Key takeaways:

• If approved, cemdisiran could be offered to treat gMG subcutaneously with dosing every 3 months.
• Clinical trial results showed meaningful improvements in activities affected by gMG, such as eating and talking.

Cemdisiran, a potential new drug for the treatment of generalized myasthenia gravis, has been accepted for priority review by the FDA and the European Medicines Agency, according to officials with Regeneron Pharmaceuticals.

If approved, cemdisiran would be the first small interfering RNA (siRNA) treatment for generalized myasthenia gravis, a chronic autoimmune disorder, and the only therapy to be offered subcutaneously with four doses needed annually, said Tuan Vu, MD, professor of neurology at the University of South Florida Morsani College of Medicine.

Data derived from press release.

“While current therapies have mitigated disease activity in many patients, unmet needs remain as disease control is hard to achieve and then maintain in some individuals, leading to their having frequent hospital visits, inconsistent symptom control, and lack of durable treatment effects that can degrade their quality of life and complicate long-term disease management,” Vu told Healio.

GMG affects the immune system, causing abnormal anti-acetylcholine receptor (AChR) antibodies such as complement factor 5 (C5) to activate the complement system, disrupting communication between nerves and muscles, according to the release. It can have debilitating effects on daily functions, such as talking, eating, breathing, vision and mobility, Vu said.

Cemdisiran would be used to treat adult patients who are anti-AChR antibody-positive by inhibiting terminal complement activation in a novel way, Vu said.

“Rather than directly blocking the C5 protein, cemdisiran is an investigational siRNA therapy designed to greatly reduce the production of C5 available for complement activation,” Vu said. “By lowering complement activity, cemdisiran selectively controls the underlying mechanisms that contribute to gMG without broadly suppressing the immune system.”

Trial results

The submission to the FDA and European Medicines Agency (EMA) followed the phase 3 NIMBLE trial evaluating cemdisiran’s safety and efficacy, according to the release.

Participants in the trial, the results of which were published in The Lancet, were separated into placebo (n = 59) and cemdisiran-treated (n = 64) groups. The group treated with cemdisiran was given subcutaneous treatment every 12 weeks and experienced clinically meaningful improvements within 2 weeks, researchers reported.

On the Myasthenia Gravis-Activities of Daily Living scale, which measures changes from baseline in daily functions affected by gMG, such as eating and talking, participants in the cemdisiran-treated group experienced a placebo-adjusted improvement of 2.3 points (P < 0.001) after 24 weeks.

On the Quantitative Myasthenia Gravis scale, which measures changes from baseline in muscle function, the cemdisiran-treated group saw a placebo-adjustment improvement of 2.8 points (P = 0.002).

“These improvements deepened over time across both scales and were sustained through week 24, with no indication of waning efficacy between doses,” Vu said.

Moving forward

GMG is estimated to affect 150 to 200 people for every million people worldwide, including roughly 85,000 people in the U.S., according to the release.

The FDA accepted cemdisiran for a New Drug Application under priority review with a target action date of November, according to the release. The EMA is expected to make a decision on the drug in the second half of 2027.

Currently approved C5-inhibiting gMG treatments have dosing schedules ranging from daily subcutaneous injections to IV infusions every 2 months, Vu said. The 3-month dosing schedule of cemdisiran would represent a reduced treatment burden, he said.

As an siRNA, cemdisiran is also not expected to affect the pharmacokinetics of other commonly used gMG treatments, Vu said.

For more information:

Tuan Vu, MD, can be reached at neurology@healio.com.