Zilucoplan, now Zilbrysq, approved by FDA for AChR-positive gMG
UCB injection therapy is 1st in US that's once daily and self-given
The U.S. Food and Drug Administration (FDA) has approved zilucoplan, a once-daily injection therapy to now be marketed under the brand name Zilbrysq, for adults with generalized myasthenia gravis (gMG) who are positive for antibodies targeting the acetylcholine receptor (AChR).
With this approval, Zilbrysq has now become the first once-daily, complement-targeted, under-the-skin or subcutaneous injection therapy available for gMG in the U.S. It’s also the only gMG-targeted therapy that can be self-administered by patients.
“This is an important development for the community because, with more FDA-approved treatments for generalized myasthenia gravis, physicians have additional tools to treat this disease in individualized ways that are the right fit for each individual patient,” Samantha Masterson, president and CEO of the Myasthenia Gravis Foundation of America (MGFA), said in a press release.
The announcement from Zilbrysq’s developer, UCB, comes just a few weeks after the therapy received a similar approval in Japan. In both markets, the therapy previously known as zilucoplan will be sold under its new brand name Zilbrysq.
“With the FDA approval for Zilbrysq, we are very proud and excited to expand our support to the gMG community,” said Jean-Christophe Tellier, CEO of UCB, noting the company’s “tailored patient support services and commitment to widespread access.”
UCB says Zilbrysq approval will offer options to gMG patients
In September, the therapy also was recommended for approval in the European Union. There, a final decision is expected before year’s end.
The approval in the U.S. was welcomed by the community, and by the MGFA, a leading patient advocacy group.
“We are so grateful to UCB for being part of the myasthenia gravis community and their continued commitment to finding solutions for people living with this chronic, autoimmune, neuromuscular disease,” Masterson said.
In MG, the immune system produces self-reactive antibodies that disrupt the communication between nerves and muscles. Antibodies that target the AChR protein are the most common drivers of MG.
When one of these antibodies binds to AChR, it can trigger the activation of a group of immune proteins that are part of the complement system. These proteins normally become activated to fight off bacteria and other infectious agents, but in MG their activation contributes to the damaging immune response that characterizes the disease.
Zilbrysq works by blocking the activation of the complement cascade. It does so by specifically targeting a complement protein called C5. Other approved treatments for AChR-positive gMG, including Soliris (eculizumab) and Ultomiris (ravulizumab-cwvz), also work by targeting the C5 protein.
A key difference between Zilbrysq and these therapies is that both Soliris and Ultomiris are administered by an infusion directly into the bloodstream (intravenously), which needs to be done under the guidance of a healthcare professional. Zilbrysq instead is given by subcutaneous injection once daily.
After proper training, Zilbrysq injections can be given by caregivers or self-administered by patients — which UCB noted may be more convenient than regular intravenous infusions.
“Until now, people living with gMG have only had access to C5 therapy intravenously, which can be inconvenient and time consuming,” said Iris Loew-Friedrich, UCB’s executive vice-president and chief medical officer.
“Now, with the option of Zilbrysq, a self-administered once-daily, subcutaneous targeted complement C5 inhibitor, we hope a broad population of mild-to-severe adult patients with AChR-antibody-positive gMG will be able to have greater independence,” Loew-Friedrich said.
Approval of Zilbrysq supported by RAISE trial data
Zilbrysq’s approval was supported by data from a Phase 3 clinical trial called RAISE (NCT04115293). The study enrolled 174 adults with gMG who were positive for anti-AChR antibodies. Participants were randomly assigned to receive daily subcutaneous injections of either Zilbrysq (0.3 mg/kg) or a placebo for 12 weeks, or about three months.
The study’s main goal was to assess the effect of treatment on MG symptom severity and on how much these symptoms interfered with patients’ day-to-day lives, as measured by the MG Activities of Daily Living (MG-ADL) scale.
The results showed that patients on Zilbrysq experienced significantly greater MG-ADL score improvements compared with those on the placebo. MG-ADL scores measured from the trial’s start to week 12 were 2.09 points lower in Zilbrysq-treated patients than in those given the placebo.
The therapy also outperformed the placebo on measures of quality of life, as well as on other measures of MG severity. Recent analyses from the trial also have shown that Zilbrysq’s efficacy was similar across various subgroups of patients included in the trial.
“Zilbrysq demonstrated rapid improvements in gMG symptoms at week 12, with differences seen as early as one week, and provides a new treatment option for a broad population of AChR antibody-positive gMG patients,” said James F. Howard, MD, lead investigator of the RAISE trial at the University of North Carolina at Chapel Hill School of Medicine, adding that “Zilbrysq is designed for continued daily use.”
The most common side effects associated with Zilbrysq included diarrhea, upper respiratory infections, and injection site reactions. The therapy’s label carries a boxed warning noting that it may cause meningococcal infections, a potentially life-threatening type of bacterial infection. Due to this risk, Zilbrysq will only be available in the U.S. through a restricted risk evaluation and mitigation strategy (REMS) program called Zilbrysq REMS.
I am confident that UCB is the only company with a portfolio of two targeted therapies with different mechanisms of action and the experience to deliver truly individualized transformational patient value to people living with this often debilitating rare disease.
“We would like to extend our thanks to the patients, care partners, and investigators who participated in the RAISE study, and to our employees and collaborators, whose dedication and commitment to the gMG community made [Zilbrysq’s FDA approval] possible,” Tellier said.
Zilbrysq is the second therapy from UCB to be approved for MG this year. In late June, the FDA authorized UCB’s Rystiggo (rozanolixizumab-noli) to treat adults with gMG who are positive for anti-AChR antibodies, or for the second-most common type of MG self-reactive antibodies that target a protein called muscle-specific tyrosine kinase (MuSK).
“I am confident that UCB is the only company with a portfolio of two targeted therapies with different mechanisms of action and the experience to deliver truly individualized transformational patient value to people living with this often debilitating rare disease,” Tellier said.
Added Loew-Friedrich, “Our unique portfolio will support patients and healthcare professionals to tailor choice of treatment according to their individual needs.”