On 10 May, UCB announced more detailed results from two Phase III clinical trials in its generalised myasthaenia gravis (gMG) programme, firstly for zilucoplan, a complement C5 inhibitor, and secondly for rozanolixizumab, a neonatal Fc receptor (FcRn) antagonist. Based on these results, UCB is planning to file regulatory submissions for both drugs later this year. If approved, GlobalData expects these new products will help establish UCB as a new key player in the MG market.
Having announced top-line results in February this year, UCB’s double-blind, randomised, placebo-controlled RAISE study (NCT04115293) demonstrated that zilucoplan was significantly effective at improving gMG-specific outcomes in patients with acetylcholine receptor autoantibody-positive (AChR+) gMG compared with placebo. The trial met its primary endpoint of improvement in the Myasthaenia Gravis Activities of Daily Living (MG-ADL) score at week 12 with a placebo-corrected mean improvement of 2.12 points (p<0.001). In addition, zilucoplan demonstrated statistically significant improvements in secondary efficacy endpoints, including the Quantitative Myasthenia Gravis (QMG) score and Myasthaenia Gravis Quality of Life 15-Item revised (MG-QoL15r) score, as well as being well-tolerated.
If approved, zilucoplan would be the third complement C5 inhibitor approved for the treatment of MG and so will face significant competition from AstraZeneca’s Soliris (eculizumab), the current market leader, and Ultomiris (ravulizumab-cwvz), which was only approved by the US Food and Drug Administration (FDA) for MG last month. To be competitive, UCB is looking to differentiate zilucoplan through its route of administration: both Soliris and Ultomiris are administered via intravenous infusion by a healthcare professional, whereas zilucoplan can be self-administered as a subcutaneous injection.
But although self-administration can be more convenient for patients than regular infusion centre visits, zilucoplan requires daily administration, whereas Soliris requires administration once every two weeks and Ultomiris only once every eight weeks. The long-acting nature and convenient administration schedule of Ultomiris are expected to make it a game-changer for MG patients.
An important factor in zilucoplan’s uptake could be its cost of therapy. Key opinion leaders (KOLs) previously interviewed by GlobalData speculated that zilucoplan could be differentiated by lower pricing compared with the monoclonal antibodies (mAbs). But if priced at a similar annual cost of therapy to Apellis Pharmaceuticals’s Empaveli (pegcetacoplan), a synthetic peptide complement C3 inhibitor approved last year for paroxysmal nocturnal haemoglobinuria (the first approved indication for Soliris), the difference may only be by 10–15%.
UCB has also announced further results from its double-blind, randomised, placebo-controlled MycarinG study (NCT03971422) of rozanolixizumab in patients with AChR+ gMG, having previously announced the topline positive result in December last year. Rozanolixizumab significantly reduced MG-ADL scores from baseline, with a placebo-corrected mean improvement of 2.59 points at the 7mg/kg dose and 2.62 points at the 10mg/kg dose (p<0.001).
In addition, UCB has provided data on the MG Symptoms patient-reported outcomes (PRO) measure that it developed. This assesses quality-of-life outcomes such as physical fatigue and muscle weakness, which are important to patients and their ability to carry out daily activities. All the MG Symptoms PRO scales showed significant improvement from baseline with both rozanolixizumab doses compared with placebo. The trial also showed that rozanolixizumab was well-tolerated, with the majority of treatment-emergent adverse events being mild to moderate in intensity.
If approved, rozanolixizumab will face competition from Argenx’s Vyvgart (efgartigimod alfa), a mAb with the same FcRn-targeting mechanism of action, which was approved by the FDA for MG last year. Argenx is already looking to strengthen Vyvgart’s position in the market, with plans to file for a subcutaneous formulation later this year, complementing the already approved intravenous formulation and enabling greater penetration of the MG market. Competition within the anti-FcRn mAb class is set to further increase, with Johnson & Johnson’s nipocalimab currently in Phase III trials and HanAll Biopharma/ImmunoVent’s batoclimab expected to enter into Phase III pivotal trials in the near future.
The MG market is one of high potential for drug developers, as evidenced by the strong sales of Soliris for MG; GlobalData forecasts peak global (7MM: US, France, Germany, Italy, Spain, UK and Japan) sales of $1.4bn for Soliris in 2027 in this indication. In addition, there is high unmet need in the MG market, particularly for more effective therapies for refractory or difficult-to-treat disease, so this is becoming increasingly competitive, with more companies looking to become key players.
AstraZeneca recently became the market leader through its acquisition of Alexion Pharmaceuticals and associated products, Soliris and Ultomiris, which closed in July last year. But with the US patent expiry of Soliris expected in 2027, and the entry of new products into the MG market in the next couple of years, it is unlikely that AstraZeneca will remain the only major player in the market. UCB is well-positioned to become a new key player, with both zilucoplan and rozanolixizumab expected to enter the market next year.