The Q&A: Contextualising Repatha’s FOURIER performance – the four key questions

What did FOURIER show?

Investors were none too thrilled by what they saw in detailed results from the FOURIER outcomes trial of Repatha (evolocumab), causing a steep selloff in the company’s shares that wiped 6 percent – or almost $8 billion – off of its market share on March 17.

Specifically, Repatha was shown to reduce the risk of cardiovascular death, heart attack, stroke, hospitalisation for unstable angina, or coronary revascularization event – the study’s primary endpoint – by 15 percent in patients already receiving maximally tolerated statins. According to ISI Evercore analyst Umer Raffat, despite achieving statistical significance on this measure the results did not live up to the 20-percent risk reduction for which the Street had been hoping.

What’s more, the anti-PCSK9 mAb fell short of demonstrating statistical significance in lowering the risk of cardiovascular or all-cause deaths, and in fact the hazard ratios actually showed a small trend in favour of placebo.

The readout was far from a worst-case scenario for Amgen though, as Repatha’s safety profile looked remarkably clean and the drug did manage to live up to expectations on a key secondary endpoint by reducing the risk of major cardiovascular event (MACE) by 20 percent.

What impact will this have on use of Repatha?

The consensus among analysts, which was supported by a KOL who spoke with FirstWord over the weekend, is that the FOURIER results will serve to modestly boost the use of and reimbursement for Repatha. However, the magnitude of risk reduction achieved was not sufficient to bring about a meaningful change in either physicians’ practice patterns or payers’ coverage decisions.

Also see: KOL Views: FOURIER not a big win for Amgen’s Repatha but far from an unmitigated disaster, according to leading cardiologist

That said, there are signs that the FOURIER data could provide a boost. CVS Caremark released a statement noting that the pharmacy benefit manager expects that they will result in an increase in the number of patients using Repatha and PCSK9 inhibitors, though it will depend to a certain extent on guidelines that cardiology groups will be updating in the coming weeks.

What does it mean for Praluent?

What exactly the future holds for Praluent (alirocumab), a competing anti-PCSK9 mAb from Regeneron and Sanofi, is unclear at this point. Amgen is seeking a permanent injunction against the product that could potentially lead to its removal from the market.

In the meantime, the FOURIER results could represent a bit of a headwind for Regeneron and Sanofi in the sense that – all things being equal – physicians may tend to prescribe a drug in Repatha with positive (however modest) outcomes data rather than one without them, especially in light of the stoppage of Pfizer’s bococizumab, which reinforces the possibility that all anti-mAbs may not be born equal.

Regeneron shares ticked down 3 percent on March 17, while Sanofi finished off 1 percent on the day.

What other programmes were affected?

The FOURIER results had a noticeable impact on a number of companies developing dyslipidaemia programmes, as they call into question the amount of cardiovascular risk that can be eliminated by additional lowering of cholesterol, and by extension their commercial potential.

Shares of The Medicines Co. opened the day off almost 25 percent as investors’ enthusiasm for inclisiran, an antisense oligonucleotide against PCSK9 that looked capable of twice-yearly dosing in Phase II testing, took a hit. The company managed to clawed much of the lost value back and closed down only 8 percent.

Esperion Therapeutics also took the news hard, shedding 20 percent of its market cap as the Street became increasingly cautious about the prospects for its bempedoic acid, a small molecule ATP citrate lyase inhibitor that decreases LDL cholesterol via a similar mechanism to statins and anti-PCSK9 mAbs. The product is in Phase III testing.

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