Lackluster Amgen, Sanofi PCSK9 drugs could be under major threat from a new rival: analyst

If approved, The Medicines Company's inclisiran could be a bigger threat to Amgen's Repatha than to Praluent because of Repatha's better potential, SVB Leerink analyst Geoffrey Porges says. (Amgen)

It’s no secret that the two existing PCSK9 cardiovascular drugs on the market, Amgen’s Repatha and Regeneron and Sanofi’s Praluent, are suffering from painfully slow launches. And on top of that, they could soon face a serious threat thanks to a positive phase 3 readout from a more convenient option, one analyst argues.

The Medicines Company on Monday said its investigational cholesterol-lowering therapy, inclisiran, had hit the primary endpoint of a phase 3 trial. As Repatha and Praluent do, the drug aims to reduce PCSK9 production to help remove bad cholesterol from the bloodstream. But unlike an antibody-drug—as is the case with Repatha and Praluent—inclisiran uses small-interfering RNA to target PCSK9.

Inclisiran also boasts a key advantage that could make it the preferred drug by physicians and patients: convenience. While Repatha and Praluent are given every two weeks or once monthly, inclisiran is administered as an under-the-skin injection every six months after an initial two doses given three months apart, according to The Medicines Company's phase 3 Orion-11 trial design.

Although the New Jersey company didn’t unveil detailed data, how it worded the press release seems to suggest the efficacy and safety results were positive and consistent with previous studies, SVB Leerink analyst Geoffrey Porges wrote in a Tuesday note to clients. “If this is indeed true, it makes the already challenging market for the antibodies unattractive,” he said.

By comparing results from previous inclisiran phase 2 studies with Praluent’s and Repatha’s trials that had similar trial design and inclusion criteria, Porges found “inclisiran has showed similar efficacy” to those marketed drugs in terms of LDL-C lowering.

RELATED: Medicines Company's PCSK9 drug hits phase 3 efficacy goals

Specifically, in the Orion-1 trial, inclisiran showed it could lower bad cholesterol by 51% at month six in patients already on statins, and then sustained the 50%-plus level over three years in the Orion-3 extension study. The rates for Praluent in its Odyssey trial and for Repatha in the Fourier trial were 58% at week 24 and 57% at week 72, respectively.

“Unless there is some surprising relatively rare severe adverse event in the data,” inclisiran also appears to have no concerning safety issues, with no treatment-related elevations of liver enzymes or changes in renal function, Porges figured.

Amgen and the Regeron-Sanofi pair are already fighting bitterly in the PCSK9 realm, marked by recent back-on-back list price cuts of the same 60% and ongoing patent brawls across the globe. But of the two already-approved therapies, Amgen’s Repatha would take a more serious blow on competition from inclisiran, in Porges’ view. But it’s simply because Repatha already has a better outlook.

RELATED: Sanofi, Regeneron score a Praluent boost—and Repatha equalizer—with new CV nod

Currently, consensus on the Street has Repatha sales peaking at about $2.4 billion and Praluent’s reaching only around $1 billion, Porges noted.

In the second quarter, Repatha racked up sales of $152 million, only 3% above its haul over the same period last year. The number would have been better if it weren’t for the heavy discount, Amgen’s EVP of global commercial operations, Murdo Gordo, said during a conference call in July. In fact, U.S. unit growth was 66%, he said. Meanwhile, Sanofi only recorded Praluent sales of €66 million ($73 million).

Because of Praluent’s already meager potential, Regeneron and Sanofi would possibly “question their own participation and scale back their commercial and clinical investment,” Porges argued. If the companies simply stop counting on the drug, he said, it “would be a net positive contribution to profitability, cash flow and value.”

However, Amgen considers Repatha a major contributor to its future growth. Therefore, while it’s more likely to hang with inclisiran, its higher exposure to the market could mean more meaningful losses at the entry of The Medicines Company’s drug, Porges said.

We should know more soon. The Medicines Company will present detailed data next week at the European Society of Cardiology Congress. Its U.S. FDA filing is expected by year's end.