Inebilizumab eases gMG symptoms in anti-AChR antibody patients
New MINT trial data show improved daily function over 1 year of treatment
One year of treatment with inebilizumab eased symptoms and improved daily functioning for people with generalized myasthenia gravis (gMG) positive for antibodies against the acetylcholine receptor (AChR), according to new data from the Phase 3 MINT clinical trial.
Amgen, the company developing inebilizumab, will present the new data next month at the annual meeting of the American Academy of Neurology (AAN) in San Diego. While still being developed for gMG, inebilizumab is already approved under the brand name Uplizna to treat neuromyelitis optica spectrum disorder, an antibody-driven autoimmune disease that affects the brain and spinal cord.
“I’m looking forward to further examining the 52-week MINT data with my colleagues in the neurology community at AAN. These results showed that Uplizna consistently relieved burdensome symptoms and improved activities of daily living for gMG patients,” Richard J. Nowak, MD, global principal study investigator for the MINT trial and director of the Myasthenia Gravis Clinic at Yale University, said in a press release from Amgen.
Per the release, these new results show “durable and sustained efficacy” with the therapy when given in two doses per year, following an initial loading dose.
New data add to benefits seen in top-line results last year
Myasthenia gravis (MG) is an autoimmune disorder in which antibodies disrupt the communication between nerve and muscle cells, leading to symptoms of muscle weakness and fatigue. Antibodies targeting AChR are the most common cause of MG.
Inebilizumab is an antibody-based therapy designed to deplete or lower the number of B-cells, which are the immune cells responsible for producing antibodies. By doing so, inebilizumab is expected to lower the levels of MG-causing antibodies and thus help ease signs and symptoms of the disease.
The therapy is given intravenously, or by an infusion into the bloodstream. The first two infusions are administered two weeks apart, with subsequent ones given every six months.
The Phase 3 MINT clinical trial (NCT04524273) enrolled 238 adults with gMG, including 190 who were positive for anti-AChR antibodies. The other 48 participants had antibodies against muscle-specific kinase, or MuSK, the second-most common type of MG-causing antibodies.
Participants who were positive for anti-AChR antibodies were randomly assigned to receive inebilizumab or a placebo for 52 weeks, or one year; those positive for anti-MuSK antibodies were given inebilizumab or a placebo for 26 weeks, or six months. Patients who completed the placebo-controlled portion of the study had the option to enroll in an open-label extension in which all are treated with inebilizumab for up to three years.
The main goal of the MINT trial was to determine if inebilizumab was better than the placebo at reducing scores after 26 weeks on the MG Activities of Daily Living (MG-ADL). The MG-ADL is a patient-reported scale of MG severity that evaluates the disease’s impact on an individual’s day-to-day life, with higher scores indicating more severe disease and a greater impact.
Top-line results released last year showed that inebilizumab bested the placebo in its ability to improve MG-ADL scores after six months in all patients. Amgen previously announced plans to submit an application seeking the treatment’s regulatory approval for gMG based on those results.
Inebilizumab benefits over 70% of anti-AChR-positive patients
The new data cover the outcomes of anti-AChR-positive patients who were followed out to one year. After the year, MG-ADL scores in these patients were, on average, 2.8 points lower — a better score, as it indicates less disability — with inebilizumab compared with the placebo.
Nearly three-quarters (72.3%) of anti-AChR-positive patients given inebilizumab experienced an improvement in MG-ADL scores of at least three points. By contrast, fewer than half (45.2%) of those given the placebo experienced such an improvement.
It is encouraging to see that Uplizna demonstrated continued improvements in efficacy in patients with [AChR-positive] gMG through week 52. … These additional data from MINT further support the role of Uplizna … as a potential targeted treatment option for gMG.
Scores on the Quantitative MG (QMG) scale, a clinician-rated measure of MG symptom severity, also favored inebilizumab over the placebo after one year of treatment. Average QMG scores in these patients were more than four points better with inebilizumab than the placebo after one year.
More than two-thirds (69.2%) of anti-AChR-positive patients treated with inebilizumab saw their QMG scores improve by at least three points after one year — an outcome that was seen in less than half (41.8%) of those on the placebo.
“It is encouraging to see that Uplizna demonstrated continued improvements in efficacy in patients with [AChR-positive] gMG through week 52,” Nowak said in an emailed statement to Myasthenia Gravis News. “These additional data from MINT further support the role of Uplizna … as a potential targeted treatment option for gMG.”
Nowak added that “it is also important to note that this sustained efficacy was achieved in MINT with a protocol-specified steroid taper.” That means, according to the scientist, that all patients, starting at week 4, reduced their prednisone use — to 5 mg per day by week 24.
“This consideration is particularly important, as prolonged moderate-high dose steroid use can have harmful effects and significantly contribute to the overall burden of disease for … patients,” Nowak said.
Long-term safety data from the MINT study were consistent with the safety profile of inebilizumab seen in other diseases. The most common safety issues were infusion-related reactions, the common cold, and urinary tract infections, per the release.
Jay Bradner, MD, executive vice president of research and development at Amgen, said “the 52-week MINT trial results highlight the potential for a new standard of care in gMG.” Treatment with inebilizumab “[offers] durable symptom relief with a simplified treatment regimen,” Bradner said.
“These findings reinforce Uplinza’s ability to provide sustained symptom relief with just two doses per year — an important advancement for patients living with generalized myasthenia gravis — while underscoring our commitment to developing transformative therapies for people facing complex autoimmune diseases,” Bradner said.
About the Author
