Can Sanofi/Regeneron's new data one-up Amgen in megablockbuster PCSK9 field?

When is cholesterol fighting a game of six of one, half dozen of the other? Could be when the contest is between Amgen and its PCSK9 inhibitor evolocumab, and Sanofi and Regeneron's rival alirocumab. Despite some dramatic new data from the latter team--and a first-up filing with the FDA by Amgen--analysts figure on a dead heat once the drugs hit the market.

In fact, based on the results of a physician survey and their own number-crunching, Leerink Partners analysts figure that evolocumab and alirocumab will split the PCSK9 market between them. Both will achieve peak sales of $4.3 billion, base case, and up to $6.8 billion each if all goes well, the analysts predict. If and when Pfizer and Eli Lilly bring their PCSK9 rivals to market, what happens? Not a lot. The analysts see each of the first two entrants hanging onto a 40% share.

The Leerink report follows a couple of big events. First, Amgen ($AMGN) filed evolocumab for FDA approval, putting it first up for agency review. And second, Sanofi ($SNY) and Regeneron ($REGN) unveiled four new sets of data at the European Society of Cardiology meeting, showing that when it comes to cutting LDL levels in statin-intolerant or otherwise hard-to-treat patients, alirocumab rocks.

But even more impressive was this: Safety data from one of the studies--Odyssey Long Term, with 2,341 participants--showed that patients treated with alirocumab were about half as likely to experience a heart attack, stroke, hospitalization or death as were patients on placebo.

These are somewhat speculative results--a post-hoc analysis, on a study not powered for outcomes--so the real results story won't be proven till the long-term Odyssey Outcomes trial reads out. But the implications are huge. After all, the holy grail of cardiovascular drug development is demonstrating hard evidence of improved patient outcomes.

Thing is, those figures could well demonstrate the case for PCSK9 drugs, period. Strong outcomes would be expected from a drug--or drugs--that can cut LDL cholesterol so dramatically, the Odyssey Long Term study's lead author said Tuesday during a call with investors. Given that Amgen's PCSK9 inhibitor also has a dramatic effect on LDL levels, then the payoff would theoretically be similar.

Dr. Jennifer Robinson

And even that lead investigator--Dr. Jennifer Robinson of the University of Iowa--could find little to distinguish Sanofi and Regeneron's entrant with Amgen's, efficacy-wise. As far as effects on LDL cholesterol go, the trial results for both are about the same, or 55% at 12 weeks, she said Tuesday during the investor call.

Amgen did beat Sanofi and Regeneron to filing for FDA approval, obviously. But the alirocumab team leveled that playing field, too--by buying a priority review voucher that could speed up agency review once its application is accepted.

What alirocumab has that Amgen's drug doesn't is more flexibility in dosing, Robinson said Tuesday. "Physicians can individualize therapy," she said, something that's not as easily done with evolocumab.

But can that translate into a differentiation that patients, physicians--and payers-- might pay attention to? First, Sanofi and Regeneron will have to get doctors familiar with their med, which trails Amgen's in awareness among physicians, according to Leerink's survey.

Doctors did say that decent outcomes data could really spur their use of PCSK9 drugs--by up to 43%. And as Robinson noted during that investor call, the Odyssey Outcomes study could build a case for that.

The trial looks at alirocumab in patients with acute coronary syndrome, as an add-on to statin therapy. If the Sanofi/Regeneron med delivers strong outcomes results in this trial, then that would make a case for routinely treating ACS patients with alirocumab on top of a statin. And that would take alirocumab--and perhaps the PCSK9 class--beyond the pool of patients who can't tolerate statins or don't get results from them. It would make the potential population much, much larger.

- read Regeneron's statement