Amgen’s (AMGN) PCSK9 inhibitor evolucumab (AMG145), when added to standard treatments, helped 86% of patients get their LDL cholesterol levels to a target of 100 mg/dl or below, compared with 16% of patients on standard treatments alone. If the FDA holds to its recent comments that it will not require additional outcome studies for PCSK9 inhibitors, it could reduce the cost and time to market for this new class of cholesterol-lowering drugs.
Amgen presented the findings of its OSLER phase 2 study on November 19, 2013 at the American Heart Association’s annual meeting. According to the American Heart Association, an estimated 71 million Americans have high cholesterol, which is considered a significant risk in heart attacks, strokes and other coronary diseases.
Statin drugs such as Pfizer’s (PFE) atorvastatin (Lipitor), Merck’s (MRK) simvastatin (Zocor), AstraZeneca’s (AZE) rosuvastatin (Crestor) and generic equivalents, block an enzyme called HMG-CoA reductase, which controls cholesterol production in the liver. When the liver senses that its HMG-CoA reductase levels are too low, the liver responds by creating a protein that leads to an increase in the production of LDL (low density lipoprotein, or “bad” cholesterol) receptors.
The liver helps to clear LDL from the body; however, in some patients, the PCSK9 protein inhibits the liver’s ability to clear LDL from the patient’s blood. Amgen’s Evolucumab (AMG145) inhibits the PCSK9 protein, enabling the liver to remove LDL more effectively.
The phase 2 OSLER study looked at 1,300 patients in four separate arms comparing standard of care (statin therapy or equivalent treatment) to a combination of standard of care and AMG145. The study allowed for medication adjustment following the initial 12-weeks of treatment. The primary endpoint of this study was reduction in LDL for patients receiving a combination of Evolucumab and SOC vs. patients receiving SOC alone at 52-weeks.
The important datapoint from this study is whether patients were able to get to “healthy” LDL levels on combination therapy vs. SOC alone. As detailed in AMGN’s investor presentation below, at 52-weeks, 86% of patients got their LDL levels to <= 100 mg/dl compared with 16% of patients on SOC. 63% of patients get their LDL levels to <= 70 mg/dl compared with 2% on SOC alone.
It appears that AMG145 enhances the efficacy of statins, but does not affect LDL levels on its own. In one of the four studies comparing patients on AMGN145 with and without SOC, none of the patients reached target LDL levels.
Recently the FDA commented that companies working on a new class of cholesterol-lowering drugs known as PCSK9 inhibitors, may not have to prove they also reduce the risks or heart attacks and strokes. If this holds, AMGN and other companies with PCSK9 inhibitors could see a reduction in the cost and time to market for their new products. Recently however, two medical groups altered their guidelines suggesting doctors focus on drugs that have been proven to reduce risk for heart attack and stroke and not just help patients reach targets for lowering their LDL cholesterol.