Telitacicept fusion protein is effective and safe in patients with rheumatoid arthritis who had inadequate response to methotrexate, phase 3 study shows
Presenter: Qing Zuraw, MD, MPH, MBA, Senior Vice President, Head of Global Autoimmune Disease Clinical Development, RemeGen Biosciences, Inc, San Francisco, CA.
Telitacicept, a Human Recombinant Fusion Protein Targeting and Neutralizing B Lymphocyte Stimulator (BlyS) and a Proliferation-Inducing Ligand (APRIL), in Rheumatoid Arthritis (RA) Patients with an Inadequate Response to Methotrexate (MTX): A Randomized, Double-Blind, Phase 3 Study. Abstract L20. Presented Nov 15, 2023.
Telitacicept, a fusion protein of two key cell-signaling molecules, is effective and safe in patients with rheumatoid arthritis (RA) that had inadequate response to methotrexate, according to results of a randomized, placebo-controlled trial presented at the ACR Convergence 2023.
Results showed that a significantly higher proportion of telitacicept-treated patients achieved an ACR20 response at week 24 as compared to placebo. Further, the safety and tolerability of telitacicept was similar to placebo, including a similar incidence rate for infections, said Qing Zuraw, MD, MPH, MBA, who reported the findings in a late-breaking abstract session. Dr Zuraw is the senior vice president and head of Global Autoimmune Disease Clinical Development with RemeGen Biosciences in San Francisco, CA.
Telitacicept, which targets and neutralizes B lymphocyte stimulator (BlyS) and a proliferation-inducing ligand (APRIL), was approved in China in March 2021 for the treatment of moderate to severe systemic lupus erythematosus. It is being developed by RemeGen for other diseases including RA, according to the company’s website.
In an interview with Cleveland Clinic Journal of Medicine, Dr Zuraw said the findings of the present phase 3 study in RA are promising, with a safety profile that does not suggest it is at risk of the black box safety warnings that accompany anti-tumor necrosis factor (TNF) agents or janus kinase (JAK) inhibitors. However, Dr Zuraw added, it is still too early to determine the potential role of telitacicept in the treat-to-target paradigm.
“Given its safety and efficacy profile, we envision that telitacicept has potential as a new RA therapy, and it may have a valuable place in the arsenal rheumatologists have in achieving remission in RA via the treat-to-target concept,” said Dr Zuraw.
Although the study did not include an active comparator arm, the clinical response by ACR20 and ACR50 in the phase 3 RA study of telitacicept was comparable to published data on other molecules such as the TNF inhibitors.
“More importantly, the trial demonstrated telitacicept’s ability to prevent structural damage as early as week 24, compared to anti-TNF at week 52,” said Dr Zuraw.
The present phase 3 randomized, double-blind placebo-controlled phase 3 study evaluated the efficacy and safety of telitacicept 160 mg in patients with moderate-to severe RA and an inadequate response to methotrexate.
A total of 360 patients were randomized to receive telitacicept and 119 patients to placebo in the study, which included a 24-week treatment period (results of which were reported at ACR Convergence 2023) and an open-label follow-up period of an additional 24 weeks. The primary endpoint for efficacy was the percentage of patients with ACR20 response by week 24.
The mean age of enrolled patients was 49.1 years in the telitacicept arm and 49.6 in the placebo arm. According to investigators, key demographics and disease characteristics were similar with the exception of C-reactive protein, which was higher in the telitacicept group, at 22.86 mg/L as compared to 17.29 mg/L in the placebo group.
The primary endpoint of the study was met, with 60.0% of patients in the telitacicept group achieving an ACR20 response by week 24 versus 26.9% in the placebo group (P < .001). Similarly, ACR50 response rates at week 24 were 21.4% for telitacicept versus 5.9% for placebo (P < .001).
In addition, the telitacicept group had a significantly greater reduction from baseline in the Disease Activity Score-28 (DAS28) than placebo, calculated using erythrocyte sedimentation rate (ESR), investigators reported. At week 24, the proportion of patients achieving a DAS28-ESR of 3.2 or lower was 14.7% for telitacicept and 5.0% for placebo (P < .05).
Other secondary endpoints demonstrated the efficacy of telitacicept as compared to placebo, according to investigators. They reported significantly greater proportions of patients with improvements in HAQ-DI, Patient’s Assessment of Pain, Patient’s Global Assessment of Disease Activity, Physician’s Global Assessment of Disease Activity, and reduction in ESR.
Radiographic endpoints also favored telitacicept over placebo, investigators said, with significantly less progression of joint damage, and a significantly higher proportion of patients with no radiographic progression at week 24.
Safety endpoints were comparable between groups, including similar incidence of serious adverse events, treatment-emergent adverse events (including those leading to treatment discontinuation), and serious infections, which occurred in 2.2% of the telitacicept group and 3.4% of the placebo group.
Further study of this agent in RA could be informative, according to Dr Zuraw.
“It would be interesting to see the performance of telitacicept in bDMARD [biologic disease modifying antirheumatic drug] refractory RA.”
Disclosures
Qing Zuraw, MD, MPH, MBA, reported that she is an employee of RemeGen Biosciences, Inc and owns company stock.