FDA Approves UCB’s Complement Inhibitor for Generalized Myasthenia Gravis

FDA Entrance_iStock, Grandbrothers

Pictured: Exterior of the FDA building in Maryland/iStock, Grandbrothers

The FDA on Tuesday approved UCB’s zilucoplan, now to be marketed under the brand name Zilbrysq, for the treatment of generalized myasthenia gravis in patients who are positive for antibodies against the acetylcholine receptor.

Zilbrysq is the first once-daily subcutaneous targeted C5 complement inhibitor approved for generalized myasthenia gravis (gMG) and is currently the only once-daily target therapy for the rare autoimmune disease that patients can self-administer, according to UCB.

Zilbrysq is administered subcutaneously once-daily and its label carries a boxed warning for serious meningococcal infections. Life-threatening and fatal episodes of meningococcal infections have been observed in patients that have been treated with other complement inhibitors, the same drug class as Zilbrysq. There have been no instances of life-threatening or fatal meningococcal infections in Zilbrysq-treated patients to date.

Before administering the first dose, healthcare providers should first ensure that patients have complete or updated their vaccination at least two weeks prior, “unless the risk of delaying therapy outweighs the risk of developing a meningococcal infection,” according to Zilbrysq’s label.

Patients should still be monitored for the infection since they remain more vulnerable to Neisseria meningitidis even if they had developed antibodies in response to vaccination.

Samantha Masterson, CEO of the Myasthenia Gravis Foundation of America, called Tuesday’s approval of zilucoplan an “important development for the community.” Zilbrysq provides patients and physicians with an additional tool to treat gMG “in individualized ways that are the right fit for each individual patient,” Masterson said.

The chronic auto-immune disease arises when pathogenic antibodies attack certain proteins at the post-synaptic membrane, impairing signal transmission across the synapse.

The majority of gMG cases involve antibodies that target the acetylcholine receptor (AChR). These auto-antibodies activate the complement system and trigger the formation of the membrane attack complex, which eventually gets deposited on the neuromuscular junction. In turn, this damages the post-synaptic and overall reduces functional AChRs.

Zilbrysq is a peptide inhibitor of the C5 complement protein and prevents its cleavage into its two subunits, preventing the formation of the membrane attack complex. This mechanism of action allows Zilbrysq to avoid damage at the neuromuscular junction.

UCB backed its regulatory bid for Zilbrysq with data from the Phase III RAISE study, a randomized, double-blinded and placebo-controlled study that demonstrated “rapid, consistent and statistically significant” benefits in patients treated with the complement blocker versus placebo. RAISE also found a favorable safety profile for Zilbrysq.

Aside from Zilbrysq, UCB's gMG portfolio includes the monoclonal antibody rozanolixizumab, which works by binding to the human neonatal Fc receptor and blocks its interaction with IgGs. This activity allows rozanolixizumab to accelerate the breakdown of antibodies and lower the overall concentration of pathogenic autoantibodies.

In June 2023, the FDA approved rozanolixizumab for gMG, for which it is now being marketed under the brand name Rystiggo.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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