Pharma companies in R&D battle as warfarin goes on

According to new research, approximately 8.5 million people suffer from chronic atrial fibrillation (AF) globally, and as many as 7% of AF patients will experience a stroke within the course of only one year. However, only 35% of patients who are candidates for treatment with the antithrombotic warfarin actually receive it despite convincing evidence of the drug's efficacy.  

The number of people in the seven major pharmaceutical markets who contract diseases caused by clotting are staggering - each year approximately 1.6 million people suffer heart attacks and 1.5 million are afflicted by a stroke. AF is the most common clinically significant form of cardiac arrhythmia, and increases the risk of stroke approximately five-fold.  

Keeping the blow flowing 

Antithrombotics keep the blood from forming clots and the patient potential for antithrombotic therapies is considerable as it covers a wide spectrum of diseases that range from deep vein thrombosis and pulmonary embolism to heart attacks and ischemic strokes. However, there is significant overlap between these patient groups and there is no such thing as one all-encompassing antithrombotics indication.  

Given the size of the patient pool and the often chronic nature of treatment, the promise of blockbuster revenue looms large and attracts almost all major pharmaceutical companies.  

However, beating the kings of the respective markets is not easy, and if you strike at a king you have to kill it. This is why 'me-too's' simply will not do and in order to protect the large amount of revenue that is derived from established brands, the market leaders are rapidly rolling out additional indications and conducting dose-optimization studies. These two life cycle management strategies are likely to complicate the market entry of novel antithrombotics as they impact the competitive landscape greatly by changing the comparator profile and confronting market entrants with competition even in niche sectors. 

The power of three 

Antithrombotic drugs comprise three classes: anticoagulants, antiplatelets and thrombolytics. Datamonitor estimates the total revenue generated from new antithrombotics will reach approximately $10 billion globally by 2015, with novel oral anticoagulants contributing over 70% to this volume.  

Furthermore, among developmental antithrombotics, only drugs in the antiplatelet and anticoagulant classes appear to have blockbuster potential, while new thrombolytic agents are unlikely to achieve high sales. Developmental thrombolytics hold little commercial promise because of established competitors, niche-focused launching strategies and the overall decline of the thrombolytics market that is driven by the increase in cardiovascular surgery. 

Currently, warfarin (sold as Coumadin by Bristol-Myers Squibb) and Sanofi-Aventis's Plavix (clopidogrel) are the two best-selling antithrombotics.  

Dosing difficulties 

Warfarin, an oral anticoagulant, was launched as Coumadin in the US in the 1940s by DuPont (now Bristol-Myers Squibb). Having come off patent decades ago, warfarin is also one of the cheapest drugs on the market costing less than 50 cents per tablet.  

However, finding the correct warfarin dose regimen is a difficult exercise. As there are considerable drug-drug and drug-food interactions, patients receiving warfarin require weekly monitoring as outpatients. Moreover, the lack of experience on the part of both patients and physicians in the initiation and maintenance of warfarin therapy carries the serious risks of inappropriate dosing. 

Any failure in dosing warfarin properly is likely to result either in over-anticoagulation (associated with increased risk of hemorrhage or internal bleeding) or under-anticoagulation (associated with increased risk of thrombosis or clotting and the prolonged need for parenteral anticoagulants). To avoid either under or over-dosing, physicians are reluctant to prescribe oral anticoagulants for the elderly, who are at the greatest risk of stroke and would likely benefit the most from prophylactic anticoagulation. 

Despite difficulties with the dosing regimen, warfarin and its derivatives remain the mainstay of oral anticoagulant therapy for the prevention of thromboembolic events in stroke, myocardial infarctions (heart attacks) and AF. Even taking into account the low price, its shortcomings and severe under-prescribing, warfarin and its derivatives still generated revenue of $700 million in 2004 alone. 

Because of the potential rewards on offer, replacing warfarin is viewed by some as the holy grail for pharmaceutical companies. Any novel oral anticoagulant that tackles warfarin's dosing shortcomings will capture the market and physicians are eagerly awaiting the launch of such a drug. The unmet need for it is so high that such an agent would be able to command a premium price. 

Following the demise of AstraZeneca's anticoagulant Exanta, Boehringer Ingelheim's BIBR-1048 and Bayer's BAY-597939 are next in line with a chance to switch warfarin-treated patients and grow the market by recruiting those patients currently going untreated.  

After the recent release of strong phase II data, BAY-597939 is the drug most likely to meet the market's demands for a safe and efficacious alternative to warfarin and therefore emerges as the most commercially successful with sales of $4.9 billion forecast by 2015.  

Taking on Plavix 

In the antiplatelet market, Bristol-Myers Squibb/Sanofi-Aventis's Plavix (clopidogrel) is the currently the undisputed gold-standard, accruing sales revenue of approximately $4.5 billion globally in 2004. However, clopidogrel's key weakness is its low efficacy, leaving the door ajar for potential market entrants.  

Datamonitor has identified at least one drug that is likely to take Plavix's crown as king of the market, namely Eli Lilly/Sankyo's prasugrel. Forecast to achieve sales of $1.5 billion by 2015, prasugrel has blockbuster potential and will take patient share from clopidogrel because it inhibits platelet aggregation to a higher and tighter degree.  

While the current medications available are adequate, they both have significant shortcomings; clopidogrel's lack of efficacy and the incredible difficulty in safely administering warfarin and the low quality of life that this engenders. However, these problems may bring about a significant upside. Because of the aforementioned problems with warfarin and clopidogrel, respectively, the market is essentially wide open for a pharmaceutical manufacturer that can produce drugs that improve on their standard of treatment. 

With such a potentially huge patient population, any such company that can fill this void will undoubtedly reap significant financial rewards. Because of this large financial carrot there is considerable R&D investment in this area, which greatly increases the chances of new and improved medications hitting the market sooner rather than later. 

Related research: 

• Pipeline Insight: Antithrombotics - Anticoagulants and Antiplatelets Have Blockbuster Potential priced $11,400
• Commercial Insight: Antithrombotics - Sanofi-Aventis the Dominant Player priced $15,200
• Stakeholder Insight: Heart Failure - Pumping Up Therapy Will Prevent Failure priced $15,200

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