Skip to main content
Premium Trial:

Request an Annual Quote

With New Strategy, Alnylam Again Shuffles Its Pipeline


This article has been updated to clarify Alnylam's partnership with Medtronic and statements regarding its liver cancer program.

By Doug Macron

When Alnylam Pharmaceuticals announced last week its latest product-development strategy, it said it reflected a shift of its focus onto "genetically defined diseases" offering the potential for "early commercialization opportunities."

It also marked the latest in a series of pipeline changeups the company has undertaken since it was founded in 2002.

Alnylam's new initiative, which it calls Alnylam 5x15, promises five RNAi drug programs in "advanced clinical development" by 2015 (GSN 1/6/2011). Included is the company's phase I transthyretin-mediated amyloidosis effort, slated to enter phase II testing next year; as well as preclinical programs in hypercholesterolemia and refractory anemia.

Two other Alnylam 5x15-related programs will be unveiled later this year, the company said.

"As part of our … strategy, we have made portfolio decisions to focus our investments in our highest-value activities and on programs with exciting potential for addressing major unmet medical needs," Alnylam President and COO Barry Greene said in a statement last week.

But this is not the first time Alnylam has shuffled its pipeline.

As early as 2003, the company was exploring Parkinson's disease through a collaboration with the Mayo Clinic (GSN 10/31/2003).

Under that arrangement, Alnylam provided Mayo with RNAi-based drug compounds that knock down alpha synuclein expression for testing in in vitro and in vivo experiments, as well as research funding. At the time, Alnylam CEO John Maraganore told Gene Silencing News that Alnylam aimed to work with a medical device partner to move the Parkinson's program into the clinic.

By early 2005, Alnylam had found that partner in Medtronic (GSN 2/11/2005), and in late 2006 the firm presented promising data at the Society for Neuroscience's annual meeting (GSN 10/19/2006).

However, in mid-2007, Alnylam and Medtronic announced that they had narrowed the focus of their alliance to Huntington's disease(GSN 8/2/2007).

Another program that had once been on the top of Alnylam's radar was a fledgling effort in influenza.

The company first started working on the disease in 2005, collaborating with researchers from the University of Georgia to "discover and develop a directly administered RNAi-based drug for the prevention and treatment of respiratory infection from newly emerging, highly pathogenic strains of influenza virus," it said at the time (GSN 5/27/2005).

Later that year, Alnylam said that it had added pandemic influenza to its formal drug-development pipeline, and was aiming at filing an investigational new drug application for a flu treatment "as early as the end of 2006," after securing funding from the US government (GSN 12/16/2005).

By mid-2007, however, Alnylam hadn't met its IND goal and said that the flu program was facing indefinite delays amid shrinking interest in “novel treatments for pandemic flu” from the federal government and “the need for optimized formulations to achieve the necessary level of in vivo efficacy," Greene said at the time (GSN 8/16/2007).

“We have just not been satisfied with the level of in vivo efficacy we’re seeing related to specific RNAi effects,” Maraganore added in 2007. Alnylam has not provided significant details on the flu program since then, and it is no longer listed on its publicly available pipeline.

[ pagebreak ]

Experiencing a similar fate was Alnylam's one-time program in wet age-related macular degeneration.

Considered low-hanging fruit for the RNAi drugs space given the ease with which siRNAs can be administered into the eye, AMD was a focus for a number of companies in the space. Alnylam's foray into the disease began in earnest in 2004 through its now-terminated alliance with Merck (GSN 7/2/2004).

About a year later, however, Maraganore indicated that Alnylam was considering dropping the program, largely because of strong clinical data supporting an antibody-based AMD treatment under development by Genentech (GSN 8/5/2005). That drug, Lucentis, has since been approved for the disease.

Notably, Alnylam at this time had just formed a major partnership with Novartis, which collaborated with Genentech on Lucentis, putting its AMD program in direct competition with that of an ally.

A few months later, Alnylam withdraw from the AMD field, instead re-focusing its efforts on a treatment for respiratory syncytial virus, which is now in phase II testing (GSN 9/23/2005).

Another of Alnylam's early drug programs to be shelved was its bid to knock down apolipoprotein B, a protein associated with cholesterol metabolism, as a treatment for hypercholesterolemia.

In 2004, the firm published data showing that intravenously delivered siRNAs could knock down apoB in rats, but Maraganore at the time noted that the program wasn't a part of Alnylam's official pipeline (GSN 11/12/2004).

In 2006, the company put the apoB program on hold in order to focus on another cholesterol target, proprotein convertase subtilisn/kexin type 9, which is the foundation of its current hypercholerolemia initiative (GSN 12/7/2006). At the time, company officials said that while apoB served as a good model to prove the efficacy of RNAi in vivo, PCSK9 was a superior target.

On the Ropes?

In announcing the Alnylam 5x15 initiative, the company also raised questions about the status of two other ongoing programs.

Last week, Alnylam said that it and partner Cubist Pharmaceuticals have decided to stop work on a second-generation version of the RNAi shop's RSV drug, which was being developed for use in pediatric populations.

Previously, Cubist had held the rights to the first-generation version, ALN-RSV01, being tested in phase II in adult lung transplant patients, but later decided to focus on the newer compound, ALN-RSV02.

Now, Alnylam said, it will only move forward with ALN-RSV01, which Cubist has the option to co-develop.

Alnylam also indicated last week that it may not move into later-stage development with its phase I liver cancer drug ALN-VSP.

The company said it intends to begin phase II studies of the agent if it finds a partner for the program, but did not specify the future of the program if it goes unpartnered.

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