Skip to main content
Premium Trial:

Request an Annual Quote

Unveiling New Strategy, Alnylam Aims to Debut Five Clinical Candidates by 2015

Premium

By Doug Macron

Alnylam Pharmaceuticals this week announced a plan to have five RNAi drug programs in the clinic by 2015, including its phase I transthyretin-mediated amyloidosis treatment, ALN-TTR01.

The company also disclosed that it and partner Cubist Pharmaceuticals have decided to put on hold the development of a second-generation version of Alnylam's respiratory syncytial virus treatment, although no details regarding the decision were provided.

According to Alnylam, the so-called Alnylam 5x15 plan will focus the company's attention on product candidates against "genetically defined target and disease … [with the] potential to have a major impact in a high unmet need population." Notably, Alnylam said it plans to commercialize these drugs in the US on its own.

The candidates will also "leverage the existing Alnylam delivery platform; [provide] the opportunity to monitor an early biomarker in phase I trials for human proof of concept; and [offer] clinically relevant endpoints for the filing of a new drug application with a focused patient database and possible accelerated paths for commercialization."

First in line under the strategy is the ALN-TTR program, the first candidate from which has been fast-tracked and is expected to complete phase I testing in the first half of this year. Alnylam said it is also advancing ALN-TTR02, which uses a second-generation delivery technology, with an eye toward filing an investigational new drug application before year end.

Alnylam expects the ALN-TTR program to enter phase II next year.

The company said the Alnylam 5x15 initiative will also include its preclinical hypercholesterolemia drug ALN-PCS, which targets proprotein convertase subtilisn/kexin type 9 and had been expected to move into human testing this year; and ALN-HPN, a new candidate that inhibits hepcidin, a gene related to iron homeostasis, as a treatment for refractory anemia.

On top of this, the Alnylam 5x15 plan will involve two other drug programs that will be unveiled later in 2011, the firm said.

Alnylam said that it aims to commercialize drugs from all five programs in the US on its own, although marketing allies may be sought in other territories. The decision marks a significant shift in strategy for the company, which had long made finding big pharma/biotech partners for its product candidates a key goal.

However, partnering has become a significant challenge for companies playing in the therapeutic RNAi space over the past two years, with a number of firms missing collaboration guidance in 2010 (GSN 1/6/2011).

Alnylam has been particularly vulnerable to the growing skepticism over RNAi by larger biopharmaceutical companies in recent months.

In November, Alnylam's long-time partner Novartis announced that it would not exercise an option to acquire broad, non-exclusive access to the RNAi drug shop's intellectual property and technologies — a transaction that would have been worth $100 million to Alnylam (GSN 9/30/2010).

A few months later, partner Roche said that it would discontinue all of its in-house RNAi operations amid a wide-scale cost-cutting initiative (GSN 11/18/2010).

And this week, Alnylam revealed that its RSV deal with Cubist may be in jeopardy.

In early 2009, Cubist took the rights to the RSV therapy ALN-RSV01 in all markets outside of Asia as part of a 50/50 joint-development and profit-sharing deal (GSN 1/19/2009).

After completing a phase II study in adult lung-transplant patients naturally infected with the virus, Cubist decided to step back from ALN-RSV01 in order to focus on a follow-on candidate, ALN-RSV02, being developed for the more lucrative population of pediatric RSV patients (GSN 11/12/2009).

This week, however, Alnylam said the partners have decided to shelve ALN-RSV02. However, development of ALN-RSV01, to which Cubist maintains the opt-in rights, will proceed. Phase II data on the agent is expected in 2012.

Despite the change in partnering strategy, Alnylam said that it will continue to look to collaborate on its phase I cancer drug ALN-VSP before moving it into phase II development. Its preclinical Huntington's disease effort, which is already partnered with Medtronic, remains on track for an IND filing in 2012.


Have topics you'd like to see covered in Gene Silencing News? Contact the editor
at dmacron [at] genomeweb [.] com.

The Scan

Push Toward Approval

The Wall Street Journal reports the US Food and Drug Administration is under pressure to grant full approval to SARS-CoV-2 vaccines.

Deer Exposure

About 40 percent of deer in a handful of US states carry antibodies to SARS-CoV-2, according to Nature News.

Millions But Not Enough

NPR reports the US is set to send 110 million SARS-CoV-2 vaccine doses abroad, but that billions are needed.

PNAS Papers on CRISPR-Edited Cancer Models, Multiple Sclerosis Neuroinflammation, Parasitic Wasps

In PNAS this week: gene-editing approach for developing cancer models, role of extracellular proteins in multiple sclerosis, and more.