Japan approves zilucoplan, Rystiggo for adults with hard-to-treat gMG
Decision is first in world to favor zilucoplan, available under brand name Zilbrysq
UCB’s zilucoplan and Rystiggo (rozanolixizumab) both were approved in Japan to treat adults with generalized myasthenia gravis (gMG) who lack an adequate response to steroids or other immunosuppressive treatments.
“With the approval in Japan of zilucoplan and [Rystiggo], we are very proud and excited to expand our support to the gMG community and to offer new and additional choices allowing treatment to be tailored according to patient needs,” Iris Loew-Friedrich, MD, PhD, the executive vice-president and chief medical officer at UCB, said in a company press release.
This marks the first approval of zilucoplan, to be sold under the brand name Zilbrysq, anywhere in the world. The approval also makes Zilbrysq the first once-daily, under-the-skin MG therapy blocking C5, a protein whose activation contributes to the autoimmune attack behind MG.
Zilbrysq also is reported to be the only gMG-targeted therapy that can be self-administered by adult patients who are positive for self-reactive antibodies targeting the acetylcholine receptor (AChR), the most common type of MG-causing antibody.
Zilucoplan under review for approval in US, European Union
Regulatory authorities in the U.S. and European Union (EU) are considering zilucoplan’s approval for adults with AChR-related gMG. In the EU, the therapy received a positive recommendation for approval by a regulatory committee, and a decision by the European Commission is expected before year’s end.
The approval of Rystiggo — a once-weekly, under-the-skin therapy with a distinct mechanism of action relative to Zilbrysq — marks its second worldwide approval.
It follows a recent similar decision in the U.S. that covers gMG adult patients with antibodies against AChR or the muscle-specific tyrosine kinase (MuSK), the second most common target of MG-driving antibodies. Rystiggo also is being considered for approval in the EU, where a decision is anticipated next year.
“By providing these two medicines, each with their own mechanism of action, and way of administration, we are excited to support patients and physicians as they strive to manage the symptoms of gMG and to improve quality of life,” said Kanako Kikuchi, head of neurology and country operations at UCB Japan.
MG is caused by abnormal immune attacks that interfer with the molecular signaling between muscle and nerve cells, ultimately resulting in muscle weakness and other disease symptoms.
Different mechanisms of action, types of administration, mark 2 therapies
Zilbrysq and Rystiggo both are designed to dampen the MG-driving autoimmune attack, though through different mechanisms.
The first works by suppressing the C5 protein of the immune complement system, whose activation helps drive MG and other autoimmune diseases. In turn, Rystiggo ultimately speeds the breakdown of antibodies, including those causing MG, in the bloodstream.
Zilbrysq is administered once daily via under-the-skin, or subcutaneous, injection, which patients can perform at home with proper training. Rystiggo is given via a subcutaneous infusion pump once weekly for six weeks, with additional six-week treatment cycles administered based on a patient’s response.
Zilbrysq’s approval was supported mainly by data from a Phase 3 clinical trial called RAISE (NCT04115293), which tested the therapy against a placebo in 174 adults with gMG who were positive for anti-AChR antibodies.
Results showed that Zilbrysq significantly outperformed the placebo at easing MG symptoms and improving quality of life, with similar results across all subgroups of patients. Common side effects included bruising at the injection site, headache, diarrhea, and MG worsening.
Regulatory approvals of Rystiggo were based on data from the Phase 3 MycarinG trial (NCT03971422), in which 200 gMG adult patients with antibodies against AChR or MuSK received either Rystiggo or a placebo.
Data from MycarinG showed Rystiggo was significantly superior to a placebo at easing MG symptoms and these benefits were seen regardless of disease duration, prior treatments, and initial disease severity. Common side effects seen in the study were headache, infections, diarrhea, fever, allergic reactions, and nausea.