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Large reductions in the price of PCSK9 inhibitors are still needed for them to provide decent value for money, researchers found, as relatively small rebates from manufacturers aren't enough to make these drugs accessible.

Using current annual wholesale prices of ezetimibe (Zetia; $3,818) and PCSK9 inhibitors ($14,542), Kirsten Bibbins-Domingo, PhD, MD, of San Francisco General Hospital, and colleagues performed a cost-effectiveness analysis based on FOURIER trial outcomes data.

PCSK9 inhibitors on top of statins prevented an estimated 2.9 million major adverse cardiovascular events compared with adding ezetimibe, yielding an incremental cost-effectiveness ratio (ICER) of $450,000 per quality-adjusted life year (QALY) with these drugs. This means the price-tag of PCSK9 inhibitors needs to be in order for them to meet a willingness-to-pay threshold of $100,000 per QALY, they reported online in JAMA.

If one assumes the drugs have no direct effect on cardiovascular death as shown in FOURIER, the ICER jumps to $1.8 million/QALY.

"PCSK9 inhibitor use in patients with atherosclerotic cardiovascular disease was not cost-effective at 2017 prices, and these updated analyses based on FOURIER estimates suggest that even greater price reductions than previously reported are required to meet cost-effectiveness thresholds."

Bibbins-Domingo's group previously showed that the 2015 price of PCSK9 inhibitors would need to be reduced by 69% (to $4,536 per year) to be cost-effective.

Manufacturers typically offer 25%-30% discounts -- clearly, this isn't enough, the authors said.

Furthermore, Amgen's rebate model for evolocumab (Repatha) has refunds for drug costs issued if patients experience major adverse events while receiving PCSK9 inhibitor therapy. Bibbins-Domingo's group said this was "unlikely to meaningfully reduce drug expenditures given the low overall major adverse cardiovascular event rate (approximately 3% per year)."

"The results of this new cost-effectiveness analysis are not encouraging," said Daniel B. Mark, MD, MPH, and Kevin A. Schulman, MD, MBA, both of Duke Clinical Research Institute in Durham, N.C., given that "the pool of candidates for PCSK9 inhibitor drugs is enormous."

In an accompanying editorial, they posed the question: "What should be done about a therapeutic innovation that provides incremental clinical benefits relevant to a large group of patients, appears, so far, to have acceptable safety, and yet is neither cost-effective nor affordable?"

"Neither physicians nor patients have sufficient policy influence to alter the way these access or investment decisions are made. Congress has the power to make changes but not the will. Payers are thus put in the unenviable position of being forced to make life-altering decisions for their health plan members on financial grounds," Mark and Schulman said.

If drugs keep getting priced out of reach, they suggested that players in the healthcare industry will stop caring and stop trying to fix the problem.

"Painful as it is, draconian restrictions on access to drugs that are priced for profit maximization out of proportion to any value proposition and budget tolerances may continue to be the only way medicine can send a strong signal to innovators that their future rewards are tied not just to scientific advancement but also to affordability."

The present analysis by Bibbins-Domingo's group relied on the Cardiovascular Disease Policy Model to simulate the cost-effectiveness of PCSK9 inhibitors.

After applying the FOURIER inclusion criteria, the model included 8.9 million U.S. adults with atherosclerotic disease who needed additional lipid lowering on top of ongoing statin therapy (mean age 66; 61% men). The study population started off with a mean LDL cholesterol of 104 mg/dL.

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