Prolia like dosing for PCSK9s that will beat Repatha and Praluent in 5 years!

http://www.fiercebiotech.com/story/alnylam-medicines-co-say-next-gen-pcsk9-drug-has-blockbuster-potential/2015-08-29

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.

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.

"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%.

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.

 

RNAi's have bad safety profiles just like antisense. I bet that it doesn't make it to phase III.

 

This is 2nd geb rnai. Much better than first gen.

 

Sez yew.

 

Cumb in me bunghole! Spray day shizzz

 

I can't believe how low this board has gotten. You are Amgen employees? Really? You sound like 16 year old kids working the night shift at Taco Bell.

 

It's disgruntled Onyx employees.

 

There is a reason why we took their privileges away. What a bunch of cry babies.

 

More RIFs to Amgen!

• The Medicines Company (NASDAQ:MDCO) jumps 20% premarket on average volume in response to development partner Alnylam's (NASDAQ:ALNY)announcement that its investigational RNAi therapeutic, ALN-PCSsc, lowered LDL-C (bad cholesterol) up to 83% with a mean maximum reduction of up to 64% (+-5%) in an early stage study, results comparable to Amgen's (NASDAQ:AMGN)Repatha (evolocumab) and Sanofi (NYSE:SNY) and Regeneron's (NASDAQ:REGN) Praluent (alirocumab). The data were presented at the ESC Congress in London.
• What's notable in this case is the difference in dosing regimens. ALN-PCSsc was administered in one subcutaneous dose that was effective for over 140 days, giving it the potential for once per quarter or twice per year administration. Praluent is dosed once every two weeks and Repatha once every two weeks or once per month at a higher dose.
• ALN-PCSsc turns off PCSK9 synthesis in the liver. This is a different mechanism of action compared to Praluent and Repatha, both of which bind to PCSK9 in the blood.
• The Medicines Company will take the lead in developing ALN-PCSsc under the ORION Program. A Phase 2 study will commence by the end of the year and a Phase 3 trial is planned for 2017. The clinical development will include comparisons to the anti-PCSK9 monoclonal antibodies.
• The companies will host a conference call this morning at 9:30 am ET to discuss the results and their development plan.

 

http://www.bloomberg.com/news/articles/2015-08-30/alnylam-s-new-drug-may-prove-threat-to-sanofi-regeneron-amgen

“We’re seeing a durability that is really stunning,” Maraganore said by phone. “You go to four times a year, twice-a-year injections, it’s almost like having a flu shot for LDL at that point.”

Because it can be given so infrequently, ALN-PCSsc may address one of the biggest issues in medicine -- the fact that patients often stop taking their drugs, or don’t take them regularly. Among people prescribed statins, pills taken daily to fight bad cholesterol, about half stop taking them after a year, according to a 2013 study.

“We need to double down on compliance and get people to do things better, and one of the ways to do that is to lower the frequency of how often they have to do it,” Kim Williams, president of the American College of Cardiology, said in a phone interview.

“It’s a novel concept and it’s very encouraging” data, Williams said. “The big concern would be what happens over time and what happens in a larger number of patients. And when we have that, if they are parallel to the data they’ve gotten in a small cohort, it really sounds like a major advance.”

Patients taking the drug in a randomized trial saw bad cholesterol levels fall as much as 64 percent on average, compared with about a 20 percent decline for those taking a placebo. ALN-PCSsc showed no serious side effects in the study, which looked at 69 patients with high levels of bad cholesterol.

ALN-PCSsc has longer-lasting results because it uses a different tack to go after PCSK9. While other treatments tamp down the protein after it’s been made, ALN-PCSsc uses an approach, known as RNA interference or RNAi, that stops PCSK9 from being produced in the first place. By silencing select strands of RNA, which are the cell’s messengers that send instructions to manufacture proteins, RNAi works at “turning off the faucet” instead of treatments that “mop up the floor,” as Alnylam puts it.

 

Liver problems will undoubtedly show up in Phase II trials as the RNAi breakdown products build up in the tissue. Sure as the sun will rise tomorrow.

 

whatever fool! Three years out. Who cares?
Plenty of us know about this. You're just the fool who posted it.