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As Alnylam Files to Begin Testing Cholesterol Drug in Humans, Questions Linger Over Delivery Tech


By Doug Macron

Alnylam Pharmaceuticals this week announced that it has filed the necessary application to begin phase I testing of its siRNA-based hypercholesterolemia drug ALN-PCS in the UK, and said that it expects to report data from the study by the end of the year.

Notably, Alnylam said that the drug candidate is the first to incorporate the company's second-generation lipid nanoparticle technology. However, Alnylam is currently embroiled in a lawsuit with partner Tekmira Pharmaceuticals over ownership of that very delivery technology.

ALN-PCS comprises siRNAs against proprotein convertase subtilisn/kexin type 9, which has been shown to regulate low-density lipoprotein receptor levels and play a role in plasma LDL clearance (GSN 5/14/2009).

Alnylam had long been a close partner of Tekmira's, using its proprietary lipid delivery technology in a number of its drug candidates including the phase I liver cancer treatment ALN-VSP02 and mentioning the company as a contributor to the ALN-PCS program.

But in its announcement this week, the company said that the cholesterol drug would use a “proprietary Alnylam second-generation lipid nanoparticle technology” called MC3.

Whether that technology is actually proprietary, however, is currently the subject of a lawsuit.

Earlier this year, Tekmira sued Alnylam for allegedly misusing trade secrets related to its lipid-based delivery technologies (GSN 3/17/2011).

“Alnylam abused its collaborator status and access to [the] confidential information by improperly using this information for its own internal purposes and to replicate a competing technology in ways that were unauthorized and without our consent,” Tekmira President and CEO Mark Murray said at the time during a conference call held to discuss the lawsuit.

Specifically, Tekmira alleges that Alnylam used its knowledge of the lipid used with ALN-VSP02 to develop unauthorized, next-generation formulations, including MC3.

“Alnylam stole MC3 from Tekmira,” the lawsuit charges.

Alnylam responded with a countersuit, charging Tekmira with, among other things, the failure to observe “confidential and non-public alternative dispute resolution procedures” required by the companies' agreements (GSN 4/7/2011).

Early last month, Tekmira expanded its suit to include AlCana Technologies, a Canadian startup and close Alnylam collaborator that employs a number of scientists who had previously worked for Tekmira (GSN 6/9/2011). In court filings, Tekmira also said that it was the one that had been developing MC3 and confidentially disclosed details about the technology to Alnylam pursuant to their partnership arrangements.

Alnylam “misused those trade secrets by, among other things, filing for patents in its own name, and without including any Tekmira inventors, on a lipid structure that was broad enough to include the MC class,” Tekmira claims.

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A few weeks later, Alnylam responded with its own accusations of trade-secret misappropriation, alleging that MC3 was discovered at AlCana and that Tekmira passed on the opportunity to acquire a stake in the technology after misjudging its value (GSN 6/30/2011).

Now, Tekmira has turned to “litigation in the hope that it can somehow reverse its prior business decision,” Alnylam stated.

A spokesperson for Alnylam said this week that Tekmira “provided the manufacturing services” for ALN-PCS pursuant to the companies' agreements, but reiterated that the MC3 delivery technology is Alnylam's own.

The Trial

Alnylam said that it filed a clinical trial application with the UK's Medicines and Healthcare Products Regulatory Agency, and that upon receiving clearance, it will begin phase I testing of the product.

The placebo-controlled study is designed to test a single ascending dose of ALN-PCS in approximately 32 healthy volunteers with elevated baseline LDL levels.

Patients will be enrolled into “five sequential cohorts of increasing doses ranging from 0.015 to 0.25 mg/kg,” the company said.

Primary endpoints are safety and tolerability. Secondary objectives include characterization of plasma and urine pharmacokinetics, and the assessment of pharmacodynamic effects of the drug on plasma PCSK9 protein and LDL cholesterol levels as measured from serial blood samples taken before and after dosing.

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