Therapeutic: telitacicept for autoimmune diseases

Published: 4-Jun-2024

Primary Sjögren syndrome (PSS) is a common autoimmune disease. It mainly affects the lacrimal and salivary glands, leading patients to experience dry eyes and mouth, but it can also affect other organs including the kidneys, lungs and nervous system

There is no specific therapy that restores gland secretion, with treatment restricted to symptom management such as the use of artificial tears.

Telitacicept is a novel fusion protein being developed by China’s RemeGen as a potential treatment for several autoimmune diseases, including PSS.1

It includes the extracellular domain of TACI, the human transmembrane activator, calcium modulator and cyclophilin ligand interactor, and the Fc domain of human immunoglobulin G.

It targets B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), two cell signalling molecules that are vital for B-lymphocyte development.

Inhibiting them reduces B-cell mediated autoimmune responses. A randomised, double-blind, placebo-controlled Phase II trial has been done in 42 patients with PSS.2

Subjects were given weekly subcutaneous doses of either 160 or 240 mg of telitacicept or a placebo for 24 weeks.

The lower dose gave a significant reduction in the EULAR PSS disease activity index from baseline to week 24, with a placebo adjusted 4.5% mean reduction.

For the higher dose, the decline was 2.7% with no statistical difference compared with the placebo. No serious adverse events were seen in the treatment group.

It is also being investigated in other autoimmune diseases, including systemic lupus erythematosus with rheumatoid arthritis, IgA nephritis and myasthenia gravis. For example, a randomised, open-label Phase II study was done in patients with generalised myasthenia gravis.3

In all, 29 patients who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies, and who were receiving standard of care therapy, were given weekly subcutaneous doses of 160 or 240 mg of the drug for 24 weeks on top of their standard of care treatment.

After 24 weeks, the mean reduction in quantitative myasthenia gravis score from baseline was 7.7 in the lower dose group and 9.6 for the higher group; the reductions after 12 weeks were 5.8 and 9.5, respectively.

There were no adverse events leading to discontinuation or death.

A Phase III trial is planned. In a Phase IIb trial in active systemic lupus erythematosus, 249 patients were randomised to receive 80, 160 or 240 mg weekly subcutaneous doses of telitacicept or a placebo once a week on top of standard therapy.4

At week 48, 76% of patients given the highest dose achieved an SLE Responder Index 4 response, with 68% in the 160 mg group, 71% with 80 mg and 34% with the placebo.

It was well tolerated, with adverse event profiles being similar across all treatment groups. Further trials are planned.


  1. F. Shi, et al., Immunopharmacol. Immunotoxicol. 43, 666 (2021).
  2. D. Xu, et al., Rheumatology (Oxford) 63, 698 (2024).
  3. J. Yin, et al., Eur. J. Neurol. 10, e16322 (2024).
  4. D. Wu, et al., Ann. Rheum. Dis. 83, 475 (2024).

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