Sanofi, Regeneron point to potential heart benefit in PCSK9 data dump

The development team from Sanofi ($SNY) and Regeneron ($REGN) journeyed to the ESC Congress in Barcelona this weekend to detail the impact their late-stage PCSK9 drug alirocumab has on bad cholesterol, drawing some high-profile attention for a batch of preliminary numbers suggesting a trend toward lower cardiovascular risks.

Engaged in a high-stakes race to the regulators with a rival program at Amgen ($AMGN), the Sanofi/Regeneron camp detailed numbers from four big studies among thousands of patients suffering from hypercholesterolemia. In the biggest study, the ongoing Odyssey Long Term trial, there was a 61% plunge in LDL compared to a 1% increase in the placebo arm. And four out of 5 patients achieved their targeted reduction in LDL--usually on the starting dose.

"As physicians, we often start patients on a lower dose of a medication and only increase it if needed. In these trials, the majority of patients who were started at a 75 mg dose of alirocumab, were able to achieve their target LDL-C goals while remaining on their initial dose," said Harvard's Christopher Cannon in a statement.

The key distinguishing factor for alirocumab, which has to be studied for a longer period before investigators can make a final assessment, will be a reduction in the risk of cardiovascular events like death, stroke and angina. And there investigators say that they have so far tracked a 1.4% rate of events in the PCSK9 arm compared to a rate that's more than twice that level--3%--in the placebo arm. That long-term health benefit is crucial to the ultimate success of this drug, which is aimed at a potential blockbuster niche that has attracted a swarm of contenders.

That's a point that's crystal clear to Amgen as well. On Sunday, a spokesperson for the company flagged a lower rate of cardio events after 52 weeks of therapy in one of its evolocumab studies--though like the Sanofi/Regeneron team, investigators have yet to nail down the kind of hard endpoint on a health benefit that would satisfy the FDA. And there are still safety concerns to consider.

Earlier this year, a fretful FDA notified Sanofi and Regeneron that there were some serious concerns about the neurocognitive effect of these drugs, a factor for the entire class of cholesterol treatments. That helped spark fears that the agency could wind up demanding long-term results from studies like Odyssey, which could delay the entry of these drugs. But the market seems to have gotten over the jitters as they look for a near-term approval.

Some analysts, though, were quick to pick up on the numbers for neurocognitive disorders in this latest study. The drug arm recorded a 1.2% rate of adverse events, compared to only 0.5% in the placebo arm, according to a slide that was prominently displayed on Twitter this morning. In the past, though, these neurocognitive disorders typically never went much past fuzzy thinking, and it was easily reversed by stopping the cholesterol medication.

Alirocumab represents one of Sanofi's best near-term hopes for a major league drug approval after recording a number of clinical setbacks in recent years, while Regeneron is taking charge in the clinic as it pushes to expand on its successful drug franchise. Together they bought a priority review voucher from BioMarin ($BMRN) for $67 million, cutting 4 months out of the regulatory process in hopes of beating Amgen, which is pushing a rival program for evolocumab. Amgen filed three days ago at the FDA, while Sanofi/Regeneron say they'll follow up before the end of the year.

Potential peak sales figures have been bandied around for some time now, but a number of analysts believe this drug class has the potential to earn a multibillion-dollar return. And the high stakes have attracted several high-level players in the pharma world.

In addition to Amgen and the Sanofi/Regeneron team, Pfizer is closing in with its own late-stage program for bococizumab; Roche's ($RHHBY) big Genentech operation has RG7652 in late-stage development, though it rarely talks about it; and Eli Lilly ($LLY), which can be notoriously slow in the clinic, just finished a Phase II study for LY3015014 in June, according to clinicaltrials.gov.

Amgen has laid out data from 10 studies for their candidate, finding a reduction in LDL ranging from the mid-50s to the mid-70s, depending on dosing. You can expect to hear plenty about various comparison data in coming months. 

- here's the release

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