How PCSK9 cholesterol drugs will shift pharma's pricing trends
The excitement surrounding PCSK9 inhibitors, the new class of anti-cholesterol drugs associated with 60% lower LDL-C levels and 50% fewer cardiovascular (CVD) events in early stage trials, is palpable. But now that issues of safety, clinical efficacy, and tolerability have begun being vetted in large, ongoing trials, the question many are asking is: "How much will these drugs cost?"
According to a recent Wall Street Journal article, Trogen Brennan, executive vice president and chief medical officer at pharmacy benefits giant CVS Caremark, anticipates that PCSK9 inhibitors will be "very expensive." In fact, Brennan and his colleagues have predicted annual costs between $7,000 to $12,000 on a per-patient basis, with overall costs in the $150 billion-per-year range.
The beginning of a pharmacoeconomic analysis
That contention has raised some eyebrows in the industry. And the actual pricing for the two PCSK9 inhibitors in development—evolocumab from Amgen and alirocumab from Sanofi/Regeneron—is still unknown.
At face value, $150 billion is a great deal of money. However, the combined costs of treating CVD in the U.S. exceeds $440 billion, according to the Centers for Disease Control and Prevention (CDC). Add to that the fact that one in three deaths in the U.S. is attributable to CVD, and it starts to become clear that spending more money on cholesterol-lowering drugs could not only save lives, but could potentially save money as well.
LDL-C reduction: More is better
Among the 83 million Americans who have some form of CVD, roughly 71 million have hypercholesterolemia, which increases their risk of CVD-related disability and death. And despite the availability of seven different types of statins, two-thirds of patients have high cholesterol levels that are not sufficiently controlled.
The link between LDL-C and cardiovascular risk is well established, as is the fact that reducing LDL-C improves CV outcomes. In a meta-analysis of 25 trials, including a total of 155,613 subjects, a 25 mg/dL reduction in LDL-C resulted in relative risk reductions as follows: 11.1% lower risk of vascular mortality; 14% lower risk of major vascular events; 16% lower risk of major coronary events; and 16% reduction in risk of mortality.
The results of this analysis, which were published in 2009 in Clinical Therapeutics, were based on statin-induced LDL-C reduction. To put that data into perspective, in Amgen's evolocumab safety study that followed 4,465 patients over a median period of 11.1 months, LDL-C levels decreased from a median of 120 mg/dL to 48 mg/dL—a 72 mg/dL reduction.
Price vs. adherence
While drug costs must be taken into consideration, the positive economic and health-related impact of this emerging therapeutic option should not be underestimated. Dr. Jay Edelberg, head of PCSK9 Development and Launch Unit at Sanofi, explains, "PSCK9 inhibitors are a paradigm shift for cardiology. LDL-C remains a risk factor for many patients, and the status quo is not good enough. We need to be able to provide the education about the efficacy, safety and tolerability of this treatment option."
Granted, there is a vast difference between the cost of generic ultra-high intensity stain therapy—$1,200 per year for atorvastatin 80 mg, according to Consumer Reports—and a price tag of $7,000 plus per year. Moreover, use of this level of therapy is associated with a potential LDL-C reduction of 46% to 54%. To put it lightly, that's significant.
However, according to Consumer Reports, higher doses of stains have been linked to muscle aches, soreness, tenderness, and weakness, with 5% to 10% of people experiencing these adverse events—a factor which most likely contributes to the low adherence rate of 54%. Even worse, high doses of statins have also been linked to rhabdomyolysis, a form of muscle breakdown that can lead to permanent kidney disease and even death.
Dr. Edelberg concedes that "statins have been a great treatment option for the last two decades," but the ability to effectively lower cholesterol in hard-to-treat patients—about 25% of the 83 million patients with hypercholesterolemia—could end up being a cost-effective proposition in the long term.