Understanding Cemdisiran's Mechanism of Action in Myasthenia Gravis

Complement inhibition has become an important therapeutic strategy in generalized myasthenia gravis (gMG), particularly for patients with acetylcholine receptor antibody-positive disease. By targeting complement C5, these therapies aim to reduce complement-mediated damage at the neuromuscular junction. Although existing C5 inhibitors act on circulating complement proteins, investigational approaches such as small interfering RNA (siRNA) offer a different method of reducing complement activity by suppressing protein production at its source.

In this NeurologyLive^® Special Report, Ali Habib, MD, a neuromuscular specialist at UCI Health, discusses emerging findings from the phase 3 NIMBLE trial (NCT05070858), which evaluated the investigational siRNA therapeutic cemdisiran in adults with gMG. The conversation was recorded during the 2026 AANEM Annual Meeting, held September 29 to October 2 in Orlando, Florida, where exploratory analyses examined hospitalization rates, myasthenic crises, and hospitalization duration among patients receiving cemdisiran compared with placebo.

In this opening episode, Habib provides background on cemdisiran's mechanism of action and the rationale for targeting complement C5 through RNA interference. He explains how the therapy acts at the liver, where C5 is produced, and what distinguishes this approach from currently available complement inhibitors. The discussion establishes the mechanistic foundation for understanding the investigational treatment and its potential role in gMG management.

Transcript edited for clarity.

Ali Habib, MD: Cemdisiran is a unique molecule being tested in the myasthenia gravis field. What's different about cemdisiran is not the target that it is impacting. The target is complement C5. It's the way that it is targeting it.

What's unique about cemdisiran is that it is a small interfering RNA, and it acts at the liver. So, the liver is the site where C5 is produced and put into circulation and gets into tissues.

The idea here is to limit that production from the liver with the use of cemdisiran, and that's what makes the approach novel compared with the other therapies that have already been put into use in myasthenia gravis targeting C5 inhibition.