A look at emerging medications and treatments likely to receive notice in 2009.
Keep an eye on key therapeutic areas in 2009, as new drugs go through the FDA pipeline. Key areas are cardiovascular disorders, central nervous system (CNS) disorders, respiratory disease, and diabetes, reported Brian W. Kolling, PharmD, at the recent Academy of Managed Care Pharmacy meeting in Kansas City, Mo.
According to Keith Bradbury, executive director of drug information at Medco Health Solutions Inc., the FDA has delayed approval of many new drug applications (NDAs) as the agency struggles with implementing new regulations established by the 2007 FDA Amendment Act.
"We are at a historic time in terms of the number of products the FDA has delayed or allowed the user end-date to pass and extended the review period," Bradbury said.
According to Bradbury, a home run might occur in the cardiovascular field. Bradbury was referring to rivaroxaban (Xarelto; Bayer/J&J); if approved, it will be the first new oral anticoagulant to reach the market in more than 40 years. "This is potentially a multibillion-dollar drug. It looks very promising," Bradbury said.
Another cardiovascular agent is prasugrel (Effient; Lilly). "The $64,000 question: 'Is the FDA going to be able to tease out from the data whether the drug is in the net beneficial and not harmful?' If this happens, then [clopidogrel (Plavix; Sanofi-Aventis/Bristol Meyers Squibb)] is going to have some ... competition," Bradbury said.
Generic products will continue to make inroads into the cardiovascular market as the top-selling statin, angiotensin II receptor blocker (ARB), and antiplatelet drug all go off patent by 2012. There is also a full field of factor Xa inhibitors, with more than nine new products in the pipeline, two of which are now in phase 3 trials.
Statins will still dominate cholesterol management, but combination products and several agents with new mechanisms of action are making their way through the approval process. New products to watch for include GlaxoSmith-Kline's darapladib, which targets lipoprotein-associated phospholipase (Lp-PLA2), and Isis and Genzyme's mipomersen, an apolipoprotein ±00 antisense inhibitor designed as a lipid reducer for high-risk cardiovascular patients. Two new cholesteryl ester transfer protein (CETP) inhibitors, Merck's anacetrapib and Roche's R1658, are also on the horizon.
There has been a push to develop new antiplatelet and antithrombotic agents to replace less effective and more costly products. As mentioned previously, if approved, prasugrel, a platelet inhibitor used for the prevention of cardiovascular events in patients with acute coronary syndrome (ACS), could rival clopidogrel, which is set to see its patent expire in 2011. However, if the FDA requires additional clinical trials to study bleeding issues that have been raised with these drugs, prasugrel's approval might be delayed.
With possible approval in 2010 or 2011, TRA-SCH-530 -348 (Schering-Plough), an oral antiplatelet drug, would be the first in a new class of thrombin-receptor antagonists. TRA-SCH-530348 prevents blood clots by inhibiting thrombin action.
Another new antiplatelet formulation is AZD6140, the first reversible oral adenosine diphosphate (ADP) receptor antagonist. Developed to reduce the risk of thrombotic events in ACS patients, AZD6140 inhibits platelet aggregation. Clinical benefits of reversibility are unclear; however, trials now under way may shed light on the issue.
With limited clinical choices for the prevention of thromboembolic disease, two anticoagulants could meet the need for new products in this area: once-daily dosage of rivaroxaban, being studied for prevention of venous blood clots in elective hip- or knee-replacement surgery, and dabigatran etexilate (Boehringer Ingelheim), an oral reversible direct thrombin inhibitor. Rivaroxaban, a direct Xa inhibitor, is expected to enter phase 3 trials for ACS in mid-2009; venous thromboembolism (VTE) prevention launch is estimated for later this year. Trials of dabigatran for acute VTE and secondary prevention of VTE, and prevention of cardiovascular events in ACE, are ongoing.
Dronedarone (Multaq; Sanofi-Aventis), a multichannel blocker with anti-adrenergic properties that is chemically similar to amiodarone, is being studied in patients with atrial fibrillation or atrial flutter. Clinical trial results indicate that this agent may be better tolerated than amiodarone.