Since the introduction of the classic anticoagulant agents, heparin (bovine and porcine heparin) and vitamin K antagonists (dicoumarol and warfarin), in the late 1930’s and early 1940’s, respectively, there were no NME drug approvals in this therapeutic class until the early 1990’s, with the introduction of two new pharmacologic classes, P2Y12 platelet inhibitors and low molecular weight heparins. This was followed by the introduction of two additional pharmacologic classes in the early 2010’s, factor IIx or Xa inhibitors and PAR-1 platelet inhibitors. The number of approved NME’s belonging to these four pharmacologic classes (click on drugs for Thrombosis) and the number of years over which these new drugs were approved, are as follows:
- P2Y12 Platelet Inhibitors: 4 NME’s; over 19 years and 9 months; 1991-2011. Note Ticlid (ticlopidine) has been discontinued
- Low Molecular Weight Heparins: 5 NME’s, over 8 years and 8 months; 1993-2001. Note Normiflow (ardeparin) has been taken off the market
- Factor IIx and Xa Inhibitors: 4 NME’s, over 4 years and 2 months; 2010-2015. Note Pradaxa (dabigatran) is a Factor IIx inhibitor; the others are Factor Xa inhibitors, and
- PAR-1 Platelet Inhibitors: 1 NME; 2014
Note this listing does not include the antiplatelet agent aspirin (listed here with the older drugs) or the thrombolytic agents streptokinase and later plasminogen activators.
What is noteworthy about this therapeutic class is: 1) since 1991 there has been a reasonably steady introduction of new antithrombotic agents, involving four new pharmacologic classes. Three of these pharmacologic classes have involved 4-5 approvals each, which is a common number of approved drugs per pharmacologic class (see pages 34 and 36 in the 2014 Report), and the same three pharmacologic classes had approvals over 4 to 19 years each, which is a common number of years of registration activity (see pages 35 and 36 in the 2014 Report); and 2) preceding this particular time period (early 1990’s to present) by one to two decades, there had been significant scientific advances in our understanding of the pharmacology of antithrombotic agents, including the identification of the active sequence in standard heparin, leading to LMWH’s, and the identification of efficacious new non-cyclooxygenase inhibitor-dependent antiplatelet mechanisms, as exemplified by Plavix (clopidogrel) and Zontivity (vorapaxar). Based on these developments, and looking at what’s been typical for other pharmacologic and therapeutic classes, one wonders what’s next? Will there be other approvals in the three pharmacologic classes where there have already been 4-5 approvals, and if so, how many? If not, what then?
Refer to page 10 of Progression of Modern Therapeutics (2014 Report) available under Reports on this website; this report also includes the methodology used.