA's device arm) at the AdvaMed conference reassuring. He said that the first iteration of a paradigm shifting device (such as a bioresorbable stent) is often a bit underwhelming, but its approval is often needed to ensure patients can benefit from subsequent improvements down the line.

- read the Abbott release | here's Biotronik's release
- here's the NEJM study | here's the criticial editorial

Special Report: Leaders emerge in the race for the first U.S. bioresorbable stent -Abbott's Absorb BVS leads the pack