Dive Brief:

• A new estimate from a closely watched research group argues the price of Amgen Inc.'s cholesterol drug Repatha should be between 85% and 88% less to be considered cost-effective, setting a new lower bound in the back-and-forth debate over the value of PCSK9 inhibitors.
• In an updated analysis of a previously published report, the Institute for Clinical and Economic Review revised down its value-based price benchmark for Repatha to between $1,725 and $2,242 a year — a steep discount to the drug's current annual list price of near $14,500.
• Amgen has pushed back forcefully against ICER's calculations, which the drugmaker says don't "accurately assess the real world value of reducing the risk of heart attacks and strokes." A study sponsored by the company and published in August found Repatha would be cost effective at a list price of $9,669.

Dive Insight:

Key to ICER's new bargain-basement estimate of Repatha's (evolocumab) cost-effective list price were findings from Amgen's FOURIER cardiovascular outcomes trial. While the landmark study proved Repatha's heart benefits, results showed the drug had no statistically significant effect on cardiovascular death.

ICER's original analysis of Repatha in 2015 had assumed such a broad effect. Adopting a more conservative approach following FOURIER significantly lowered the value-based price benchmark for the drug.

Under the updated model, adding Repatha to statin treatment would result in an incremental cost-effectiveness ratio of $1.3 million per quality-adjusted life year gained compared to statins alone. That's more than triple the $300,000 per QALY that ICER had calculated previously, and both are well above the $100,000 to $150,000 per QALY threshold ICER prefers.

Notably, ICER's update only applies to use of Repatha in patients with athersclerosis cardiovascular disease with LDL-C levels still above target. It specifically doesn't cover other patient populations such as familial hypercholesterolemia, which may have different value propositions.

Also at issue is whether FOURIER's follow-up period undersells Repatha's effect on cardiovascular mortality. The treatment's benefit grew over time, perhaps suggestive of a greater effect further out from beginning treatment.

Amgen holds that ICER's methodological assumptions are faulty and has undermined the group's conclusions, standing by Repatha's benefit.

"It is standard practice to extrapolate CV mortality benefit when modeling long term benefit. In fact, 99% of CV models assume a mortality benefit even though 88% of those studies had no clinical trial data to support the benefit," Amgen said in a statement.

Yet, cost has been a major barrier to securing more favorable coverage from payers. Both Repatha and its rival PCSK9 inhibitor Praluent (alirocumab) have struggled to gain traction commercially and initial approval rates by insurers of new prescriptions have remained low.

ICER's reports may be strengthening payers' hands, too.

"We plan to use this report in our ongoing negotiations with manufacturers, as this update will help inform our efforts to secure a price that represents a fair deal for Veterans and the US taxpayer," said Chester Good, chair of the medical advisory panel for pharma benefits at the Department of Veteran's Affairs, in a statement provided by ICER.

In June, ICER said it would help the VA integrate its drug assessment reports into the agency's formulary management process, an agreement that gives ICER's conclusions more weight.