With demand for its RNA interference meds booming, Alnylam Pharmaceuticals has commenced work to soup up its flagship manufacturing facility in Massachusetts.
Alnylam plans to spend $250 million in a bid to elevate its 200,000-square-foot facility in Norton, Massachusetts, as the biopharma industry’s first fully dedicated small interfering RNA (siRNA) enzymatic-ligation production plant, the Cambridge-based company said Dec. 17.
The project is expected to bolster capacity and reduce operating costs at the facility, which officially opened its doors for siRNA oligonucleotide bulk drug substance active pharmaceutical ingredient manufacturing back in 2021, according to Alnylam’s website. Online, Alnylam refers to the Norton site as its global production HQ.
Meanwhile, the enzymatic ligation tech at the heart of the undertaking is expected to buoy the launch of future Alnylam meds as the company increasingly aims its development engine at more widespread conditions.
The project revolves around siRELIS, Alnylam’s next-generation, scalable enzymatic ligation platform. The company contends that the platform builds RNAi therapeutics more efficiently by curbing material and plant resource requirements. The tech has the potential to “greatly” expand manufacturing capacity, which Alnylam argues makes “large-scale, sustainable production possible.”
In terms of how it works, the siRELIS (siRNA Enzymatic Ligation Synthesis) platform assembles short, high-quality RNA fragments—which Alnylam has dubbed “blockmers”—into complete molecules, under a process the company asserts is more efficient than traditional siRNA production methods.
The historic process for producing RNAi and other genetic medicines drug substance requires joining modified nucleosides to form sequences of nucleotides that make up the desired siRNA, Alnylam explained in a recent YouTube video. While effective, this process can take days and is inefficient for programs requiring larger amounts of drug substance or longer siRNA strands, the company pointed out.
SiRELIS, by contrast, synthesizes preformed nucleotide sequences that are then stitched together using enzymes.
Meanwhile, the FDA has also recognized the platform in its Emerging Technology Program, Alnylam noted in its announcement. SiRELIS has earned the distinction following the successful demonstration of Alnylam’s enzymatic ligation approach via pilot-scale batches of the experimental drugs zilebesiran, under development to reduce the risk of major cardiovascular events in patients with high blood pressure, and nucresiran, in development for transthyretin-mediated amyloidosis (ATTR), the company said.
“At this pivotal time with our expanding pipeline of RNAi therapeutics, Alnylam is accelerating development of siRNA manufacturing and changing what’s possible in a single facility,” Yvonne Greenstreet, M.D., Alnylam’s chief executive, said in a statement. “This advance will be a critical enabler in the scaling of our pipeline to include potential treatments for diseases such as hypertension, type 2 diabetes, and obesity.”
The expansion at the Norton plant is slated to boost both clinical and commercial supply of Alnylam’s siRNA oligonucleotide drug substance and will be used for supply of medications outside of the U.S. as well, the company noted in Wednesday’s release.
The drugmaker has already started construction on the project, with the expectation that the new capabilities will come online at the plant by late 2027. The expansion is also set to add an unspecified number of new jobs.
Alnylam has been on a hot streak this year, spurred on in no small part by the success of its rare heart disease drug Amvuttra, which was first approved in ATTR-polyneuropathy (ATTR-PN) in 2022 and picked up a key second green light in ATTR-cardiomyopathy (ATTR-CM) this past March.
Back in August, that performance was strong enough to lift Alnylam’s market cap above $50 billion, where it still stands today.
And, as of October, Amvuttra was still managing to eclipse Wall Street expectations. In the third quarter, Alnylam’s ATTR drug generated $685 million in sales, coming in 11% above analyst consensus estimates, according to a note from Jefferies at the time.
For the full year, Alnylam is now expecting total transthyretin amyloidosis franchise revenues to land between $2.475 billion and $2.525 billion.