Zilucoplan Under Review in US and EU to Treat Generalized MG
Approval requests to FDA, EMA supported by Phase 3 RAISE trial results
The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have agreed to review applications seeking the approval of zilucoplan to treat generalized myasthenia gravis (gMG).
UCB, the therapy’s developer, announced the FDA accepted its new drug application (NDA), requesting zilucoplan be approved to treat adults with gMG who are positive for self-reactive antibodies targeting the acetylcholine receptor (AChR), the most common type of MG-causing antibody.
The company’s marketing authorization application (MAA) to the EMA, meanwhile, seeks zilucoplan’s approval for anti-AChR-positive gMG adults who require treatment in addition to steroids or non-steroidal immunosuppressants.
Zilucoplan seen to ease gMG symptoms, aid daily life in RAISE trial
“The acceptance of the NDA by the FDA as well as the acceptance of the MAA by the EMA, brings us one step further on our journey towards approval for this medicine,” Charl van Zyl, executive vice president of neurology solutions and head of EU/international markets at UCB, said in a company press release.
Similar requests for zilucoplan’s approval are planned for other countries, including Great Britain and Japan, UBC stated.
Both filings are supported by data from the Phase 3 RAISE trial (NCT04115293), which tested zilucoplan against a placebo in 174 adults with gMG who were positive for AChR antibodies. Participants self-administered either zilucoplan (0.3 mg/kg) or a placebo — via under-the-skin injections — once daily for about three months.
Top-line trial data, announced early this year, showed its main goal was met: scores on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale, a measure of MG’s severity and impact one daily life, on average favorably differed by slightly more than two points for zilucoplan-treated patients relative to those on placebo at the study’s end. Other measures of MG severity and life quality also favored zilucoplan over placebo.
“People who live with gMG suffer unpredictable, fluctuating, and debilitating symptoms, which have a huge impact on their lives. We want to help reduce the day-to-day burden of this challenging disease,” said Iris Loew-Friedrich, executive vice-president and chief medical officer at UCB.
“If approved, zilucoplan has the potential to address the unmet need for people with gMG by providing targeted improvements in signs and symptoms of gMG disease activity and severity,” Loew-Friedrich added.
No new major safety concerns were identified in RAISE, with the most common treatment-associated side effects being bruising at the injection site, headache, and diarrhea. Few study participants discontinued treatment due to side effects, UCB reported.
Zilucoplan is designed to block the activation of the complement cascade, a group of inflammatory proteins that play a role in the autoimmune attack that drives MG. The therapy, which has been designated an orphan drug by the FDA, specifically targets a complement protein called C5.
Plans are also in the works to request the approval of rozanolixizumab, another potential gMG therapy, by year’s end, UCB announced.
Results of the Phase 3 rozanolixizumab study, released in limited detail late last year, indicated infusions of the therapy eased symptoms and improved daily life for adult patients. Rozanolixizumab is designed to target the human neonatal Fc receptor (FcRn) protein to lower levels of immunoglobulin G (IgG) antibodies, which help to fight infection but can be self-reactive in this disease.
“A benefit of targeted treatment is that it may help reduce the adverse events that can be associated with non-specific immunosuppressive treatment of gMG,” Loew-Friedrich said.
All RAISE study patients who completed its 12 weeks chose to enroll in the open-label RAISE-XT (NCT04225871) extension trial, where they are being treated with zilucoplan and followed to assess its long-term safety and efficacy.