Alnylam posts positive PhI for RNAi cholesterol drug

Alnylam ($ALNY) is pushing its latest RNAi drug through early clinical trials, highlighting the company's delivery platform that enables an effective gene-silencing treatment. This time, the RNA specialist published results from a successful Phase I study of its cholesterol drug ALN-PCS.

ALN-PCS is designed to target the gene coding for the enzyme PCSK9, short for proprotein convertase subtilisin/kexin type 9, which metabolizes "bad" cholesterol, or low-density lipoprotein (LDL) cholesterol. By lowering levels of the enzyme, the silencing of this gene increases LDL receptor levels in the liver, lowering cholesterol levels in the bloodstream, Alnylam's senior director of research Kevin Fitzgerald told FierceDrugDelivery.

"An RNAi-based therapy could potentially provide a new treatment option for patients who can't control their high cholesterol with existing treatments, like statins, or diet alone," Fitzgerald said. "Severe hypercholesterolemia is estimated to affect more than 500,000 patients worldwide."

In the Phase I trial, results of which Alnylam published in the journal The Lancet, a single subcutaneous dose showed an 84% knockdown of PCSK9 in blood plasma. In earlier animal trials, this cut LDL cholesterol levels by more than half. The company also showed that the drug didn't impair liver function and had no effect on levels of "good" cholesterol.

The delivery of RNAi drugs, discovered in the mid-2000s, has proven difficult, mostly due to the fragility of the complex molecules. But Alnylam's GalNAc-siRNA platform has shown time and time again in recent years to be an effective solution. The sugar molecule GalNAc conjugates to the RNA molecule to enable the subcutaneous delivery.

"In the early years of developing RNAi therapeutics, a challenge to the viability of RNAi as a therapeutic modality was delivery--i.e., getting the siRNA into the cell so that it could trigger the RNAi mechanism," Fitzgerald said. "In more recent years, though, a tremendous amount of progress has been made in this area. Alnylam has been at the forefront of this progress; we have developed a robust drug discovery platform to silence any target gene expressed in the liver."

Alnylam has several other RNA-based treatments using the delivery method, and the company hopes to have 5 of them in clinical development by 2015. The next step for ALN-PCS is to conduct larger multidose studies without premedication, Fitzgerald said. Alnylam teamed up with The Medicines Company ($MDCO) for the Phase I trial and will continue the partnership through Phase II, he noted.

Also this week, The Motley Fool took a look at whether Alnylam is a sound investment based on its early stages and a 250% stock gain in the last year, concluding that the company still has room to grow.

- read the Lancet paper
- here's the release
- and here's Motley Fool's report

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