ACC – Praluent’s Odyssey ends with a whimper

It was telling that Regeneron and Sanofi were in just as much of a rush to tell the world that they were cutting prices on cholesterol-lowering drug Praluent than they were to discuss the results of its long-term outcomes trial released Saturday at the American College of Cardiology.

The 15% reduction in major cardiovascular events recorded by Odyssey Outcomes was no better than that seen with Praluent’s PCSK9 rival, Amgen’s Repatha, and underscores that this class is a potent but expensive way to reduce low-density lipoprotein (LDL) cholesterol. Now the path forward is in negotiating Praluent’s price down to a level where payers see it delivering value, and in focusing on the sicker population that sees a mortality benefit.

Underwhelming value

It is clear that Regeneron and Sanofi are aware that the benefits of Praluent are underwhelming from an economic standpoint at the list price of $14,000 a year. The companies made much of a new programme to reduce the cost of the drug to “US payers that agree to reduce burdensome access barriers for high-risk patients”. It should be pointed out that the burdensome access barriers are there because Praluent costs so much.

Released simultaneously, a new analysis by the cost-effectiveness body the Institute for Clinical and Economic Research (ICER) on Praluent, completed in collaboration with Regeneron and Sanofi, judged the drug to be cost-effective for the patient population enroled in Odyssey Outcomes at a price between $2,306 and $3,441 a year.

All of this could serve to mitigate investor disappointment when trading opens on Monday, possibly saving both partners from the 7% hit Amgen received when the results of the Fourier trial were toplined at the American College of Cardiology meeting a year ago (ACC – No Repatha of glory, March 17, 2017).

Doctors: we want Praluent

As with Repatha’s Fourier study, Odyssey Outcomes must be judged a clinical success, and cardiologists were keen to say they would want to use Praluent with statins in more heart disease patients. While Fourier enrolled high-risk patients with elevated LDL, Odyssey Outcomes enrolled patients with acute coronary syndrome. Selecting a sicker patient population along with longer follow-up meant some observers believed that Odyssey Outcomes would yield a more impressive result.

The 15% reduction in myocardial infarctions, strokes, unstable angina and cardiovascular death – the primary endpoint – achieved statistical significance, although it just met the minimum assumptions of the trial’s designers. The absolute risk reduction was 1.6%, and the trial’s lead investigator, Gabriel Steg of Université Paris-Diderot, estimated that 64 people would need to be treated to avert one cardiovascular event.

Tantalisingly, Odyssey Outcomes detected a numerical all-cause mortality benefit, but because of multiplicity the nominal p value of 0.026 was statistically non-significant.

In patients with baseline LDL of greater than 100mg/dl, the benefit was stronger – a 24% reduction in cardiovascular events and an absolute risk reduction of 1.7%. Dr Steg estimated that 29 patients would need to be treated to prevent one cardiovascular event in this patient group. And just as importantly, a significant improvement in mortality was detected in this population, with a 29% reduction in death from any cause.

These patients are emerging as an economically important target population – ICER put a value-based benchmark price of $4,460 to $6,578 here.

“As a clinician given the cost conscious environment we’re in we have to ask, ‘With whom do we start?’“ Dr Steg said. “As a clinician I have to start somewhere, and the best group is the post-ACS patients with the highest level of LDL.”

Minimum

Commercially, it was crucial that Praluent show at least a minimum cardiovascular benefit. Amgen has won the right to market Repatha on the basis of the Fourier trial results – its label now states it is indicated to reduce the risk of MI, stroke, and coronary revascularization in adults with established cardiovascular disease – and Odyssey Outcomes should permit Regeneron and Sanofi to do the same.

Praluent was launched first, but Repatha has been pulling away – EvaluatePharma’s sellside consensus forecasts sales of $2.5bn for the Amgen agent, to $1.3bn for Sanofi and Regeneron. A clear benefit in cardiovascular outcomes, an identifiable patient subgroup in which it is most effective, and a pricing programme designed to lure payers could help Praluent claw back share and even, perhaps, grow the market for these agents.

However, it does not appear likely that either drug will ever live up to their pre-launch hype, which suggested combined 2022 sales of more than $9bn. PCSK9s may live in biopharma history as the great drugs that flopped commercially because the price that the market was willing to bear was grossly misjudged.

To contact the writer of this story email Jonathan Gardner in Orlando at [email protected]or follow @ByJonGardner on Twitter