Alnylam Scores Another RNAi Win with Mid-Phase IgAN Data

Alnylam CEO Yvonne Greenstreet, Courtesy of Alnylam Pharmaceuticals

Chalking up a mid-stage win for Alnylam‘s RNA interference (RNAi) portfolio, the Cambrige, MA-based company reported positive Phase II results Monday for cemdisiran, which is being developed to treat IgA nephropathy (IgAN).

The multi-center Phase II trial assessed the safety and efficacy of cemdisiran in 31 patients between 18 and 65 with IgAN. Anlylam found that cemdisiran was generally well tolerated with no adverse effects leading to additional treatment or discontinuation of the study.

One death occurred; however, it was found to be unrelated to the study.

Cemdisiran targets the C5 component of the complement pathway to RNAi. It is intended to treat diseases like IgAN by silencing mRNA, which is the genetic precursor to the disease pathway. It aims to prevent those pathways from being created in the first place. This slows, or may eventually stop, the progression of the disease, allowing the body to heal itself without the added stressor.

At week 32, the marker for the end of Phase II, cemdisiran demonstrated a clinically significant reduction in a 24-hour protein to creatine ratio, an indication of decreased inflammation and a recovering kidney. Spot urine data were consistent with 24-hour urine data, and the treatment’s effect appeared to begin as early as week eight.

“IgAN is an inflammatory disease that can lead to severe loss of kidney function. Thus, we, together with our partners at Regeneron, are working expeditiously to advance this investigational RNAi therapeutic into Phase III clinical development.” Sonalee Agarwal, Ph.D., vice president and program leader of the Cemdisiran program at Alnylam, said.

IgAN is the most common type of inflammatory disease that affects the glomerulus of the kidney. It impacts approximately 2.5 out of every 100,000 individuals per year, with the highest number of diagnoses coming from people in their 20s and 30s. One of the strongest risk factors is proteinuria, specifically if >1 g/day, with 20-40% of those patients progressing to end-stage kidney disease (ESKD).

While not fully understood, current data leads researchers to believe that IgAN is an autoimmune disease that might originate from an overproduction of aberrantly modified immunoglobulins (aka. antibodies). This overproduction leads to the promotion of inflammatory mediators, creating high levels of inflammation in the body.

Anlylam has been on the cutting edge of RNAi. Earlier this month, the company reported topline results from the Phase III APOLLO-B study of patisiran. The study showed that the therapeutic improved both functional capacity and quality of life in patients with transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy.

Across the globe, Silence Therapeutics in London, Sylentis in Madrid and Olix Pharmaceuticals in South Korea are developing RNAi therapeutics. Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals are also working to develop their own RNAi drugs in the United States.