Alnylam, Medicines Co. say next-gen PCSK9 drug has blockbuster potential

Now that Amgen and the Regeneron/Sanofi team have scored pioneering approvals of two leading PCSK9 therapies, the race is already on to top the leaders with a new wave of even better drugs that can slash levels of bad cholesterol more efficiently. And Alnylam ($ALNY), alongside its partners at The Medicines Company ($MDCO), has staked out a claim to an RNAi treatment that could beat them all--some 5 years down the road.

Alnylam is reporting Phase I data at the European Society of Cardiology (ESC) Congress this morning for ALN-PCSsc that tackled a big slate of goals with a small set of patients. A total of 69 patients were divvied up into 11 cohorts, provided different dose ranges and divided the groups between single and multiple doses.

Alnylam CEO John Maraganore

All the data points aren't in yet, but the single 300-mg dose proved highly effective at knocking down PCSK9 and led to a mean average drop in LDL cholesterol of 44% at 140 days. Multiple doses scored higher, with "mean maximum" cuts--the top of the response curve as the treatment effect hit a high--of 64% ranging up to 83%. The single-dose averages are significant but lean toward the low end of the PCSK9 scale set by Praluent and Repatha, both newly approved by the FDA. Regulators noted that Praluent's slate of Phase III studies established a range of $36% to 59% cuts in cholesterol, with Repatha's approval coming in with a 60% average drop.

Shares of The Medicines Company shot up 16% on the news.

The Medicines Company, which in-licensed the program in a $205 million deal, will now take over development and follow a clearly defined Phase II through pivotal program--expected to start in late 2017--in an effort to prove that they can offer a treatment that can be given once a quarter, or perhaps even just twice a year, versus the pioneers' 26x yearly dosing schedule.

"We do think a once-quarterly dose of this drug is something that can be pretty transformative for patients," says Alnylam CEO John Maraganore. "People would like to have fewer injections," he notes, adding that the current crop of standard treatments in use score a nonadherence rate "well over 50%."

The Medicines Company is heading into a 5-year-long effort that will have much to prove as it expands from a handful of patients to the 5,000 ultimately needed to win over regulators on both sides of the Atlantic. As hepatitis C has proved recently, payers aren't averse to trading tougher dosing schedules for significant discounts. And long before The Medicines Company can step up, Pfizer ($PFE) and Experion both have rivals that are likely to beat this treatment to the market.

On the other hand, say the partnered developers, a 2x or 4x annual dosing schedule would also line up neatly with a patients' need for regular updates on exactly how well they're doing on lowering bad levels of LDL.

Medicines Co. CEO Clive Meanwell

"I can almost afford to have a healthcare professional by their side every time it (dosing) happens," says Medicines Company CEO Clive Meanwell.

"I think at the end of the day, the fact that we're 5 years behind is actually going to be very good for us," says Maraganore, a fierce champion of RNAi research and all things Alnylam. The leaders get to grow the market, and once it's mature, Alnylam, which stands to earn double digit royalties in its deal with Meanwell, and The Medicines Company can jump in with a drug that "could be very disruptive."

Alnylam grabbed a $25 million upfront for their deal on this drug, not the kind of down payment you would expect for a drug that Maraganore says clearly has blockbuster potential.

Says a vehement Maraganore: "If I knew then what we know now, there's no friggin' way we would have licensed this out."

But back in 2013, when they did the deal, they were working with preclinical data and the possibility they would need to use an IV formulation for a latecomer at the commercial end. It's up to The Medicines Company to complete the journey with much better prospects in mind.

- here's the release