Human Genome Sciences announces positive phase 2 LymphoStat-B results

Download PDF Copy

Reviewed

Nov 13 2007

Human Genome Sciences, Inc. has announced the presentation of Phase 2 clinical results demonstrating that LymphoStat-B (belimumab) achieved a sustained improvement in disease activity across multiple clinical measures, decreased the frequency of disease flares over time, and was well tolerated through 2.5 years on treatment in combination with standard of care in patients with active systemic lupus erythematosus (SLE).

The results will be the subject of an oral presentation today in Boston at the Annual Scientific Meeting of the American College of Rheumatology (ACR).

“SLE is a chronic disease, and patients need new therapies that provide durable efficacy with a favorable safety profile,” said Michelle A. Petri, M.D., M.P.H., Professor, Division of Rheumatology, Department of Medicine, Johns Hopkins University. “The Phase 2 results presented at ACR showed that the significant clinical benefit observed for LymphoStat-B in serologically active SLE patients at 52 weeks appears to be sustained through 2.5 years. We look forward to further evaluation of LymphoStat-B in larger Phase 3 studies, which are ongoing.”

A separate poster presentation of the safety profile of LymphoStat-B showed that LymphoStat-B was well tolerated in combination with SLE standard-of-care therapy during long-term exposure, with incidence rates of adverse events, serious adverse events, malignancies, infections and laboratory abnormalities remaining comparable to placebo or decreasing through 2.5 years of treatment (Merrill et al).

“The results through 2.5 years confirm and extend the results reported at Weeks 52 and 76,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. “At Week 52 in LymphoStat-B patients with active SLE, we saw significant reductions in SLE disease activity versus placebo as measured by the SELENA SLEDAI and BILAG indices, the Physician's Global Assessment, and, most importantly, by the response rate chosen as the primary efficacy endpoint of the Phase 3 trials. We are encouraged by the continued improvement in these patients, and by the improvement over time in patients crossing over from placebo to LymphoStat-B after 52 weeks. If the Phase 2 results are confirmed in our ongoing Phase 3 trials, we believe that LymphoStat-B could represent a breakthrough in the treatment of SLE.”

The primary objectives of the Phase 2 study were to evaluate the efficacy and safety of LymphoStat-B (belimumab) plus standard of care, versus placebo plus standard of care. A total of 449 patients with active SLE were randomized to receive one of three different doses of LymphoStat-B or placebo (1, 4 or 10 mg/kg) administered intravenously over a 52-week treatment period, in addition to standard-of-care therapy. At the end of 52 weeks, 345 patients chose to participate in an optional 24-week extension phase of the study, during which all patients received LymphoStat-B. At Week 76, 296 patients chose to remain on LymphoStat-B treatment in an open-label long-term continuation phase of the Phase 2 trial, in which all patients are receiving 10 mg/kg LymphoStat-B. As of October 1, 2007, 244 patients remained on LymphoStat-B treatment in the continuation study.

Key Findings to Date from the Phase 2 Study

In June 2006, HGS reported the 52-week results of the Phase 2 trial of LymphoStat-B in patients with SLE. The 52-week results demonstrated that LymphoStat-B significantly reduced disease activity versus placebo in patients with serologically active SLE across multiple clinical measures, exhibited clinically relevant biological activity, and appeared generally safe and well tolerated. Frequency and severity of adverse events were similar to placebo, with no increase at higher doses. Among the findings at Week 52 was a significantly improved response rate among serologically active patients, as defined by an improvement in SELENA SLEDAI score of 4 points or greater, no new BILAG A flare and no more than one new BILAG B flare, and no worsening in Physician's Global Assessment (46% for LymphoStat-B versus 29% for placebo, p<0.01). This combination of measures is the primary efficacy endpoint in the ongoing pivotal Phase 3 clinical trials.

The data presented today at ACR 2007 demonstrated that LymphoStat-B achieved sustained improvement or stabilization of SLE disease activity in serogically active patients through 2.5 years. LymphoStat-B also decreased the frequency of SLE disease flares in these patients over time. The overall incidence of adverse events and laboratory abnormalities remained stable or decreased from Week 52 to Week 128.

The evidence of sustained clinical effect in serologically active SLE patients from Week 52 to Week 128 includes:

An increase from 46% to 54% in the combined patient response rate selected as the primary efficacy endpoint of the Phase 3 trials. Among serologically active subjects who completed 128 weeks of treatment (n=175), 63% responded based on this measure of clinical effect.

An increase from 49% to 58% in the proportion of patients who had improvement in SLE disease activity, as measured by SELENA SLEDAI (>4-pt reduction).

A sustained improvement in the percentage of serologically active patients who experienced no new BILAG A organ flare and no more than one new BILAG B organ flare (92% at Week 52; 94% at Week 128).

A sustained improvement in the percentage of serologically active patients showing no worsening in SLE disease activity, as measured by the Physician's Global Assessment (<.03-pt worsening – 90% at Week 52 and 91% at Week 128).

A decrease over time in the overall frequency of SLE disease flares, and in the frequency of severe disease flares, in patients who remained on LymphoStat-B through 2.5 years, as measured by the SELENA SLEDAI SLE Flare Index.

Sustained response to LymphoStat-B therapy was independent of the type of autoantibody at baseline.

A separate poster presentation reported that LymphoStat-B also promoted progressive normalization of autoantibody, immunoglobulin and complement levels over 2.5 years of therapy in SLE patients (Stohl et al), including:

Stable reductions in immunoglobulins, with no increase in infections or infectious events over time.

Normalization of IgG in patients with elevated IgG at baseline; from 45% to 57% of patients with hypergammaglobulinemia at baseline normalized at Weeks 52-128.