AAN 2026: Expert Insight on Cemdisiran’s Role in Simplifying gMG Care Through Subcutaneous Quarterly Dosing

In an interview with Pharmacy Times, highlighting his conversation at the 2026 American Academy of Neurology (AAN) Annual Meeting, Tuan Vu, MD, a professor in the Department of Neurology at USF Health in Tampa, Florida, explains that cemdisiran represents a completely novel mechanism of action in generalized myasthenia gravis (gMG)—targeting C5 messenger RNA to reduce the quantity of C5 protein available for complement activation, rather than blocking the C5 protein itself, and enabling subcutaneous administration once every 3 months.

Vu addresses findings from the phase 3 NIMBLE trial (NCT05070858), noting that cemdisiran monotherapy achieved approximately 77% complement inhibition and matched or outperformed combination therapy on nearly every clinical end point, which he attributes to a therapeutic threshold effect in which reducing complement activity sufficiently—rather than eliminating it completely—is enough to restore clinical function, an effect also observed with FcRn inhibitors and other upstream therapies.

Pharmacy Times: Can you introduce yourself and explain your current role?

Tuan Vu, MD: Hi. My name is Tuan Vu. I’m a professor of neurology at the University of South Florida in Tampa. I spend my professional time conducting clinical trials, particularly in myasthenia gravis, and I also see patients and teach clinical neurophysiology fellows.

Pharmacy Times: Cemdisiran targets C5 messenger RNA rather than the C5 protein itself. How does that translate into a different dosing experience for patients compared with currently approved complement inhibitors in gMG?

Vu: It is a completely novel mechanism of action. Instead of blocking the effect of C5 on the postsynaptic membrane, cemdisiran actually reduces the production of C5 available for complement activation. Because of how it works, it can be administered subcutaneously once every 3 months, which considerably reduces treatment burden across the board.

Pharmacy Times: Cemdisiran monotherapy achieved about 77% complement inhibition, yet it matched or outperformed the combination arm on nearly every clinical end point. What do you make of that finding?

Vu: This is a completely novel mechanism of action. It reduces the quantity of C5 available for the complement cascade, rather than blocking C5 itself. Based on our results, the efficacy is really quite good. We cannot directly compare it to other C5 inhibitors, mainly because the study designs and patient populations differ. The question is, why would we see this level of efficacy when blocking only about 70-some percent of activity? I think there is a threshold beyond which you achieve a clinical effect. If you lower complement activity below that threshold, you can regain function—you do not have to block it 100% of the time.

Supporting evidence for this comes from looking at FcRn inhibitors, where antibody levels are reduced to about 30% to 40% residual, so antibodies are still present, yet efficacy is still observed. Similarly, upstream therapies that act analogously to FcRn inhibitors in reducing antibody production show clinical effect without driving levels to zero. That brings me back to my original point: If you reduce complement activity sufficiently below the threshold, you can achieve clinical efficacy.

Pharmacy Times: Meningococcal infection risk is something pharmacists routinely counsel patients on with C5 inhibitors. What did NIMBLE show on that front, and does cemdisiran’s safety profile change that conversation at all?

Vu: It is always a concern. The complement cascade is what we rely on to fight encapsulated bacteria, and blocking it increases the risk of meningococcal meningitis. As discussed, cemdisiran does not block complement completely, so perhaps that provides some degree of protection over time. The study is fairly short, however, so we do not know what the long-term effect will look like over years—that remains to be seen. I do think that for anything involving C5, proper vaccination is still required.

Pharmacy Times: With dosing only every 3 months subcutaneously, how significant is the treatment burden reduction compared with what patients are currently on?

Vu: We currently have 3 C5 inhibitors on the market, and dosing ranges from daily subcutaneous injections to IV [intravenous] infusions every 2 weeks or every 2 months. Having the option of a subcutaneous injection once every 3 months—which would take just a few minutes at most—would definitely represent a meaningful reduction in treatment burden.

Pharmacy Times: Where do you see cemdisiran fitting into the gMG treatment landscape if approved?

Vu: That is actually a tough question. We do not have any medication that works 100% across the board for everyone, so the decision of what to choose and how to treat still relies on the interaction, conversation, and shared decision-making process between the doctor and the patient. This medication does have clear advantages—low treatment burden and fairly high efficacy. At the moment, we do not have biomarkers to determine who will respond best to which therapy, but cemdisiran is definitely one treatment we now have available, and that is a conversation we must have with patients. To be honest, in MG treatment, you often do not know until you try, because we have no markers to guide us.