SAVANNAH, Ga. -- Inebilizumab (Uplizna) had clinically meaningful efficacy and a favorable safety profile among people with generalized myasthenia gravis (gMG), topline data from the MINT trial showed.
The anti-CD19 monoclonal antibody was effective in a combined population with acetylcholine receptor autoantibody-positive (AChR+) or muscle-specific kinase autoantibody-positive (MuSK+) gMG, said Richard Novak, MD, MS, of Yale University in New Haven, Connecticut.
The primary endpoint of the phase III study -- the change from baseline on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in the combined AChR+ and MuSK+ population -- favored the inebilizumab group with MG-ADL scores of -4.2 points at week 26, compared with -2.2 points for placebo (difference 1.9 points, P<0.0001), Novak reported at the Myasthenia Gravis Foundation of America (MGFA) session of the American Association of Neuromuscular and Electrodiagnostic Medicine annual meeting. The MG-ADL scale ranges from 0 to 24, with higher scores indicating more severe symptoms.
"Inebilizumab is a humanized monoclonal antibody that causes targeted and sustained depletion of CD19-positive B cells, including plasmablasts and some plasma cells, that are integral to the pathogenesis of generalized myasthenia gravis," Novak said.
The drug currently is approved to treat neuromyelitis optica spectrum disorder (NMOSD) patients who are positive for anti-aquaporin-4 antibodies.
Since 2017, five drugs have been approved to treat myasthenia gravis: eculizumab (Soliris), efgartigimod (Vyvgart), rozanolixizumab (Rystiggo), ravulizumab (Ultomiris), and zilucoplan (Zilbrysq).
MINT was a placebo-controlled study that randomized 238 participants with gMG, 190 who were AChR+ and 48 who were MuSK+. The double-blind period was 26 weeks for the MuSK+ population and 52 weeks for the AChR+ group.
Half of participants in each group were randomized to 300 mg inebilizumab and half to placebo, given on days 1 and 15 of the study. The AChR+ group had an additional dose after 6 months and follow-up at 1 year.
Eligible participants had a Myasthenia Gravis Foundation of America MGFA classification II, III, or IV disease; an MG-ADL score at screening and randomization between 6 and 10 with over 50% of this score attributed to nonocular items, or an MG-ADL score of 11 or higher; and a Quantitative Myasthenia Gravis (QMG) score of 11 at screening and randomization.
Mean baseline age was about 48 and more than half of the study sample was female. More than 90% had MGFA class II or III disease. Mean MG-ADL score was about 9, mean QMG score was about 17, and about 82% of participants used more than 5 mg prednisone (or its equivalent) at baseline.
Starting at the week 4 visit, participants who were on corticosteroids underwent a protocol-specified prednisone taper to 5 mg per day by week 24. The taper was an "important consideration for patients, as effects of prolonged high-dose steroid use contribute to the overall burden of disease," Novak noted.
At week 26, those treated with inebilizumab in the combined AChR+ and MuSK+ population had a 4.8-point reduction in QMG scores, compared with a 2.3-point reduction for those who received placebo (difference 2.5 points, P=0.0002). The QMG scale ranges from 0 to 39, with higher scores indicating more severe impairment.
MG-ADL score changes favoring inebilizumab over placebo were significant at week 26 in both the AChR+ and the MuSK+ populations, Novak said. QMG score changes at week 26 were statistically significant in the AChR+ group, but not in the MuSK+ group.
Reported treatment-emergent adverse events were similar in frequency between the inebilizumab and placebo groups at week 26. One participant in the inebilizumab group died of septic shock and pneumonitis, which may have been due to acute respiratory syndrome caused by myasthenic crisis. In the placebo group, two participants died; one by cardiorespiratory arrest which may have been related to myasthenic crisis, and one by respiratory distress due to disease progression.
No new safety signals were identified. The overall profile during the study period was consistent with the known safety profile for NMOSD, Novak said.
Analyses of additional endpoints including myasthenia gravis exacerbations, steroid tapering, quality of life, and durability of response are ongoing, he added. Efficacy data for AChR+ patients over 12 months will be presented at a later date. Based on the MINT primary results, drugmaker Amgen is planning to file for FDA approval.