At the beginning of last month Abbott stopped selling its pioneering bioresorbable drug-eluting vascular scaffold, Absorb, saying the device had just not taken off. Undeterred by Absorb’s woeful reception by the market, the private group Amaranth Medical wants to get its first dissolving scaffold CE-marked by the end of the year. And the company believes that tweaking a single design aspect is key to cracking the market.
“Reduction of the strut thickness is a significantly important feature for these devices,” says Kamal Ramzipoor, Amaranth’s chief executive. “We need to be approaching the boundaries of best-in-class metallic drug-eluting stents – unless you do that we believe it’s going to be very difficult for these devices to have any kind of market traction.”
The drug-eluting stent (DES) generally acknowledged as the best, and certainly the market leader, is Abbott’s Xience V, whose cobalt chromium framework has a strut thickness of 81μm. The struts of Absorb, made of polylactic acid, are nearly twice as thick at 156μm.
The size of the struts is important as it affects the mechanical properties of the device, including strength and flexibility.
“Metallic DESs have set the bar high as far as their mechanical properties are concerned, especially their ability to expand and make sure that the stent is fully apposed against the vessel wall,” Mr Ramzipoor says. Absorb, he suggests, did not have sufficient radial strength or expansion capacity. “A combination of those two factors caused a significant amount of stagnation of the blood, and stagnation causes thrombosis.”
Amaranth, he says, has solved these issues. The company has developed a way of manufacturing an ultra-high molecular weight polylactic acid structure that is much thinner than Absorb’s without sacrificing strength. It has been a stepwise process: the company has come up with three devices, each with spindlier struts than the last.
The first device, Fortitude, has struts that are barely thinner than Absorb’s, at 150μm. Data presented at last year’s Transcatheter Cardiovascular Therapeutics meeting showed a 4.9% target vessel failure (TVF) rate – two of the three events were peri-procedural heart attacks – in 63 patients. Average late loss, a measure of efficacy, was 0.27mm at nine months.
In Absorb’s pivotal US trial in 2,000 patients the rate of the primary endpoint, a similar measure called target lesion failure, was 7.8% at one year (Absorb data could allow Abbott to retain stent leadership, October 13, 2015). This is not directly comparable, of course.
In any case Fortitude will not be going to market. Instead Amaranth is prioritising its Aptitude device, which has struts 115μm thick and posted a nine-month TVF rate of 3.4% in its 60-patient European approval trial, Renascent-II. The study’s other primary endpoint, in-scaffold late lumen loss, was 0.19mm – better than Fortitude’s.
Amaranth expects Aptitude to be CE-marked in December, Mr Ramzipoor says. Here it will face competition from the other drug-coated bioresorbable scaffolds in Europe, those sold by Biotronik, Reva Medical and Elixir Medical. The first two have struts only marginally thicker than Aptitude’s.
|Strut thickness of selected bioresorbable scaffolds|
|Company||Device||Status||Strut thickness (μm)||Material||Time to bioresorption (approx)||Drug|
|Abbott||Xience V (metallic DES)||Approved worldwide||81||Cobalt chromium||N/A||Everolimus|
|Amaranth||Magnitude||CE mark expected in March 2018||98||Polylactic acid||Not disclosed||Sirolimus|
|Meril Life Science||MeRes 100||R&D||100||Polylactic acid||Not disclosed||Sirolimus|
|Amaranth||Aptitude||CE mark expected in December||115||Polylactic acid||Not disclosed||Sirolimus|
|Biotronik||Magmaris||CE-marked June 15, 2016||120||Magnesium alloy||9 mth||Paclitaxel|
|Reva Medical||Fantom||CE-marked April 4, 2017||125||Desaminotyrosine polycarbonate||12 mth||Sirolimus|
|Elixir Medical||DESolve||CE-marked May 13, 2014||150||Polylactic acid||24–36 mth||Novolimus & myolimus|
|Abbott||Absorb||Withdrawn from sale worldwide||156||Polylactic acid||48 mth||Everolimus|
|Shandong Huaan Biotechnology||Xinsorb||R&D||160||Polylactic acid||Not disclosed||Sirolimus|
|Arterial Remodeling Technologies||Pure||CE-marked May 18, 2015||170||Polylactic acid||18–24 mth||No drug|
|Amaranth||Fortitude||Will not be taken to market||150||Polylactic acid||18 mth||Sirolimus|
|Source: EvaluateMedTech and company websites.|
“Look at the comparators; on strut thickness they are about 120-125 micron range, and it’s really unclear to us what their exact mechanical properties are,” says Mr Ramzipoor. “How do they compare to metallic DESs? Being 120-125 microns is a significant disadvantage.”
It is Amaranth’s third scaffold, however, to which the company has pinned most of its hopes. Magnitude has struts 98μm in diameter – the thinnest dissolving scaffold developed by any company so far.
The Renascent III study of Magnitude has just concluded, Mr Ramzipoor says, and nine-month clinical data will emerge “in the early part of next year”. CE mark will not be far behind, with Mr Ramzipoor saying he is confident of European approval in March.
Amaranth’s Magnitude scaffold
European trials will not stop then. Renascent II and III are single-arm studies, designed only to show the devices’ safety. Next year Amaranth will start a 500-patient head-to-head trial of Magnitude against Abbott’s Xience V, in a bid to convince cardiologists that its device is as good as or better than the market leader.
“The idea is we would have the best-in-class bioresorbable scaffold randomised against the best-in-class metallic DES,” Mr Ramzipoor says.
After that, the US beckons. Amaranth is conducting a financing round, and if the amount raised is sufficient – Mr Ramzipoor declines to name a figure – it will kick off a US registration trial in 2,000 patients, again pitting Magnitude against Xience.
The question of market reception looms large. Absorb’s pivotal US trial was a head-to-head against Xience too, and while it hit non-inferiority on the primary endpoint it was numerically weaker. Presumably doctors will be looking for a better showing by Magnitude than Absorb could muster.
Absorb was on sale in Europe for six years but lasted only 14 months in the US. Future clinical data – some will likely emerge at the TCT meeting in Denver next week – might give a suggestion of the potential of Amaranth’s technology, but the scaffolds can only be truly judged successful if sales are rather better than those of Absorb.
|Phase II trials of Amaranth's scaffolds|
|Device||Trial name||N||Completion||NCT ID|
|Fortitude||Mend II||42||Jun 2016||NCT02189499|
|Aptitude||Renascent II||60||Apr 2017||NCT02568462|
|Magnitude||Renascent III||70||Mar 2018||NCT02900937|