The leader of a market has the furthest to fall. Abbott, on top of the drug-eluting stent sector for some years now thanks to its blockbuster Xience device, knows that sales of its workhorse will decline in the coming years and has pioneered bioresorbable technology in a bid to fill the gap.
Yesterday’s positive – with caveats – pivotal trial read-out for Absorb puts the drug-coated dissolving scaffold on track for US approval next year and ought to ensure that Abbott remains the top drug-eluting stent (DES) seller in 2020 (see table below). Much depends on doctors’ willingness to use this unfamiliar technology and on pricing and reimbursement, but with none of the big players likely to be able to match this achievement for some years to come, Abbott’s bet on innovation looks to have paid off.
The 2,000-patient Absorb III study met its primary endpoint, with the new scaffold showing non-inferiority to Xience on the measure of target lesion failure (TLF) at one year, according to data presented at the Transcatheter Cardiovascular Therapies conference in San Francisco.
TLF was defined as a composite of cardiac death and heart attack attributable to the target vessel and repeat procedures within the treated lesion caused by ischaemia; the margin for non-inferiority was 4.5 percentage points for risk difference.
Though Absorb met the criteria for non-inferiority on the TLF measure with a p value of less than 0.007 – the event occurred in 7.8% of Absorb patients compared with 6.1% of patients given Xience – on this endpoint and several others it was numerically weaker.
There were no statistically significant differences between Absorb and the control on any of the secondary endpoints – but one red flag did emerge in the one-year rates of in-stent thrombosis.
At 1.5% for Absorb and 0.7% for Xience in the intent-to-treat group, this difference was not statistically significant, at p=0.13, but the rate of subacute device thrombosis – that occurring between 24 hours and 30 days after the procedure – was significantly higher in the Absorb group. In the as-treated cohort, though, thrombosis rates did not differ significantly between the devices during any interval.
This is a concern because much of the rationale for bioresorbable stents is that their elimination from the body does away with device thrombosis, among other adverse events, at a much later stage. If using Absorb in preference to Xience means that patients are merely swapping very late thrombosis for clots during the subacute period, the appeal of the device wanes.
There are other pros and cons of the Absorb III trial: on one hand, for instance, the patients in the study were probably easier to treat than those likely to be encountered in real-life practice; on the other, Xience is the right comparator, being not only the bestseller but generally acknowledged as the gold standard among DESs.
Be that as it may, the primary endpoint was met and the data are almost certainly good enough for approval. One of only two dissolving scaffolds on sale in Europe, Absorb will have the US market for itself for some years yet.
The other CE marked product is Elixir Medical’s DESolve, which reached Europe around two years after Absorb (CE mark for dissolving stent pits Elixir against Abbott, June 10, 2013). DESolve is not in any US clinical trials according to clinicaltrials.gov; whether a relatively small private company could afford to run a US approval trial is open to question.
Biotronik is also developing an absorbable stent, which unlike Absorb and DESolve, is made of metal. Data from the first human trial of the Dreams 2G device were also presented at TCT, and while these were positive this magnesium alloy scaffold is unlikely to reach market within the year.
|Drug-eluting stents - the billion-dollar sellers|
|Global sales ($m)|
|Abbott Laboratories||Drug-eluting stents/ bioresorbable vascular scaffolds total||1,463||1,484||+0%|
|Boston Scientific||Taxus and Taxus Element||81||45||-9%|
|Boston Scientific||Promus and Promus Element||970||660||-6%|
|Boston Scientific||Other drug-eluting stents||18||100||+33%|
|Boston Scientific||Drug-eluting coronary stents total||1,151||1,226||+1%|
|Medtronic||Endeavor/Resolute - total||1,068||968||-2%|
Absorb’s chances of taking off in the US are heavily dependent on whether interventional cardiologists see the potential advantages of Absorb as worth switching to a new device, and one that is harder to implant than metallic DESs.
If it does sell well it is not inconceivable that the other two players here, Medtronic and Boston Scientific, will want a piece of the action. Boston is in early trials with a bioresorbable scaffold and has also formed agreements with other smaller groups with similar technologies.
Medtronic, however, is not known to have made any concrete efforts in this space. With its DES sales forecast to drop 2% to the wrong side of the billion-dollar mark in 2020, and having shown itself to have an almost insatiable appetite for tuck-in acquisitions, a match-up between Medtronic and Elixir Medical or Biotronik would turn an interesting technological development into the next interventional cardiology battleground.