Telitacicept eases symptoms in treatment-resistant gMG: Study
Treatment reduces severity in patients with anti-AChR antibodies
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- Telitacicept reduces symptoms in anti-AChR antibody positive gMG.
- It benefits treatment-resistant and thymoma-associated gMG.
- The B-cell targeting therapy is approved in China for gMG.
Telitacicept safely and effectively reduces disease severity in people with generalized myasthenia gravis (MG) associated with anti-AChR antibodies, including when the disease is hard to treat or associated with a thymus tumor, a small study in China showed.
“Clinical outcomes showed increased efficacy of telitacicept when used earlier in the disease course, which leads to a sparing of prednisone,” the researchers wrote. Prednisone is a corticosteroid, a type of anti-inflammatory medication commonly used in gMG. Its long-term use is associated with serious side effects.
Telitacicept is approved in China as an add-on treatment for adults with gMG who are positive for antibodies targeting the AChR protein, the most common type of self-reactive antibody driving gMG. The therapy is being tested in a global Phase 3 clinical trial (NCT06456580), data from which may support future submissions for approval in the U.S. and other regions.
The study, “Telitacicept as a New Therapeutic Avenue for Generalized Myasthenia Gravis and Thymoma-Associated Myasthenia Gravis,” was published in the Journal of Neuroimmune Pharmacology.
Immune system attack
In gMG, the immune system mistakenly attacks proteins involved in nerve-muscle communication, leading to the hallmark MG symptoms of widespread muscle weakness and fatigue. These autoimmune attacks are driven by self-reactive antibodies produced by B cells.
Abnormalities in the thymus gland, an organ of the immune system where B-cells mature and are stored, are also present in most MG patients. About 10%-15% have tumors in the thymus, called thymomas.
“Thymoma-associated myasthenia gravis (TAMG) manifests severe and disease-resistant more frequently with the urgency of effective treatment,” the researchers wrote.
Telitacicept, developed by Remegen, is designed to reduce B-cell activity by targeting two proteins involved in their development and maturation: BLyS and APRIL. This is expected to help reduce the levels of self-reactive antibodies and ease symptoms of gMG.
Data from a completed China-based Phase 3 clinical trial (NCT05737160) showed that the therapy was superior to a placebo at reducing gMG severity and its impact on daily life after six months, with further improvements seen over nearly one year.
Retrospective analysis
A team of researchers in China evaluated the safety and efficacy of telitacicept in managing gMG associated with anti-AchR antibodies, particularly in treatment-resistant and thymoma-associated disease.
They retrospectively analyzed data from 22 gMG patients (68% women, mean age 53) who were treated with telitacicept for at least six months at a single Chinese hospital. All tested positive for anti-AchR antibodies, and most (68%) had late-onset MG (at age 50 or older). Nearly one-third (32%) had treatment-resistant disease, and 55% had thymomas.
Before starting telitacicept, all patients had received corticosteroids and pyridostigmine, an approved gMG therapy sold as Mestinon, with generics available. Half of the participants underwent thymectomy, or surgery to remove the thymus gland. Patients were followed for an average of 9.5 months after starting the treatment.
One month after telitacicept initiation, all participants experienced a clinically meaningful reduction in disease severity, defined as a drop of at least 3 points on the Quantitative MG (QMG) scale.
After three months, the mean QMG score decreased from 15.68 to 5.59, indicating a transition from moderate to mild disease. QMG scores continued to decline until the end of the study, reaching a mean of 1.72, “suggesting a continuous clinical improvement in telitacicept-treated patients,” the researchers wrote.
These positive effects were observed among patients with treatment-resistant disease and those with thymoma, suggesting that telitacicept had benefits across different subtypes of AChR-positive gMG.
Treatment was also associated with a significant reduction in scores on the MG Activities of Daily Living, which assesses the disease’s impact on daily activities, from a mean of 11.95 to 3.9 after three months, and a median of 1 at the end of the study.
Participants’ quality of life also improved, as reflected by a score reduction in the MG Quality of Life 15-item Scale from a mean of 22.23 to 11.27 after three months, and a median of 4 at the study’s end.
Overall, all but two participants achieved minimal symptom expression, meaning few or no symptoms, after about four months. The prednisone dose decreased from 27.72 mg/day to 6.14 mg after six months of treatment, and was below 5 mg at the end of the study for all patients.
After six months, there was also a significant reduction in the proportion of B-cells and levels of anti-AchR antibodies, “consistent with the mechanism of telitacicept for depleting [B-cells],” the researchers wrote.
Two patients experienced disease exacerbations, or sudden symptom worsening, both caused by upper respiratory tract infection. One required intravenous immunoglobulin and the other an increase in corticosteroid dosage, with both subsequently achieving minimal symptom expression.
Telitacicept was generally well tolerated, with the most common adverse events being redness and swelling at the injection site (18%) and upper respiratory tract infections (14%).
“Our study provides evidence to support that telitacicept is beneficial and well tolerated in the management of gMG, especially in refractory MG and TAMG,” the researchers wrote.
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