Amgen's inebilizumab, already approved for neuromyelitis optica spectrum disorder (NMOSD), has demonstrated promising results in a Phase 3 trial (MINT) for generalized myasthenia gravis (gMG). The study, involving 238 patients, showed statistically significant improvements in MG-ADL scores compared to placebo, paving the way for potential regulatory submissions. This development addresses a significant unmet need for more durable and less frequent dosing options in gMG treatment.
Inebilizumab's Efficacy in MINT Trial
The MINT trial (NCT04524273) randomly assigned patients with gMG to either intravenous inebilizumab 300 mg or placebo for 12 months. The primary endpoint, change from baseline in MG-ADL scores, was significantly better in the inebilizumab group (-4.2) compared to the placebo group (-1.9, P < .0001). The study included both AChR-Ab+ and MuSK-Ab+ patients, representing the largest cohort of MuSK-Ab+ patients in a therapeutic trial to date. At week 26, inebilizumab also showed statistically significant improvement in Quantitative Myasthenia Gravis (QMG) scores compared to placebo (inebilizumab: -4.8; placebo: -2.5; P = .0002).
Novel Therapeutic Approaches in Development
Several other trials are exploring novel therapeutic approaches for gMG. The Phase 3 NIMBLE trial (NCT05070858) is evaluating the combination of pozelimab and cemdisiran, inhibitors of complement C5, in patients with gMG. The PREVAIL study (NCT05556096) is assessing gefurulimab, a bispecific nanoantibody that binds to C5, in AChR-Ab+ gMG patients. Additionally, the ADAPT SERON trial (NCT06298552) is investigating the efficacy of intravenous efgartigimod in seronegative gMG patients, a population often excluded from traditional trials.
Cladribine for Myasthenia Gravis
The Phase 3 MyClad study is assessing cladribine, a previously approved therapy for multiple sclerosis, in MG. The trial plans to recruit 240 participants, including AChR-positive, MuSK-positive, and seronegative patients. The primary endpoint is the change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score over a 24-week period.
Addressing Unmet Needs in gMG Treatment
Despite available treatments, significant unmet needs remain in gMG, including the need for more durable responses, less frequent dosing, and therapies that allow for steroid tapering. Current treatments, such as corticosteroids, can have harmful long-term effects. The development of new therapies like inebilizumab and the exploration of novel approaches in ongoing trials offer hope for improved outcomes and a better quality of life for patients with gMG.
