A novel drug still in phase 1 studies could dramatically lower cholesterol with only a few injections each year. Because the drug could be given during regular visits to the doctor it might help solve the thorny problem of drug compliance and adherence. Like the recently approved monoclonal antibodies alirocumab and evolocumab, the drug targets PCSK9 to lower LDL, but the new injectable drug, known for now as ALN-PCSsc, uses RNA interference technology to inhibit the synthesis of PCSK9 in the liver. The drug was created by Alnylam Pharmaceuticals and is now being developed by the Medicines Company.
Initial results from a phase 1 study were presented on Sunday at the European Society of Cardiology meeting in London.
I almost never write about drugs this early in development, and it should be noted that there are other promising cholesterol lowering drugs further along in development, including oral drugs from Pfizer and Esperion that have attracted a lot of attention. What’s most intriguing about this new drug is the potential that it might help solve the compliance problem. “You can change adherence,” said Clive Meanwell, head of the Medicines Company, in an interview at the ESC. For now though it is important to emphasize that the drug is still in phase 1, and, as we all should know by now, almost anything can happen as a drug moves forward into more rigorous testing.
Clive Meanwell, Chairman and CEO of the Medicines Company, and Kevin Fitzgerald, Alynlam Pharmaceuticals
In the phase one trial the drug reduced LDL by a mean of 64%, which is comparable to the effect of the PCSK9 inhibitors. The poster at the ESC was presented by Kevin Fitzgerald, a scientist at Alnylam. LDL remained lowered for more than 140 days, thereby supporting a strategy of quarterly, and possibly even bi-annual, treatments.
The drug was well tolerated with no clinically significant adverse events occurring in the ongoing phase 1 trial. 76 patients with elevated cholesterol levels were studied. The trial is now fully enrolled and continues to follow patients and collect data. Further results from the study will be presented at the American Heart Association meeting in November.
The drug was initially developed by Alnylam Pharmaceuticals. Before it appreciated the full potential of the compound Alnylam sold a stake and control of development to the Medicines Company for $25 million.”If I knew then what we know now there’s no friggin’ way we would have licensed this out,” the Alnylam CEO told FierceBiotechnology.
Of course the future of the drug, along with all other PCSK9-related drugs and other novel LDL drugs, depends heavily on the results of the very large cardiovascular outcomes trial now underway with the PCSK9 inhibitors.
Speaking about the overall direction of the cholesterol market, Meanwell said that industry needs to show that expensive new drugs confer tangible value. “We don’t know what you save if you avoid a heart attack,” he said. “We’re going to have to be creative,” he said, and this may involve innovative models of payment that could involve “risk sharing.”
Meanwell said that some wild predictions about the cholesterol market are unrealistic. “That’s not going to happen,” said Meanwell, referring to a $150 billion nightmare scenario in which 10 million eligible patients receive PCSK9 inhibitors at a yearly cost of $15,000.
Meanwell also speculated about a “phase 5” study testing a strategy using the new drug to replace statins.
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