An experimental injection that is at least five years from the market dramatically lowered cholesterol for as much as 140 days in an early clinical trial to be presented in London at the annual meeting of the European Society of Cardiology. The data raise expectations for the drug’s makers, Alnylam Pharmaceuticals and The Medicines Company.
Since July, the U.S. Food and Drug Administration has approved two biotechnology drugs that dramatically lower cholesterol levels. Their makers hope – and insurers fear – that these medicines could become the industry’s next big sellers.
The first, Praluent from Regeneron and the drug giant Sanofi, is given once every two weeks. The second, Amgen’s Repatha, which was approved last week, is also given on a twice-monthly schedule, although it is also possible to deliver it in a single, big dose once a month. Despite the fact that both are shots, not pills, and that neither has been proved to prevent heart attacks or strokes yet, the excitement about them is considerable because they can lower low-density lipoprotein (LDL), the so-called “bad cholesterol,” by 60%.
Praluent and Repatha both work by blocking a protein called PCSK9. The new drug from Alnylam and The Medicines Co. uses a new technology to block the PCSK9 gene. The drug is called ALN-PCS. Normally a medicine so far behind would have little hope of garnering significant sales (Pfizer also has a PCSK9 drug approaching the market) but Alnylam and The Medicines Co. say they hope that a drug that could be given just four times a year – or maybe even just twice – could become a big seller. “You could go to your physician and get a cholesterol check and a dose of drug at the same timeframe at your physician,” says Clive Meanwell, The Medicines Company’s chief executive.
The data being presented back that up. Twenty-four patients were assigned to either receive placebo or one of five doses of ALN-PCS ranging from 25 milligrams to 800 mg. Those who received doses of at least 100 mg saw their LDL drop at least 40%; it dropped as much as 78% at the 500 mg dose. More impressively, 140 days after the treatment was given, patients still had an average LDL reduction of about 40%.
The study also gave 45 subjects multiple doses of either ALN-PCS or placebo. These patients had maximal LDL reductions of 80% and average LDL reductions of 50% to 60%, roughly equivalent to Praluent and Repatha. So far, the drug appears to be safe. One patient had elevated liver enzymes, the companies said, but that appeared to be due to the cholesterol pill the patient was taking.
There is still a lot that could go wrong. The makers of Praluent and Repatha are conducting big studies to prove that the drugs prevent heart attacks and strokes. Meanwell says he does not think this will be necessary for ALN-PCS. But given that the drug is an entirely new type of medicine that works by affecting the messages sent from genes to the machinery of cells, the FDA might want this data. Any side effect that does occur in a long-acting drug will be a bigger concern, given that a patient can’t stop taking it.
Alnylam’s Chief Executive, John Maraganore, argues that the drug is likely to be safe because we know that people with defective versions of the PCSK9 gene not only do well, but thrive, living healthy lives with very low cholesterol levels. He says ALN-PCS works only in the liver, where cholesterol made, which could even make side effects less likely. “Our view is it would be pretty transformative for the whole field,” he says.
The product is important for the stocks of both companies. The Medicines Company has a market capitalization of $2.3 billion; Alnylam has a market cap of $9.2 billion.
