In controlling high cholesterol levels statins have reigned for a very long time, generating over $30 billion/year with products like Lipitor and crestor generating almost ten million/year each. Statins act by blocking HMG-CoA reductase, an enzyme required for the production of LDL, (the bad cholesterol) in the liver. Statins side effects could be severe. They can cause muscle damage. Some physicians believe they are overprescribed, as 30 million Americans currently take the cholesterol pills.
New breakthrough therapeutics that lower LDL (bad cholesterol) serum level, hence the risk of heart attacks probably as much as 70% are already in mid-phase trials, with some going to late phase trials. These breakthrough drugs, which are developed by Amgen (AMGN), Regeneron (REGN)/Sanofi, Pfizer and other firms block a protein expressed by the PCSK9 gene. This protein disables the capability of the liver cells to rid the blood from the dangerous cholesterol.
On November 15, Regeneron (REGN)/Sanofi and Amgen (AMGN) presented promising results from human trials at the American Heart association in Orlando, Florida. Amgen’s data were from an early study with the firm’s drug AMG145, a PCSK9 protein blocker. The study involved 54 men and two women -- 18 to 45 years old who were healthy and not taking other medications. The candidates received a single injection that contained one of five doses of AMG145, or a placebo, and their cholesterol was measured frequently for 85 to 113 days. The results were promising, demonstrating that the highest dose of the drug has successfully cut the LDL levels by 64 percent in healthy volunteers, compared with placebo injections.
Clapton Dias, a senior Amgen research executive who led the study stated that, "The more PCSK9 protein was lowered, the more bad cholesterol levels went down. With the higher doses, bad cholesterol stayed lower for a longer period."
Amgen said it is now conducting a similar study among adults who are already taking statins to control their cholesterol.
Regeneron’s/Sanofi’s drug REGN727 is more advanced than the other drugs. When REGN 727 was given at varying doses in combination with statins, it reduced LDL levels by further 30 percent to more than 65 percent. The patients have familial hypercholesterolemia, an inherited condition associated with very high LDL levels.
Regeneron has decided to conduct late Phase trials in the upcoming months. George Yancopoulos, Regeneron’s chief scientific officer said in a telephone interview, “The antibodies are really performing in a very exciting fashion. They seemingly do an even better job at sweeping the LDL out than existing medicines. It should be a big commercial opportunity.”
Pfizer, Merck & Co,/Alnylam Pharmaceuticals and Bristol-Myers Squibb in partnership with Isis Pharmaceuticals also have products developed through their proprietary technologies RNAi and antisense consecutively. They both aim at blocking the PCSK9 protein. If approved, the new products are expected to be used with statins for patients who do not achieve cholesterol-lowering goals with the statins alone. They would also be used on their own for a much smaller group who cannot tolerate statins.
This is great news for high cholesterol patients, cardiologists and the biotech developers. Amgen has already put a breakthrough drug denosumab on the market. The drug is marketed for two indications that have huge market under two trade names Prolia, for osteoporosis and Xgeva for the prevention or delay of cancer metastasis to bone.
Regeneron’s drug EyleaTM(aflibercept ophthalmic solution) has received unanimous recommendation for approval from the FDA Advisory Committee for wet macular degeneration. The drug is also submitted in Japan for Marketing Authorization for the treatment of Wet Age-Related Macular Degeneration. Eylea is expected to be approved for many other ocular indications, including diabetic macular edema and central retinal vein occlusion.
The firm has a marketed drug, Arcalyst® (rilonacept) Injection for Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. The same drug is expected to be granted approval for gout flare prevention.
Regeneron’s pipeline is full of promising products developed through its Trap technology for a variety of inflammatory diseases, cancers and other diseases. Most are breakthroughs, especially the anticholesterol drug REGN727 cited above. We believe Regeneron is on its way to become one of the most successful and prosperous top-tier biotech, heavy weight biotechnology firms.
The second Amgen?
We long both Amgen and regeneron.