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Tekmira Delays Clinical Trial for Cholesterol Drug as it Evaluates Alternative LNP Formulations

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This article has been updated from a version posted Sept. 10 to include comments made by a company official this week at an investor conference.

By Bernadette Toner

Tekmira last week announced that it has decided to delay a planned phase I/II clinical trial for its cholesterol drug TKM-apoB due to disappointing performance in non-clinical studies.

In a corporate update released on Friday, Tekmira said that in these studies, the performance characteristics of the compound's lipid nanoparticle formulation "have not met the company's expectations for the intended application."

The company noted that since it develops LNP formulations individually for each of its drug candidates, the delay in TKM-apoB will have "no impact" on any of its other drug programs or those of its collaboration partners, who include Alnylam, Roche, Takeda, and Pfizer.

Tekmira added that it has made "significant advances" in LNP formulation development and that it is considering "several alternative LNP formulations with improved characteristics" for TKM-ApoB development.

At the Rodman & Redshaw Healthcare conference held this week in New York, Mark Murray, president and CEO of Tekmira, said that the company expects "to be able to bring [TKM-ApoB] back into the clinic some time next year."

The drug, formerly called ApoB SNALP, is an siRNA designed to inhibit apolipoprotein B, a protein involved in cholesterol metabolism, and is being developed as a treatment for patients with high LDL cholesterol who do not respond to currently available treatments, such as statins. Murray said in his presentation, which was webcast, that approximately 10 percent of statin-eligible patients cannot tolerate these drugs.

"We think this represents a very interesting commercial opportunity to fill an unmet need to treat patients who need these drugs who are not currently served by current therapies," he said.

The delay is the second setback for the drug. In January, the company halted a phase I study of ApoB SNALP after a patient in the study experienced side effects associated with the drug's siRNA payload (GSN 1/14/2010).

To address the issue, the company used an improved screening assay to identify better apoB-targeting siRNAs. The planned I/II trial, which it expected to begin before the end of the year, was intended to evaluate the improved siRNA.

"We are not satisfied with the performance of our current TKM-ApoB LNP formulation for its intended use and we are going to focus on selecting an alternative formulation and availing ourselves of our existing improvements in formulation technology before resuming clinical development," Murray said in a statement last week.

At the Rodman & Renshaw conference, Murray told investors that the company has been "working to reformulate and bring back into the clinic an improved product, and what we're doing with this product is to introduce a new, more potent generation of lipids, so the product will have greater potency, and at the same time we're modifying the RNAi payload to prevent any unwanted immune stimulation."

TKM-PLK1 and TKM-Ebola

Tekmira last week also provided an update for two other drug candidates: its cancer drug TKM-PLK1 and the Ebola treatment TKM-Ebola.

TKM-PLK1 is based on an siRNA that silences polo-like kinase 1, a cell cycle protein that has been implicated as a target in several cancers, including colorectal, breast, non-small cell lung, and ovarian cancer.

Earlier last week, the company said that it had received clearance from the US Food and Drug Administration to begin phase I testing of TKM-PLK1 in patients with advanced solid tumors (GSN 9/9/2010). The company plans to begin the trial before the end of the year.

On Friday, the company said that it is also "evaluating opportunities" to expand the development of the drug, including a possible clinical trial in collaboration with the National Cancer Institute that would "aim to demonstrate PLK1 knockdown and RNAi activity in specific tumor types."

The additional trial "will provide an opportunity to evaluate TKM-PLK1 in a clinical trial designed to rapidly provide clinical data in an oncology application with Tekmira's LNP technology and confirm PLK1 as an important oncology target," the company said.

The company also provided a development timeline for TKM-Ebola, which it officially tapped as its third clinical candidate last month (GSN 8/19/2010).

Tekmira said last week that it expects to file an investigational new drug application with the US Food and Drug Administration for TKM-Ebola in the second half of 2011 and will initiate a phase I clinical trial at that time.

In July, the US Department of Defense awarded a contract worth up to $140 million to Tekmira to advance the TKM-Ebola program. The company said last week that the contract will support the program "through clinical development and FDA approval," and noted that the drug will be developed "under specific regulatory guidelines to advance therapeutics that cannot meet the requirements for traditional approval because human efficacy studies are not feasible."

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