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PCSK9 Drugs Are Here (and Way Over There)

By Brian Orelli, PhD - Sep 4, 2015 at 11:14AM

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As the first generation of the cholesterol-lowering drugs hits the market, investors should already be looking at the next-generation products.

The marketing battle over the newest drugs to lower cholesterol levels is on.

Source: Regeneron Pharmaceuticals.

Sanofi and Regeneron Pharmaceuticals' (REGN 0.20%) Praluent was approved by the Food and Drug Administration in late July, and Amgen's (AMGN 0.48%) Repatha followed suit with a thumbs-up from the agency last week.

Both drugs are antibodies targeting proprotein convertase subtilisin/kexin type 9, or PCSK9. The protein's job is to lower the amount of receptors responsible for taking low-density lipoprotein cholesterol, or LDL cholesterol, out of the bloodstream. Blocking PCSK9 increases the amount of LDL cholesterol receptors, which, in turn, lowers the patients' LDL cholesterol, that's the bad kind.

Neither Praluent nor Repatha are going to replace statins, such as Pfizer's (PFE -1.28%) Lipitor or AstraZeneca's Crestor. In fact, they're only approved for people that aren't getting enough benefit from statins and, when possible, are supposed to be used in combination with the drug class to help lower LDL cholesterol levels even further.

Source: Amgen.

The drugs will be used by patients with genetic mutations that cause them to have super high levels of cholesterol that often can't be helped by statins alone. Both drugs are approved for heterozygous familial hypercholesterolemia in which patients have one mutated copy of a gene that causes high levels of cholesterol while Repatha is also approved for the homozygous version of the disease where people have two mutated copies. Amgen estimates that 1 million people in the U.S. have either the heterozygous or homozygous form of familial hypercholesterolemia, but less than 1% are diagnosed.

Both drugs are also approved for patients with clinical atherosclerotic cardiovascular disease, which is a fancy way of saying a buildup of plaques in patients' arteries.

Let the marketing battle begin
Not surprisingly, since they target the same protein with an antibody, Praluent and Repatha have quite similar efficacies. In patients with heterozygous familial hypercholesterolemia, Praluent reduced LDL cholesterol between 36% and 59% compared to placebo, while Repatha had an average reduction in LDL cholesterol of approximately 60% compared to placebo.

Praluent was tested at two different concentrations, which explains the lower range. While the lower dose unsurprisingly doesn't work as well, some patients may not need a 60% reduction in their cholesterol levels, so the availability of a lower dose could give Sanofi and Regeneron Pharmaceuticals an advantage over Amgen.

Amgen has the advantage of having tested Repatha in homozygous familial hypercholesterolemia patients, but Sanofi and Regeneron Pharmaceuticals may not be passing much up by not going after that segment; Aegerion Pharmaceuticals is only predicting 2015 sales around $200 million for Juxtapid, which it sells to treat homozygous familial hypercholesterolemia.

New kids on the block
Pfizer
(PFE -1.28%) is on the tail of Sanofi, Regeneron Pharmaceuticals, and Amgen with its own PCSK9 antibody that still goes by its generic name bococizumab. All of the phase 3 trials testing the drug are still recruiting patients according to clinicaltrials.gov, so the drug won't be on the market anytime soon.

More intriguing than bococizumab, Pfizer has indicated that it's working on an oral inhibitor of PCSK9. Being antibodies, Repatha, Praluent, and bococizumab have to be injected. Certainly for some patients scared of injecting themselves, a pill will be a welcome choice.

But keep in mind that Repatha and Praluent are only dosed every two weeks -- and Repatha can also be dosed once a month, albeit a larger dose that requires three injections -- so the injections might be more convenient for some people since they eliminate the need to remember to take a pill daily, assuming that's the dose Pfizer oral drug works out.

Sticking with the less is more theme, Alnylam Pharmaceuticals (ALNY 1.67%) and The Medicines Company (MDCO) released data last weekend from a phase 1 trial that showed its RNAi PCSK9 drug, ALN-PCSsc, produced a mean maximum reduction in LDL cholesterol levels of 64%. Interestingly, after just one dose of ALN-PCSsc, mean knockdowns of 39% to 44% were seen at various doses 140 days after the injection. The long-lasting drug could support quarterly or even bi-annual injections.

Whether Alnylam Pharmaceuticals and The Medicines Company can supplant Sanofi, Regeneron Pharmaceuticals, and Amgen remains to be seen, however. The duo is ready to start a phase 2 study by the end of the year, but that means a phase 3 trial won't start until 2017. Even with the more convenient dosing, it's hard to know how much market Alnylam Pharmaceuticals and The Medicines Company can take from drugs after they've been on the market for four or more years.

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Stocks Mentioned

Pfizer Inc. Stock Quote
Pfizer Inc.
PFE
$51.64 (-1.28%) $0.67
Amgen Inc. Stock Quote
Amgen Inc.
AMGN
$246.73 (0.48%) $1.18
Regeneron Pharmaceuticals, Inc. Stock Quote
Regeneron Pharmaceuticals, Inc.
REGN
$596.56 (0.20%) $1.16
Alnylam Pharmaceuticals, Inc. Stock Quote
Alnylam Pharmaceuticals, Inc.
ALNY
$150.73 (1.67%) $2.48
The Medicines Company Stock Quote
The Medicines Company
MDCO

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