Efficacy and safety of telitacicept in patients with SLE: Results from a phase III trial

Telitacicept, a recombinant fusion protein consisting of the extracellular domain of the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) receptor + the fragment crystallizable region (Fc) domain of human immunoglobulin G (IgG), is a novel therapeutic agent for systemic lupus erythematosus (SLE).¹ The extracellular domain of the TACI receptor binds and suppresses B-lymphocyte stimulator (BLyS) and proliferation-inducing ligand (APRIL) signaling, while the Fc domain of human IgG increases the stability of telitacicept.¹

Blocking BLyS can prevent the maturation of immature B cells and therefore prevent the recurrence of the disease.² Blocking APRIL can inhibit the differentiation of mature B cells into plasma cells and thereby prevent the release of autoantibodies by autoreactive plasma cells, which can effectively suppress immune responses and manage the autoimmune symptoms.²

At the European Alliance of Associations for Rheumatology (EULAR) 2023 Congress, Van Vollenhoven et al. presented phase III trial results on the efficacy and safety of telitacicept in patients with SLE.¹ Below, we summarize the key findings.

Methods¹

This was a double-blind, randomized, placebo-controlled phase III study assessing the efficacy and safety of telitacicept in patients with SLE. The study design is illustrated in Figure 1.

ACR, American College of Rheumatology; ANA, antinuclear antibody; Anti-dsDNA, anti-double-stranded deoxyribonucleic acid antibody; Ig, immunoglobulin; PGA, Physician’s Global Assessment; SC, subcutaneous; SELENA-SLEDAI, Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index; SLE, systemic lupus erythematosus; SRI, SLE responder index.
*Adapted from Van Vollenhoven et al.¹

Results¹

A total of 335 patients with SLE were included, of which 167 received telitacicept 160 mg and 168 received placebo. Both groups had comparable baseline demographics and disease characteristics. Mean age was ≈35 years and >90% patients were female (Table 1).

Table 1. Baseline demographics and disease characteristics*

ANA, antinuclear antibody; dsDNA, double-stranded DNA; BILAG, British Isles Lupus Assessment Group; BMI, body mass index; PGA, physician’s global assessment; SD, standard deviation; SLE, systemic lupus erythematosus; SELENA-SLEDAI, Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index. *Adapted from Van Vollenhoven, et al.1
Characteristics, % (unless otherwise stated)	Placebo (n = 168)	Telitacicept 160 mg (n = 167)
Female	93.5	91.0
Mean age (SD), years	35.1 (10.45)	34.8 (9.77)
Mean BMI (SD), kg/m2	22.67 (3.89)	23.01 (3.41)
Mean SLE disease duration (SD); years	7.21 (5.32)	7.54 (5.53)
Mean SELENA-SLEDAI score (SD)	11.5 (3.64)	11.5 (3.14)
At least BILAG 1A or 2B	59.5	62.9
Mean PGA (SD)	0.47	0.44
Serum biomarkers
Low C3 and/or C4	70.2	71.3
Positive ANA	98.2	95.8
Mean proteinuria (SD)	1.237 (1.343)	1.395 (1.571)
Glucocorticoid (prednisone equivalent) dose >7.5 mg/day	73.8	70.7
Monotherapy
Glucocorticoid	0	0.6
Antimalarials	1.8	0
Immunosuppressive                drugs	0.6	0.6
Combination therapy
Glucocorticoids +                antimalarials	15.5	15.0
Glucocorticoids +                immunosuppressives	14.3	13.8
Glucocorticoids +                immunosuppressives +             antimalarials	67.9	70.1

Efficacy¹

The study met its primary endpoint as a significantly greater proportion of patients receiving telitacicept achieved SRI-4 response at Week 52 compared with those receiving placebo (Figure 1). Additionally, SRI-4 response was sustained for up to Week 52 in the telitacicept group. Time to first SLE flare was significantly longer among patients receiving telitacicept compared with placebo (median 95% confidence interval [CI], 198 [169–254] days vs 115 [92–140] days, respectively; p < 0.001).

FAS, full analysis set; mITT; modified intention-to-treat; SRI, SLE responder index.
*Adapted from Van Vollenhoven et al.^1
†Missing data imputed as ‘non-response’.

The key secondary outcomes are depicted in Figure 2. A significantly greater proportion of patients treated with telitacicept showed improvement in SELENA-SLEDAI and PGA compared with those treated with placebo (p < 0.001).

PGA, physician’s global assessment; SELENA-SLEDAI, Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index.
*Data from Van Vollenhoven, et al.¹

Additionally, telitacicept treatment was associated with a rapid and sustained increase of complement levels (C3 and C4) and reduction of immunoglobulins (IgM, IgG, and IgA) and CD19⁺ B cells.

Safety and tolerability¹

Most treatment-emergent adverse events (TEAEs) were of mild to moderate severity (Table 2). TEAEs and infections were comparable between the treatment groups, while the incidence of serious AEs and serious infections was higher in the placebo versus telitacicept group. There were no deaths reported in either group.

Table 2. Safety and tolerability*

SAE, serious adverse event; SOC, system organ class; TEAE, treatment-emergent adverse event. *Adapted from Van Vollenhoven, et al.1 †Adverse events with an incidence of ≥3% within this SOC in any group.
Event, % (unless otherwise stated)	Placebo (n = 168)	Telitacicept (n = 167)
TEAEs	84.5	91.6
Drug-related TEAEs	50	74.9
TEAE leading to discontinuation	5.4	4.8
SAEs	2.4	1.2
Infections and infestations (SOC)†	60.1	65.3
Upper respiratory tract      infections	32.7	42.5
Urinary tract infection	15.5	11.4
Nasopharyngitis	6.5	2.4
Herpes zoster	3.6	4.8
Gastroenteritis	3.0	5.4
Serious infections	5.4	1.2
Severe infections	4.8	1.2
Psychiatric disorders	3.0	2.4

Conclusion¹

This phase III trial of telitacicept in patients with SLE met its primary efficacy endpoint. Treatment with telitacicept (160 mg weekly) demonstrated favorable clinical outcomes and an acceptable safety profile in patients with moderate to severe SLE.

Telitacicept obtained its first approval in China in 2021 for the treatment of patients with active SLE. Currently, a global phase III trial (REMESLE-1) is at the enrolment stage.