Amgen gains 1st US CV drug OK with Corlanor

Amgen gained its first US cardiovascular drug approval on 15 April with the FDA giving its nod to the firm's heart failure medicine Corlanor (ivabradine).

The drug already is sold in over 100 countries for chronic stable angina and in 88 nations as a treatment for heart failure, Dr Rob Scott, vice president of global development at Amgen, told Scrip.

It is the first new heart failure medicine OK'd in the US in nearly a decade, Dr Scott said.

Amgen spokeswoman Kristen Davis said the company has set Corlanor's monthly wholesale acquisition cost at $375, or $4,500 per year.

Specifically, Corlanor is indicated in the US to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction at or below 35%, who are in sinus rhythm with resting heart rate at 70 beats or above per minute and either are on maximally tolerated doses of beta blockers or have a contraindication to beta blocker use.

Heart failure affects about 5.7 million people in the US – a figure expected to grow by 46% by 2030, Amgen said.

Heart failure costs an estimated $31bn in the US each year, with the majority of the cost related to hospitalizations. Those costs are expected to increase almost 127% to $70bn by 2030.

Corlanor works by inhibiting the so-called "funny" current in the sinoatrial node – the body's cardiac pacemaker.

"It slows the rate of polarization in the cells in the sinoatrial node and modulates heart rate," Dr Scott explained. "It slows the heart rate but it has no impact on force of contraction of the ventricles or conduction."

"As we've learned for many years, heart rate is very closely related to outcomes in heart failure, so patients with mild heart rates in heart failure have worse outcomes than patients with lower heart rates," he said. "By slowing the heart rate, we can expect to improve outcomes."

Corlanor's new drug application was based on a large, multicenter, randomized, double-blind, placebo-controlled Phase III outcomes trial, known as SHIFT, which compared the drug to placebo on top of standard-of-care therapies, including beta-blockers, in more than 6,500 patients in sinus rhythm with reduced left ventricular function and heart rate at or above 70 beats per minute.

The results of the study showed that Corlanor significantly reduced the risk of the primary composite endpoint of hospitalization or cardiovascular death for worsening heart failure, with 18% relative risk reduction (RRR), versus placebo.

But the treatment effect reflected only a reduction in the risk of hospitalization for worsening heart failure.

There was no favorable effect on the mortality component of the primary endpoint.

There was a 26% RRR in the risk of hospitalizations for worsening heart failure.

The FDA previously granted fast-track status and priority review to Corlanor, although the drug's approval initially was delayed, after which Amgen had not expected to hear from the FDA until 28 May.

But the agency ended up granting the approval early.

Corlanor will be dispensed with a patient medication guide, which provides instructions for its use and important drug safety information, regulators said.

The FDA advised healthcare professionals to counsel patients about the risk of harm to an unborn baby. Women also should not become pregnant while taking Corlanor.

Amgen gained the rights to Corlanor under a July 2013 deal with French drug maker Servier

Amgen has also received an exclusive option to develop and commercialize Servier's investigational molecule, S38844, for cardiovascular diseases in the US.

Through the collaboration, Servier obtained rights to commercialize Amgen's omecamtiv mecarbil, a small molecule activator of cardiac myosin, in Europe.

Amgen is developing omecamtiv mecarbil under a collaboration with Cytokinetics in the US.

The drug is in Phase II development, Dr Scott said.

PCSK9 excitement

Perhaps the drug in Amgen's CV pipeline that's been getting the most attention lately is its proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab, whose biologics license application (BLA) currently is under review at the FDA as a cholesterol-lowering medicine.

This past November, the company became the first firm in the US to submit an application to the FDA for a PCSK9 inhibitor.

Regulators set 27 August as the Prescription Drug User Fee Act (PDUFA) action date.

But Regeneron and Sanofi may be the ultimate winners to the US market with a PCSK9 inhibitor in the CV space after gaining a US priority review in January for their BLA for Praluent (alirocumab) and a PDUFA date of 24 July – a full month ahead of Amgen's evolocumab, although the FDA could certainly make an earlier-than-expected decision on either drug or delay one or both.

Payers, however, have made PCSK9s their new target for trying to force lower prices before the medicines even hit the US market.

Indeed, in February, four executives at CVS warned the costs to the US healthcare system of using PCSK9s to treat high cholesterol could reach $200bn annually.

Even if the medicines were limited in the US to just the familial hypercholesterolemia and severe hypercholesteremia populations – or about 1.6 million people – at a cost of $10,000 per patient, that's $16bn annually, they wrote in a 17 February article published in the public policy journal Health Affairs.

First, they said, there will be shock over the money spent on PCSK9 inhibitors. But then there will be a demand for action.

"Perhaps the costs of PCSK9 inhibitors will push us to develop some consensus about the pricing of new specialty medications, as part of a more thoughtful discussion about the use of scarce resources on behalf of patients," they said.