Skip to main content
Premium Trial:

Request an Annual Quote

Roche Using SNALPs with First RNAi Rx Candidate, Optimizing In-House Delivery Tech


By Doug Macron

A top Roche official confirmed this week that the company will file its first investigational new drug application for an siRNA therapeutic in 2010, and that the agent will be delivered using Tekmira Pharmaceuticals' stable nucleic acid lipid particles, rather than an in-house delivery technology.

Meanwhile, the Swiss drugs and diagnostics giant is taking a measured approach to the related but nascent microRNA field, exploring partnerships with key miRNA companies and doing a certain amount of research on its own, yet keeping most of its attention focused on RNAi, Lou Renzetti, global head of RNA therapeutics for Roche, told RNAi News.

One of the biggest pharmas playing in the RNAi space, Roche has long expected to advance its first drug based on the gene-silencing technology into human trials next year (see RNAi News, 2/14/2008).

Having acquired in 2007 the Kulmbach, Germany-based operations of Alnylam Pharmaceuticals — another Tekmira partner — as part of a broad drug-discovery and -development deal (see RNAi News, 7/12/2007), it was not unexpected that Roche's first RNAi drug would be siRNA-based.

Although Roche licensed Tekmira's SNALPs less than a year later (see RNAi News, 4/3/2008), its $125 million acquisition of Mirus Bio and its dynamic polyconjugate delivery technology in July 2008 suggested that the company was making its in-house portfolio of delivery solutions a priority.

And while Roche is focused on its own delivery technologies, being "first and best in class" is a top goal, Renzetti said. Using SNALPs with its first siRNA drug "would give us a chance to get a first-in-human study [underway], monitor target knockdown," and examine pharmacokinetics and pharmacodynamics.

Indeed, with SNALPs having already been administered, albeit to a limited degree, to humans — Tekmira recently began a phase I study of a SNALP-delivered siRNA drug for hypercholesterolemia (see RNAi News, 7/9/7009), just a few months after Alnylam began a phase I study of a liver cancer drug that incorporates the technology (see RNAi News, 4/9/2009) — the trail to the clinic has already been blazed for Roche.

The company could still evaluate the DPCs in humans in the relatively near future, possibly even with its lead RNAi drug candidate, but as it stands now, it is in the process of optimizing the delivery technology, since "we do not wish to take a first-generation DPC into the clinic," he noted.

At the same time, with DPCs, "we have evidence … of active targeting," Renzetti added. "So the question becomes, 'Which target cells would we like to go after for proof of concept?'" The additional optimization work would help establish that, he said.

[ pagebreak ]

Overall, Roche believes that the development of multiple RNAi drugs will require multiple delivery approaches, and "one challenge we're all going to face is the extrapolation to humans with these different delivery modules," Renzetti said. As such, just getting into the clinic is key because the data, "even if they were something that were not quite optimal … will be critical."

Renzetti noted that Roche is currently preparing for a pre-IND meeting with the US Food and Drug Administration, but declined to provide specific details about the siRNA drug candidate or its clinical-development plan.

He also declined to comment on additional RNAi programs in the pipeline, but noted that Roche's interests in the space continue to center around liver-associated metabolic diseases, respiratory disorders, and cancer.


In early 2008, Lee Babiss, former global head of pharma research at Roche, told RNAi News that the company was in talks about a possible miRNA drugs collaboration with an undisclosed company and that it was conducting "preliminary" research on agents targeting the small, non-coding RNAs.

This week, Renzetti said that Roche continues to monitor the field, and while it may not have actually consummated any kind of alliance, it did recently hold a partnering meeting with "several" unnamed miRNA companies.

"It's an exciting, evolving area … you just have to decide when to jump in," Renzetti said. "We also have to be careful that we don't distract ourselves from our primary effort right now in the siRNA space.

"There is going to be a time when we place a bet" on miRNA therapeutics, he added. Still, "we already placed one bet in the siRNA and delivery area," and the trick will be balancing the two.

Leading Roche to be a little cautious about miRNAs is the fact that their effects are so widespread, he noted.

With siRNAs, "you're looking at modulation of a single gene product or modulating several gene products very selectively," Renzetti explained. But with miRNAs, "when you modulate one, whether [with] agonists or antagonists, the consequences are not really known … [and] that's always the concern."

And that concern also extends to the diagnostic space, where miRNAs have already proven themselves to a certain degree with the commercialization of tests by Rosetta Genomics and Asuragen.

As one of the biggest diagnostic firms in the world, Roche is also weighing the potential to use miRNAs as biomarkers in various contexts, Renzetti said. "But again, when these things are changed within the cellular environment, do we understand enough about these that we can then make those claims?"