Mixed blessing: thanks to better medical treatment, the death rate for heart attack and angina patients fell by a third over the two decades through 2004. But heart attack survivors often go on to develop congestive heart failure, a condition in which a weakened heart is unable to pump enough blood to the body's organs. In extreme cases patients' lungs and limbs fill up with water, making them feel as if they are drowning. The U.S. spent $37 billion treating congestive heart failure last year.
The drugs for heart failure work, but only for a subset of patients. As many as 30% of patients who take beta blockers or angiotensin-converting enzyme inhibitors die, and another 40% are readmitted to the hospital within six months. "The mortality rate remains terrible," says Bertram Pitt, a cardiologist at the University of Michigan. "There is a great need for new approaches."
Big pharma's new drugs for heart failure have been disappointing.
In a midstage safety study of 94 heart failure patients with coronary artery disease and angina, all 65 patients treated with omecamtiv were able to safely walk on a treadmill. For many heart patients even a minimal amount of activity causes shortness of breath and chest pain.
Omecamtiv is intended for higher-risk heart failure patients in stable condition. The drug, given either in intravenous or oral form, works by activating a protein called cardiac myosin. Myosin is responsible for converting chemical energy into mechanical force, enabling heart muscle contraction. Existing drugs called positive inotropes speed up muscle contraction by increasing the amount of calcium inside muscle cells. The increased rate of muscle contraction, however, has been linked to dangerous side effects and death.
Omecamtiv is designed to make each heart contraction more efficient, not faster. The drug binds to myosin and triggers it to grab on and stay attached to a long string of proteins called actin. This interaction enables the heart muscle to contract for a longer period of time. "Think of it as putting more hands on a rope," says Andrew Wolff, a cardiologist and Cytokinetics' chief medical officer. Data from a midstage trial of 45 patients taking omecamtiv showed a 10% increase in the volume of blood their hearts pumped with every beat.
Biotech giant
Cytokinetics was formed in 1998 by four academic researchers working on different aspects of cell biology. Two were at Stanford, one at uc, San Francisco and another at UC, San Diego. Early on they held planning meetings in the red carpet lounge at the San Francisco International Airport. The company began by pursuing cancer drugs--targeting a protein that enabled cancer cell division. The promise of stopping cancer in its tracks helped Cytokinetics go public in 2004. However, progress on the cardiac muscle front soon eclipsed the company's cancer work, which included a couple of failed clinical trials. That, and the spiraling costs of conducting clinical trials in oncology, led Blum to pull the plug on cancer research in 2008. Last year Cytokinetics and GlaxoSmithkline agreed to end a partnership in the same area.
Blum has grand plans to apply his researchers' knowledge of the cytoskeleton--and the lessons from the $400 million the company has spent thus far--to an array of other diseases in which muscles are weakened. Midstage trials on a drug to treat amyotrophic lateral sclerosis (Lou Gehrig's disease) will start this spring. Other targets on Blum's radar screen include asthma, hypertension and coronary obstructive pulmonary disease.
