UCB’s Rozanolixizumab and Zilucoplan Phase 3 Generalized Myasthenia Gravis studies published in prestigious The Lancet Neurology Journal
pharmafile | April 13, 2023 | News story | Business Services |
Brussels (Belgium) 13 April 2023 – 07:00 AM (CET) – UCB, a global biopharmaceutical company, today announced that The Lancet Neurology has published data from the phase 3 MycarinG study evaluating the efficacy and safety of rozanolixizumab in adult patients with acetylcholine receptor autoantibody-positive (AChR-Ab+) or muscle-specific tyrosine kinase autoantibody-positive (MuSK-Ab+) generalized myasthenia gravis (gMG) and the phase 3 RAISE study evaluating the efficacy and safety of zilucoplan in adult patients with mild to severe AChR-Ab+ gMG.[1],[2]
UCB is investigating both therapies as part of a broad offering to treat adult patients living with gMG throughout their treatment journey; each has an individual mechanism of action targeting the underlying disease pathology that causes gMG.
The safety and efficacy of rozanolixizumab and zilucoplan have not been established and neither treatment is approved for use in any indication by any regulatory authority worldwide.
“There is an ongoing need for well-tolerated, targeted treatment options to improve the quality of life of people living with gMG. Many of the current treatment options only offer symptomatic relief which results in a treatment burden in addition to the already substantial disease burden“ said Iris Loew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB. “These papers published in the Lancet Neurology further reinforce the potential of rozanolixizumab and zilucoplan – with their different MOAs – to provide targeted treatment options to patients to help them manage fluctuating and unpredictable symptoms both at home and in a healthcare setting.”
- In the MycarinG study1 (n=200) – the largest gMG population phase 3 study published to date – in adult patients with AChR-Ab+ or MuSK-Ab+ gMG, rozanolixizumab demonstrated statistically significant and clinically meaningful improvements in MG-specific outcomes in patients with MuSK-Ab+ or AChR-Ab+ gMG, that were consistent with prior published results. In the MuSK-Ab+ specific subgroup, improvement in MG-ADL was –7.28 (7mg/kg; n=5), –4.16 (10mg/kg; n=8), and 2.28 (placebo; n=8). In the AChR-Ab+ specific subgroup, improvement in MG-ADL was –3.03 (7mg/kg; n=60), –3.36, (10mg/kg; n=60), and –1.10 (placebo; n=59).
Both rozanolixizumab doses were generally well tolerated with similar occurrences of TEAEs between both doses. The most frequently reported TEAEs were headache, diarrhea, and pyrexia. A higher incidence of headache was reported in the rozanolixizumab groups versus placebo, with most cases mild to moderate and severe cases generally managed with non-opioid analgesics. Treatment discontinuation rates due to TEAEs were low.
Importantly, the MycarinG study included Patient-Reported Outcomes (PROs) measures also as a secondary endpoint of this study. The novel Myasthenia Gravis Symptoms PRO (MGS-PRO) – a measure used to assess symptom severity and impact of MG on patient lives, including physical fatigue which is not covered in other MG clinical outcome assessments – demonstrated statistically significant results vs placebo.
- In the RAISE study2 (n=174), in adult patients with mild to severe AChR-Ab+ gMG, zilucoplan demonstrated rapid efficacy, with consistent, sustained, clinically meaningful and statistically significant improvements versus placebo from baseline to week 12 in both patient and clinician-reported endpoints, including MG-ADL, which was the primary efficacy endpoint and, QMG and MGC and MGQoL15, which were secondary efficacy endpoints (the threshold for clinically meaningful MG-QoL15r has not yet been established).2
Zilucoplan was generally well-tolerated with a favorable safety profile. The most frequently reported TEAEs in the zilucoplan group were injection site bruising, headache, diarrhea, and (worsening of) MG.2 Incidences of serious TEAEs and serious infections were similar in both groups. All patients who completed the 12-week treatment period (n=166) chose to enroll in RAISE-XT, the ongoing open label extension study.2 As the first c5 complement inhibitor in gMG that patients can self-administer at home, the benefits of zilucoplan include reduced travelling time to and from hospitals, reduced interference with work obligations, and greater independence.2
“Our ultimate goal is to provide targeted treatment options that can help reduce the ongoing daily burden of gMG, giving patients flexible treatment options that work alongside their daily life,” said Charl van Zyl, Executive Vice President Neurology Solutions & Head of EU/International Markets, UCB. “With measures such as MGS-PRO in the MycarinG study, we have been able to see the positive impact rozanolixizumab has had on patient experience, while results from the RAISE study demonstrated the potential of zilucoplan as an effective and generally well-tolerated treatment that can be self-administered at home, giving people greater independence. These results bring us one step forward to being able to offer patients tailored options to meet their individual needs and preferences.”
Earlier this year, the US Food and Drug Administration (FDA) accepted UCB’s filing to review a Biologic License Application (BLA) for rozanolixizumab for the treatment of gMG in adult patients. The BLA was designated for Priority Review, with a response from the agency anticipated in Q2 2023. This BLA followed the European Medicines Agency’s (EMA) validation of the Marketing Authorization Application (MAA) for rozanolixizumab, and the FDA’s acceptance of a New Drug Application (NDA) and the EMA’s validation of the MAA for zilucoplan in the same indication. Regulatory applications for rozanolixizumab and zilucoplan for the treatment of gMG have also been filed in Japan. Responses from regulatory agencies to these submissions are expected in H2 2023.
gMG is a rare, chronic, heterogeneous (phenotypic and pathogenic), and unpredictable auto-immune disease characterized by dysfunction and damage at the NMJ.[3] Several factors are understood to be drivers of gMG disease pathology, including complement, immune cells and pathogenic IgG autoantibodies.[4]
People living with gMG can experience a variety of symptoms, including drooping eyelids, double vision, and difficulty in swallowing, chewing and talking, as well as severe muscle weakness that can result in life-threatening weakness of the muscles of respiration.[5],[6] MG is a rare disease with a global prevalence of 100–350 cases per every 1 million people.[7]
