Coumadin has been used since the 1950's for the prevention of clots, and has been the best selling oral anticoagulant for a number of years. First developed as a rat poison, Coumadin works by inhibiting vitamin K dependent clotting factors II, VII, IX, and X as well as protein C and S. While Coumadin has saved countless lives it has a few severe limitations. First it interacts with a variety of foods and drugs which is problematic because it also has narrow therapeutic window. Because of these first two reason Coumadin requires monitoring to ensure the patient's dose it just right, this can be expensive and difficult for patients. Coumadin can also cause bleeding, necrosis, and osteoporosis. Recently numerous drug companies searching for their next blockbuster have invested millions to develop alternatives to Coumadin. Here are a breakdown of a few of the prime candidates.
-received priority approval which is restricted to drugs the FDA believes are major advances in treatment
-Both Pfizer (Lipitor) and BMS (Plavix) have experienced sales reps in the areas of cardiology
-the ARISTOTLE trial showed that patients suffering from Atrial Fibrillation have reduced risk of stroke and death while taking Eliquis compared to Coumadin, while also having a decreased bleeding risk
- Patients in the Coumadin arm of the ARISTOTLE trial were in correct therapeutic range more often then patients in the ROCKET AF trial
-twice daily which decreases patient compliance
- ADOPT trial showed that Eliquis was not superior to Lovonox when being used for thromboprophylaxis, while having a higher risk of bleeding
-APPRAISE trial showed that Eliquis was non beneficial in patients post ACS and increased their bleeding risk
-still not available in the United States, however might be approved by March
Johnson & Johnson, Bayer (OTCPK:BAYRY)
-approved for prophylaxis in hip and knee replacements and is already on some hospital formularies (however only given for a limited duration)
- taken once daily which increases compliance
-first oral direct factor Xa inhibitor available in the United States
- did not receive a priority review
- Study results for treating Atrial Fibrillation were not as impressive as Eliquis
- given a black box warning by the FDA
-patients taking Coumadin in the ROCKET AF trial were in the therapuetic range only 57.8% of the time
-the ROCKET AF trial only showed superiority to Coumadin when using the as treated safety population in their analysis
Pradaxa (Dabigatran Etexilate)
- first of the three to the market
- RE-LY trial showed that 110 mg dose decreased risk of hemorrhage while having comparable rates of stroke compared to Coumadin
-RE-LY trial showed that 150 mg dose decreased risk of stroke while having comparable rates of hemorrhage compared to Coumadin
- taken twice daily
- unreliable absorption
- study results were not as impressive as the Eliquis APPRAISE trial
Coumadin has been the standard of care for a long time despite a variety of shortcomings. While all these drugs are all a step up from Coumadin they do have a few weaknesses compared to Coumadin. First they will be considerably more expensive on a pill per pill basis. However unlike Coumadin they don't require monitoring which can be expensive and time consuming. Also Coumadin can be reversed using Vitamin K while none of these three currently have a proven and vetted reversal process. Finally all of these drugs have to be adjusted based on renal function while Coumadin does not.
Unfortunately it will be many years if ever before we see any head to head comparisons between these drugs. Therefore we are forced to speculate based on study results which medication is best for the patient and therefore will lead the market in sales. Personally I see Eliquis being the big winner among these three. The results of the ARISTOTLE trial really set it apart from the competition, combined with the sales experience of BMS and Pfizer should give Eliquis a huge advantage. Since BMS and Pfizer will split the revenues, and BMS has a market cap roughly one third that of Pfizer I think they stand the most to gain.
Disclosure: I am long PFE.