PCSK9 adcomm preview: what's at stake

An FDA advisory committee will discuss whether to approve the next generation of cholesterol-lowering treatments this week.
An FDA advisory committee will discuss whether to approve the next generation of cholesterol-lowering treatments this week.

An FDA advisory committee will weigh whether two experimental cholesterol-lowering drugs—part of a highly anticipated new class of drugs known as PCSK9 inhibitors—are fit for approval Tuesday and Wednesday.

The FDA is not required to follow the panel's recommendation but it usually does.

The central question for the committee will be whether the cholesterol-lowering benefits of Sanofi/Regeneron's Praluent (alirocumab) and Amgen's Repatha (evolocumab) merit supporting the drug's approval. Sanofi and Regeneron developed the alirocumab antibody under a collaborative research agreement that began in 2007.

If approved, cardiologists would have an additional tool in their arsenal when treating patients with high cholesterol, allowing patients the option of an injectable drug they can take at home. A survey of 50 cardiologists conducted by Jefferies in March found that doctors expect to prescribe PCSK9 inhibitors to up to 23% of their high-risk patients before the outcomes data is released and that the percentage of prescriptions could rise to between 29% and 37% of patients if the drugs produce a mortality benefit.

The firm estimates the drugs could reach $5 billion in sales in their first year on the market with the potential to reach $12 billion by 2019 if outcomes data is positive.

Dr. James Smith, deputy director of the FDA's division of metabolism and endocrinology, told members of the committee that the central issue regarding this drugs' application was whether these drugs' ability to lower cholesterol outweighs their risks. “For what population(s), if any, does the LDL-C lowering benefit of evolocumab exceeds its risks to support approval?” he said.

Throughout the development process for these drugs, the FDA's stance has been that it would consider approval based on how effective they are in reducing cholesterol levels rather than on their ability to reduce the chance of a major cardiovascular incident, like a heart attack or a stroke.

In the same memo, Smith asked the committee members to “carefully consider whether [the benefit exceeds the risk] in the absence of a regulatory requirement to demonstrate benefit in a CV outcomes trial,” further reinforcing the agency's stance.

Sanofi/Regeneron and Amgen are both currently conducting outcomes trials for these drugs with the hope of promoting additional claims for these products. The results of these studies are expected to be available no later than 2017.

Committee members will also be tasked with identifying the proper patient population for these drugs. At this stage, it appears these drugs will likely serve two patient populations: the statin intolerant and those with a rare condition called homozygous hypercholesterolemia, which affects roughly 620,000 Americans.

While many doctors use statins to lower cholesterol in patients, some patients don't tolerate the drugs well or are unable to get their cholesterol levels under control despite using the maximum allowed dosage of statins like Lipitor.

Homozygous hypercholesterolemia is an inherited disorder that causes high levels of cholesterol at birth and can lead to heart attacks at an early age. The condition is currently treated with Aegerion's Juxtapid and Genzyme's Kynamro.