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Posted by on Nov 2, 2009 in Pharma, Rheumatology

Second Belimumab Trial Delivers, Sort Of

Second Belimumab Trial Delivers, Sort Of

Lupus.jpg

Another phase 3 trial of belimumab (Benlysta; Human Genome Sciences/GSK) in patients with systemic lupus erythematosus (SLE) has met its primary endpoint, according to a company press release. These data complement results of a previous phase 3 study, BLISS-52, in which the mAb (when compared with placebo) significantly improved disease activity* at 1 year.

Combined trial data will undoubtedly be used to support a biologics license application (BLA) to the FDA. Neither phase 3 study, however, has been published in a peer-reviewed journal.

In the placebo-controlled BLISS-76, belimumab 10 mg/kg significantly improved the SLE Responder Index** at 52 weeks (43.2% vs 33.8% with placebo; P = .021). However, the 1-mg/kg dose was not associated with statistically significant improvement. Outcomes of several secondary endpoints (eg, Physician’s Global Assessment, reduction of corticosteroid dosage, SF-36 Physical Component Summary) also did not reach statistical significance.

Serious or severe infections were observed in 7.2% of patients who received belimumab and 8.0% of patients who received placebo. Rates of serious or severe infusion reactions were 1.1% with belimumab and 0.7% with placebo. Rates of discontinuation due to adverse events were 7.2% with belimumab and 7.6% with placebo. A handful of malignancies and deaths were also reported.

A comparison of the BLISS-52 and BLISS-76 results is provided here:

Outcome

BLISS-52

BLISS-76

Primary endpoint (52 weeks)


(1 and 10 mg/kg)


(10 mg/kg only)

   Belimumab 10 mg/kg, %

57.6

43.2

   Belimumab 1 mg/kg, %

51.7

        40.6 (NS)

   Placebo, %

43.6

33.8

Secondary endpoints

Reduction of SELENA SLEDAI score


(1 and 10 mg/kg)


(10 mg/kg only)

   Belimumab 10 mg/kg, %

58.3

46.9

   Belimumab 1 mg/kg, %

53.1

        42.8 (NS)

   Placebo, %

46.0

35.6

Improvement in PGA


(10 mg/kg only)

NS

Reduction of corticosteroid dosage (≥25% to ≤7.5 mg/d)


(1 and 10 mg/kg)

NS

SF-36 Physical Component Summary

NS

NS

Adverse events

Serious infections

 

 

   Belimumab, %

6.1

7.2

   Placebo, %

5.9

8.0

Infusion reactions

 

 

   Belimumab, %

N/A

1.1

   Placebo, %

N/A

0.7

Discontinuation

 

 

   Belimumab, %

N/A

7.2

   Placebo, %

N/A

7.6

Per protocol, BLISS-76 will continue for another 24 weeks, and according to the CEO of HGS, a BLA will likely be submitted to the FDA in the first half of next year.

Belimumab is a human mAb that inhibits the activity of B-lymphocyte stimulator (BLyS), which promotes the survival of (auto)antibody-producing B cells. The drug was discovered by HGS, which entered into a codevelopment and comarketing agreement with GSK in 2006. Other anti-B-cell therapies in clinical development for SLE include epratuzumab (Immunomedics) and ocrelizumab (Genentech, Biogen), aka Son of Rituxan.

A recent great hope for SLE, mycophenolate mofetil (CellCept; Roche) died a death of noninferiority after it performed no better than cyclophosphamide in the induction treatment of lupus nephritis. Rituximab (Rituxan) also flopped in a recent phase 3 study of lupus nephritis.

According to the Lupus Foundation of America, roughly 1.5 million Americans and more than 5 million people worldwide have lupus.

mAb = monoclonal antibody; N/A = not available; NS = not significant.

* Measured by using a combination of 4 recognized scales: a reduction of the SELENA SLEDAI score by at least 4 points from baseline; no worsening per the Physician’s Global Assessment (PGA); no new BILAG-A organ domain score; and no more than 1 new BILAG-B organ domain score.

** The SLE Responder Index defines patient response as an improvement in the SELENA SLEDAI score by at least 4 points and no clinically significant decline per the BILAG score or PGA.

bmartin (1127 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.