Telitacicept for myasthenia gravis

Last updated Sep. 17, 2024, by Andrea Lobo, PhD
Fact-checked by Joana Carvalho, PhD

What is telitacicept for myasthenia gravis?

Telitacicept, formerly known as RC18, is a B-cell-targeting therapy being developed by Remegen as a potential treatment for myasthenia gravis (MG). Administered via under-the-skin (subcutaneous) injections, telitacicept is designed to reduce the activity of immune B-cells that drive MG.

Now in Phase 3 clinical testing, telitacicept has received orphan drug and fast track designations from the U.S. Food and Drug Administration (FDA) for MG. Both designations are intended to support and accelerate a therapy’s development.

In China, the therapy has been conditionally approved since 2021 for systemic lupus erythematosus, the most common form of lupus. It now is in clinical testing for several autoimmune conditions, including Sjögren’s disease, neuromyelitis optica spectrum disorder, and IgA nephropathy, a kidney disorder.

Therapy snapshot

How does telitacicept work in myasthenia gravis?

MG is a neuromuscular disease usually caused by self-reactive antibodies that interfere with nerve-muscle communication, leading to symptoms of muscle weakness and fatigue. Self-reactive antibodies are produced by a type of immune cells called B-cells, and they most commonly target acetylcholine receptors (AChRs) — proteins found on the surface of muscle cells that play a role in muscle contraction.

Telitacicept works to reduce the activity of B-cells. It specifically does so by blocking two proteins involved in B-cell development and maturation: B-cell lymphocyte stimulator, or BLyS, and A proliferation inducing ligand, known as APRIL.

The therapy is a recombinant or man-made fusion protein that combines an antibody protein fragment with a part of the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) receptor, a BLyS/APRIL receptor. Being equipped with a portion of the TACI receptor, telitacicept can bind to BLyS and APRIL, effectively preventing both proteins from interacting with receptors on B-cells and neutralizing their effects. This is expected to reduce the production of self-reactive antibodies  and ease MG symptoms.

How will telitacicept be administered in myasthenia gravis?

In clinical trials involving people with MG, telitacicept has been given as a weekly subcutaneous injection at various doses.

Telitacicept in myasthenia gravis clinical trials

Telitacicept’s safety and efficacy were evaluated in an open-label Phase 2 study (NCT04302103) that enrolled 29 adults with generalized MG, known as gMG. All of the patients were positive for anti-AChR antibodies and on standard therapy. Each was randomly assigned to receive either a low (160 mg) or a high dose (240 mg) dose of telitacicept, given by weekly subcutaneous injections, for 24 weeks, or about six months, in addition to standard of care.

The trial met its primary goal of reducing disease severity, as shown by a decrease in the Quantitative MG (QMG) score over the course of six months. The QMG scale is a clinician-rated measure of MG severity, in which higher values indicate more severe disease and disability.

After 12 weeks, or about three months, the QMG score decreased by a mean of 5.8 points in the low-dose group and by 9.5 points in the high-dose group. After 24 weeks, mean reductions had reached 7.7 points in the low-dose group and 9.6 points in the high-dose group.

Similar improvements were observed using the MG clinical absolute score scale, a measure widely used in China to assess different MG symptoms. In that assessment, higher scores also indicate more severe disease.

Despite the dose-dependent effects, by week 24, a similar proportion of patients in both groups achieved a QMG response (92.9% in the low-dose group and 100% in the high-dose group), meaning a score reduction of at least three points.

Moreover, both patient groups saw a significant reduction in the levels of different types of antibodies, including immunoglobulin G (IgG), IgA, and IgM, in the bloodstream.

Telacicept demonstrated a good safety profile, with no reported adverse events leading to treatment discontinuation or death, per the data. Most adverse events were considered mild to moderate in severity. All patients in the high-dose group experienced adverse events, compared with 78.6% of those in the low-dose group.

Ongoing trials

Telitacicept is now being tested in two Phase 3 clinical trials, recruiting patients in the U.S. or China.

The recently launched RemeMG trial (NCT06456580) will evaluate the therapy’s safety and efficacy in about 180 adults with gMG at three sites in Florida. It will involve patients positive for self-reactive antibodies targeting AChR or muscle-specific kinase (MuSK), another protein involved in nerve-muscle communication.

The participants will be randomly assigned to receive either telitacicept or a placebo, both given as subcutaneous injections, for 24 weeks. The trial’s primary goal is to assess if telitacicept can ease symptoms and improve the ability of patients to engage in daily activities compared with the placebo. This will be determined by evaluating changes in the scores of the MG Activities of Daily Living (MG-ADL) scale from the study’s start to week 24.

The researchers also will test whether the therapy can ease disease severity, by using the QMG scale, and if it is able to improve patients’ quality of life, after 24 weeks. The trial is expected to be completed in 2027.

The other trial (NCT05737160) testing telitacicept is underway across multiple locations in China. It is expected to enroll 100 adults with gMG who are positive for self-reactive antibodies targeting AChR or MuSK.

Participants will be randomly assigned to receive 240 mg of telitacicept, or a placebo, via weekly subcutaneous injections for 24 weeks. After that, patients will enter an open-label part of the trial, where they all will be treated with telitacicept for another 24 weeks. Its goals are similar to those of the RemeMG trial, but in this study, participants will be assessed for up to 48 weeks, or nearly a year. This study also is expected to be completed in 2027.

Common side effects of telitacicept

The most common side effects of telitacicept reported during clinical testing in gMG patients included:

• upper respiratory tract infections
• diarrhea
• injection site reactions.

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