Clinical Trials

Date: 2016-03-03

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in Lupus

Company: GSK (UK)

Product: Benlysta® (belimumab)

Action mechanism: monoclonal antibody. Benlysta® (belimumab) is a fully human recombinant monoclonal antibody directed against BLyS (B-lymphocyte stimulator) . It prevents the interaction of BLys with its three receptors and indirectly decreases the B-cell survival and production of autoantibodies.

Disease: systemic lupus erythematosus (SLE)

Therapeutic area: Autoimmune diseases

Country:

Trial details:

• This analysis pooled data from two ongoing open-label, long-term, continuation studies that enrolled 998 patients (MITT) who completed the parent Phase III studies, BLISS-52 (NCT00424476) and BLISS-76 (NCT00424476). The BLISS studies were large randomised, controlled, clinical trials that were pivotal in the regulatory approval of Benlysta2,3,4.
• BLISS-52 and BLISS-76 patients were randomised to belimumab 1 mg/kg, belimumab 10 mg/kg, or placebo plus SoC for 52 or 76 weeks. Patients in the long-term continuation studies were included regardless of whether they received 10 mg/kg or 1 mg/kg (unlicensed dose) belimumab in the BLISS studies. All patients receiving 1 mg/kg in the BLISS studies subsequently transitioned to 10 mg/kg in the continuation studies. The BLISS studies excluded patients who had active Central Nervous System (CNS) Lupus or who had severe lupus kidney disease, or who had active nephritis.
• At baseline (defined as prior to the first dose of belimumab), 940 (94.2%) patients were female, with a mean (SD) age of 38.7 (11.49) years and disease duration of 6.69 (6.24) years. Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) values were assessed every 48 weeks (yearly interval).
• Overall 427 (42.8%) patients withdrew. Of those who withdrew, ‘patient request’ was the most common reason (168, 16.8%); where provided, the two reasons most cited by patients were a desire to conceive and logistical reasons. Other common reasons for withdrawal were AEs (85, 8.5%), other (70, 7.0%) and investigator decision (48, 4.8%).

Latest news:

• • On March 3, 2016, GSK announced publication of a new long-term analysis showing that patients with moderate-to-severe systemic lupus erythematosus (SLE) treated with Benlysta® (belimumab) plus standard of care (SoC) over five years experienced low rates of organ damage progression, regardless of their baseline level of damage. Results from this analysis of two pooled, open-label, continuation studies published in Lupus, showed that for the primary endpoint (change in SLICC Damage Index [SDI] from baseline, a validated score to quantify organ damage, at study years 5-6), 85.1% patients had no change in organ damage and the mean change in SDI from baseline was 0.2 (0.48, n=403). In patients without organ damage at baseline, 87.6% had no change in SDI and the mean change was 0.2 (0.44, n=241). In patients with organ damage at baseline, 81.5% had no change in SDI and the mean change was 0.2 (0.53, n=162).The overall probability of patients maintaining their SDI score was 0.83 (95% confidence interval [CI]: 0.79, 0.86) and the median time to first worsening was 677 days (n=117).
• The long-term safety observed in the analysis was consistent with the known safety profile of Benlysta®. The majority (96.5%) of patients in the modified intent-to-treat population (MITT) experienced an adverse event (AE) any time post baseline. The incidence of AEs decreased from 87.4% to 52.7% during the study. 313 (31.4%) patients experienced a serious AE. Overall, 433 (43.4%) patients experienced a drug-related AE. The most commonly reported drug-related AEs were infections/infestations (282, 28.3%) and gastrointestinal disorders (139, 13.9%).Opportunistic infections were reported in 23 (2.3%) patients, four cases of which were serious, and herpes zoster infection was reported for 87 (8.7%) patients, seven cases of which were serious. 11 deaths occurred during the study period and three additional deaths occurred after study exit.
• This data is an interim analysis of two open-label, non-randomised, uncontrolled extension studies with no placebo (SoC) data for comparison.

Is general: Yes