Inebilizumab continues to lead to reductions in gMG severity in trial
Amgen's antibody-based therapy meets primary goal of ongoing Phase 3 trial
Two doses of inebilizumab, Amgen’s antibody-based therapy, led to sustained reductions in the severity of generalized myasthenia gravis (gMG) among patients for up to six months, meeting the primary goal of an ongoing Phase 3 clinical trial.
The trial, called MINT (NCT04524273), demonstrated that inebilizumab’s benefits extend to people with gMG who have self-reactive antibodies targeting either the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK), the two most common types of MG-causing antibodies.
Based on these data, Amgen now plans to seek the therapy’s approval in the U.S., followed by similar filings in other key markets, the company said in a press release.
“Patients living with generalized myasthenia gravis deserve an effective treatment option that provides long-term symptom relief,” said Jay Bradner, MD, executive vice president of research and development and chief scientific officer at Amgen. “Once approved, [inebilizumab] is expected to offer a new option for patients earlier in their treatment plan.”
gMG is an autoimmune disorder driven by self-reactive antibodies produced by a type of immune cells called B-cells. These self-reactive antibodies target proteins, mainly AChR or MuSK, that are involved in nerve-muscle communication, disrupting the process and leading to the disease’s hallmark symptoms of muscle weakness and fatigue.
“While there are treatments currently available for gMG, some patients continue to be inadequately managed and/or don’t tolerate other medications (due to [adverse events]), or have a high burden of treatment (due to frequent infusions/injections),” Richard J. Nowak, MD, the study’s global principal investigator and director of the Myasthenia Gravis Clinic at Yale University in Connecticut, said in an emailed statement to Myasthenia Gravis News.
Inebilizumab widely approved as Uplizna to treat NMOSD
Inebilizumab is designed to bind to a protein called CD19 that’s found on the surface of B-cells, triggering the death of multiple types of disease-driving B-cells, including immature and mature B-cells. By depleting or lowering the numbers of these B-cells, inebilizumab may reduce the production of self-reactive antibodies and, consequently, ease disease activity and gMG symptoms.
According to Bradner, inebilizumab “targets CD19-[positive] pre-B cells, mature B-cells and some plasmablasts, which are drivers of the disease.”
The therapy, under the brand name Uplizna, is already approved in several countries, including the U.S., Brazil, and Canada, and in the nations of the European Union, to treat neuromyelitis optica spectrum disorder, an autoimmune disease affecting the nervous system.
MINT is an ongoing clinical trial testing inebilizumab that enrolled 238 people with gMG. Among them, 190 had anti-AChR antibodies, and 48 had anti-MuSK antibodies.
The participants were randomly assigned to receive 300 mg of inebilizumab or a placebo, given by infusions directly into the bloodstream (intravenously) 15 days apart at the study’s start. An additional dose was given after six months in patients with anti-AChR antibodies.
After the placebo-controlled portion of the trial, which lasted six months for patients with anti-MuSK antibodies and one year for those with anti-AChR antibodies, all participants had the option to enroll in an open-label extension. In it, patients continue, or start, receiving inebilizumab.
For patients who entered the study taking corticosteroids, the dose of prednisone was tapered down to 5 mg daily, from week 4 to week 24.
“MINT is also the only Phase 3 biologic trial that included a protocol-specified steroid taper, an important consideration for patients as effects of prolonged high-dose steroid use contribute to the overall burden of disease,” Nowak stated in the release.
According to previously reported top-line data, MINT met its primary goal, with inebilizumab significantly reducing the scores of the MG Activities of Daily Living (MG-ADL) over the course of approximately six months compared with the placebo. MG-ADL is a patient-reported scale that assesses MG symptoms and their impact on daily activities, with lower scores indicating less impairment.
New MINT trial data presented at scientific meeting
Now, Amgen presented additional data from MINT at the American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting, taking place this month, in Savannah, Georgia.
In key secondary measures, inebilizumab significantly outperformed the placebo in its ability to reduce MG-ADL scores from the study’s start to week 26 in patients with anti-AChR antibodies (mean drop of 1.8 points) and in those with anti-MuSK antibodies (mean drop of 2.2 points).
Among anti-AChR-positive patients, inebilizumab also significantly lowered the scores of the Quantitative MG (QMG) scale, a physician-guided measure of disease severity, by 2.5 points compared with the placebo. While there was a trend toward improvement in patients with anti-MuSK antibodies, the difference relative to the placebo was not statistically significant.
“MINT findings provide … evidence for the safety and efficacy of [inebilizumab], a twice-yearly infused medicine, in adult gMG patients with either AChR[positive] and MuSK[positive] autoantibodies through week 26,” Nowak said in the email.
[Inebilizumab] represents a novel approach to the management of MG. … These results support the role of anti-CD19 B-cell depletion therapy for the treatment of MG.
The therapy’s overall safety profile during MINT was consistent with that already known. The most common treatment-emergent adverse events reported were COVID-19, cold-like symptoms, urinary tract infection, infusion-related reactions, headache, and cough.
Bradner said these MINT results, which he called “clinically significant,” provide “growing evidence for [inebilizumab’s use] in severe autoimmune diseases and reinforce Amgen’s leadership in B-cell targeting therapeutics.”
For his part, Nowak said inebilizumab “represents a novel approach to the management of MG.”
“[The therapy] targets the upstream immunopathogenic disease drivers,” Nowak said, adding that “these results support the role of anti-CD19 B-cell depletion therapy for the treatment of MG.”
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