Amgen's PCSK9 drug slashes 'bad' cholesterol in PhIII, stoking blockbuster hopes

Amgen ($AMGN) widened its lead among competing drugmakers in a promising new field of cardio treatments on the strength of late-stage results in which its in-development drug lowered LDL cholesterol by as much as 75%.

In results of 5 Phase III studies revealed at the weekend's American College of Cardiology scientific meeting, Amgen's evolocumab (AMG 145) cut "bad" cholesterol by between 53% and 75% in trials involving more than 4,000 patients. The drug, which blocks the protein PCSK9 to help the body clear LDL cholesterol from the blood, is part of a new class of statin-beating injectables that promise to bring in more than $10 billion at their peak, and Amgen is expected to file for FDA approval this year, giving it a lead on similar offerings from rival tandem Sanofi ($SNY) and Regeneron ($REGN) and third-place Pfizer ($PFE).

Amgen's fleet of promising data includes a 52-week study in which evolocumab reduced mean LDL cholesterol by 57% compared to placebo; two trials finding the drug safer and more effective than Merck's ($MRK) Zetia; and one in which a combination of evolocumab and statins charted a 75% cut in the harmful lipoprotein. The biotech giant had released top-line results from each trial but saved the specifics for the crowd at ACC 2014 in Washington, DC.

Beyond the strong efficacy results, not one of Amgen's trials found significant evidence of neurocognitive side effects with evolocumab, the company said, news that may quiet down some concerns about the safety of PCSK9 blockers. Earlier this month, Sanofi revealed that the FDA is looking into the potential for cognitive impairment with the new class of drugs, asking the drugmaker and its partner to keep tabs on the issue through their 12-study Phase III program. Amgen later said it got the same notice from regulators, leading spooked investors to dump shares in all three companies and worry that the FDA might hold out for long-term outcomes data before approving any PCSK9 drugs.

Those worries seem to have subsided by and large, but Amgen still has 8 more trials to report out in its expansive Phase III program for evolocumab, including one that will track patients for years to cull data on whether the drug can reduce the number of cardiovascular events in the long term. Pfizer, Sanofi and Regeneron are also plotting such longitudinal studies, and their results will likely dictate whether PCSK9 inhibitors reach their full sales potential. The FDA has said it will consider reductions in LDL cholesterol as surrogate endpoints for cardiovascular improvement, but payers may hold out for long-term outcomes data before accepting the new drugs, which could cost thousands of dollars per year.

Evolocumab remains the top prospect for Amgen and its multibillion-dollar R&D operation, and the company could find its way onto the market between 6 months and a year before its closest competitor in the PCSK9 space, giving Amgen a chance to reap as much as $3 billion a year, analysts figure.

- get more on the first three studies
- read Amgen's releases on the fourth and fifth (PDFs)