Vor Bio Announces Positive Phase 3 Results of Telitacicept in Systemic Lupus Erythematosus Published in NEJM

Analysis reveals significant industry trends and economic implications

Release Date

2025-10-17

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Vor Bio announces the publication of positive results from a Phase 3 trial in China evaluating telitacicept for systemic lupus erythematosus (SLE) in The New England Journal of Medicine. The trial, sponsored by RemeGen Co., Ltd., met its primary endpoint, demonstrating a statistically significant improvement in disease activity compared to placebo. Telitacicept, a dual BAFF/APRIL inhibitor, showed a 67.1% response rate versus 32.7% with placebo. The drug is approved in China for SLE, rheumatoid arthritis, and generalized myasthenia gravis. A global Phase 3 trial in gMG is underway to support potential approval in the United States, Europe, and Japan.

Key Highlights

  • Phase 3 trial of telitacicept in SLE met primary endpoint with statistically significant improvement in disease activity.
  • 67.1% of patients responded to telitacicept versus 32.7% to placebo.
  • Dual inhibition of BAFF and APRIL validated as a transformative B-cell approach.
  • Telitacicept is approved in China for SLE, rheumatoid arthritis, and generalized myasthenia gravis.

Incidence and Prevalence

Global Estimates of Systemic Lupus Erythematosus Incidence and Prevalence

Prevalence Estimates

The prevalence of systemic lupus erythematosus (SLE) varies considerably by geographic location and study methodology. Generally, SLE prevalence is estimated between 15 and 50 per 100,000 individuals globally, with significant regional variations.

In the United States, a 2020 study found a prevalence of 241 per 100,000 people based on self-reported diagnoses. The UK showed an increase in prevalence from 64.99 per 100,000 in 1999 to 97.04 per 100,000 in 2012.

Asian countries typically report prevalence rates within 30-50 per 100,000 population, with some variations. Shanghai showed a higher prevalence of 70 per 100,000, while India, Japan, and Saudi Arabia reported lower rates of 3.2-19.3 per 100,000.

In Taiwan, the overall prevalence of SLE in 2011 was 8.11 per 10,000 people (equivalent to 81.1 per 100,000), with 14.3 per 10,000 in females and 1.62 per 10,000 in males.

Estonia reported a period prevalence between 39 and 48 per 100,000 and a point prevalence of 37-40 per 100,000 as of January 1, 2011.

In northwestern Spain, the overall age-adjusted SLE prevalence was 17.5 per 100,000 population aged 15 years and older, with higher rates in women (29.2 per 100,000) than men (5.8 per 100,000).

Incidence Rates

The incidence of SLE also shows significant geographic variation. In Taiwan, the overall incidence rate was 0.74-1 per 10,000 person-years (7.4-10 per 100,000), with 1.09-1.76 per 10,000 in females and 0.12-0.25 per 10,000 in males.

A UK study using the Clinical Practice Research Datalink found an incidence of 4.91 per 100,000 person-years during 1999-2012, with an annual 1.8% decline.

In Estonia, the incidence rate was between 1.5 and 1.8 per 100,000 person-years.

Another study reported a much lower incidence between 1994 and 2003 at 0.29 per 100,000 population, increasing to 0.49 per 100,000 between 2004 and 2013, with a peak in 2010 of 1.35 per 100,000.

In northwestern Spain, the age- and sex-adjusted annual incidence rate over a 20-year period was 3.6 per 100,000 population aged 15 years and older.

For childhood SLE, incidence ranges from 3.3 to 8.8 per 100,000 children, with higher Asian preponderance.

Demographic Patterns

SLE shows consistent demographic patterns across regions:

  • Female predominance with a female to male ratio of 9:1 in some studies, and generally reported as six times more common in women
  • Racial and ethnic disparities with increased prevalence in African-American, Afro-Caribbean, Native American, Asian Indian, Polynesian and Chinese populations compared to people of European descent
  • In the UK, highest rates were seen in Afro-Caribbeans (207 per 100,000), followed by Asians (48.8 per 100,000), and then Whites (20.3 per 100,000)
  • SLE is reportedly more common and more severe in people of African and Asian extraction living in industrialized countries

These global estimates highlight the significant variation in SLE epidemiology across different populations and regions.

Emerging End Points

Key Endpoints Emerging for Systemic Lupus Erythematosus

Recent publications highlight several key clinical endpoints that have evolved with therapeutic developments in Systemic Lupus Erythematosus (SLE) assessment:

The SLE Responder Index (SRI) remains important, with SRI(4) serving as a primary endpoint in trials like TULIP-1. The Modified SRI(6) has been used as a secondary endpoint. In a phase 2 trial of iberdomide, 54% of patients in the 0.45-mg group achieved SRI-4 response compared to 35% in the placebo group.

The British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) has emerged as a critical endpoint, becoming the primary endpoint in the TULIP-2 trial after TULIP-1 failed to meet SRI(4) endpoints. A BICLA response requires reduction in moderate-to-severe baseline disease activity with no worsening across nine organ systems.

The Lupus Low Disease Activity State (LLDAS) has been validated as a clinically meaningful endpoint associated with protection against flare and damage accrual. LLDAS is defined as SLEDAI-2K score ≤4, Physician Global Assessment (PGA) ≤1, and prednisolone ≤7.5 mg/day. Patients with at least 50% of observed time in LLDAS showed reduced risk of damage accrual (HR 0.54) and flare (HR 0.41).

Definitions of Remission in SLE (DORIS) has established criteria for remission, defined as clinical SLEDAI-2K score 0, PGA <0.5, and prednisolone ≤5 mg/day.

Sustained reduction of oral corticosteroids (typically to <7.5 mg/day or <10 mg/day) is increasingly recognized as a critical endpoint reflecting steroid-sparing effects and minimization of treatment-related toxicity.

For skin manifestations, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) responses, particularly ≥50% reduction in scores, are standard assessments.

Patient-reported outcomes (PROs) have gained importance. The SLE Symptom Severity Diary (SSD) and SLE Impact Questionnaire (SIQ) were developed in accordance with FDA PRO Guidance. The SSD contains 17 items assessing symptoms using an 11-point numeric response scale, while the SIQ contains 50 items to assess disease impacts using a 5-point Likert scale.

The Lupus Multivariable Outcome Score (LuMOS 2.0) has been developed to optimize discrimination between actively treated patients and those on placebo, detecting significantly greater treatment effects compared with the SRI-5.

Biomarkers are emerging as important endpoints: - Metabolite profiling for mechanism exploration and novel biomarker discovery - Serological, urinary, and cerebrospinal fluid biomarkers for assessing organ involvement - CD8 memory T cells as indicators of treatment response - Inflammatory markers related to cardiovascular disease risk

Type I interferon gene signature status is increasingly used for patient stratification in trials, particularly for therapies targeting the interferon pathway.

The annualized flare rate continues to be used to evaluate disease stability over time, while the EULAR/ACR criteria score has shown predictive value for disease severity.

Drugs with Similar Mechanism of Action as Telitacicept

Based on the available information, Telitacicept is a novel recombinant fusion protein that functions as a BLyS/APRIL dual inhibitor. It works by binding to and neutralizing the activity of B-lymphocyte stimulator (BLyS/BAFF) and a proliferation-inducing ligand (APRIL), thereby suppressing the development and survival of plasma cells and mature B cells.

Other Drugs with Similar MoA

The information provided does not specifically mention other drugs in clinical trials that share the exact same mechanism of action as Telitacicept (dual BAFF/APRIL inhibition). While several B-cell targeting therapies are mentioned, they work through different mechanisms:

  • Belimumab: An anti-B-cell activating factor antibody that only targets BAFF/BLyS, not both BAFF and APRIL like Telitacicept
  • Rituximab (RTX): An anti-CD20 monoclonal antibody that depletes CD20+ B cells
  • BTK inhibitors (such as Tolebrutinib, Evobrutinib, and Rilzabrutinib): These work through Bruton's tyrosine kinase inhibition in B-cell receptor signaling pathways
  • Alemtuzumab: An anti-CD52 monoclonal antibody

Combination Therapy Approaches

While not identical to Telitacicept's MoA, there are intervention models involving combinations of B-cell targeting therapies:

  • Sequential therapy with Rituximab and Belimumab for refractory SLE

  • This approach combines CD20+ B cell depletion with BLyS inhibition

  • Clinical trials including SynBioSe and BEAT-LUPUS have shown this combination can reduce autoantibody levels and disease activity

  • Many patients achieved a lupus low disease activity state (LLDAS)

  • The ongoing SynBioSe-2 trial is investigating optimal use, sequencing, and safety

Telitacicept Clinical Development

Telitacicept was approved in China in March 2021 for the treatment of systemic lupus erythematosus (SLE) at a recommended dose of 160 mg/week subcutaneously. It is also being evaluated in clinical trials for other indications including:

  • IgA nephropathy
  • Multiple sclerosis
  • Myasthenia gravis
  • Neuromyelitis optica spectrum disorders
  • Rheumatoid arthritis
  • Sjögren's syndrome

However, specific details about the intervention models for these trials are not provided in the available information.