Belimumab Shows Efficacy in Second Lupus Trial

Significantly more lupus patients responded to belimumab than placebo in a randomized trial with more than 800 patients followed for a year, the second positive outcome from a pivotal trial of the investigational monoclonal antibody in lupus this year.

After successfully meeting the primary end point in two large, separate lupus-treatment trials, Human Genome Sciences and GlaxoSmithKline, the two companies jointly developing belimumab (Benlysta), plan to file a new drug application with the Food and Drug Administration during the first half of 2010, said H. Thomas Watkins, president of HGS, during a conference call for investors.

If approved, it would be the first drug to receive a labeled indication for lupus in more than 50 years. Belimumab acts by blunting B-cell activity.

Initial results for the more recent of the two pivotal trials, the Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-76 study, were announced by HGS and GlaxoSmithKline in a press release, with a full report of the findings expected next summer. Initial results from the first pivotal trial, BLISS-52, were first released last July.

The primary outcome benefit from belimumab treatment was “solid,” said Dr. Joan T. Merrill, a specialist in treating systemic lupus erythematosus (SLE) who was a co-investigator on BLISS-76.

“The lupus community has waited decades for one positive phase III trial of an investigational drug developed for lupus. Now we have two.” Belimumab “may emerge as a significant new treatment for lupus,” said Dr. Merrill, professor of medicine at the University of Oklahoma Health Sciences Center in Oklahoma City. Dr. Merrill has served as a consultant to and has received research funding from HGS and GlaxoSmithKline as well as from several other drug companies.

BLISS-76 randomized 819 patients at 136 sites in 19 countries in North America and Europe. Enrollment criteria were not released for this study, but the similarly designed BLISS-52 trial included SLE patients with a score of 6 or more on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA SLEDAI). Patients also had to be seropositive for at least either antinuclear antibody at a level of 1:80 or greater or for anti–double stranded DNA at a level of 30 IU/mL or greater.

Patients were randomized to 1 mg/kg intravenous belimumab, 10 mg/kg intravenous belimumab, or placebo. Treatment occurred on days 0, 14, 28, and then every subsequent 28 days for 1 year. The study's primary end point was the percent of patients meeting the SLE Responder Index (SRI) after 52 weeks of treatment.

In BLISS-76 the SRI end point was reached by 43% of patients on the 10 mg/kg dosage, 41% of patients receiving 1 mg/kg, and 34% of patients on placebo. The difference in the outcome rate was statistically significant between the 10-mg/kg arm and placebo, but not between the 1-mg/kg arm and placebo. In BLISS-52, the rate of SRI responses at 52 weeks was 58% with the 10-mg/kg regimen compared with 44% in patients on placebo, also a statistically significant difference. The 10-mg/kg dosage is the one that HGS will pursue in its FDA filing, company officials said.

The safety profile of belimumab looked good in this study, as it had in BLISS-52, with no significant difference in the rates of malignancies, deaths, infections, serious infections, total adverse events, or serious adverse events among the treatment groups.

Significantly more lupus patients responded to belimumab than placebo in a randomized trial with more than 800 patients followed for a year, the second positive outcome from a pivotal trial of the investigational monoclonal antibody in lupus this year.

After successfully meeting the primary end point in two large, separate lupus-treatment trials, Human Genome Sciences and GlaxoSmithKline, the two companies jointly developing belimumab (Benlysta), plan to file a new drug application with the Food and Drug Administration during the first half of 2010, said H. Thomas Watkins, president of HGS, during a conference call for investors.

If approved, it would be the first drug to receive a labeled indication for lupus in more than 50 years. Belimumab acts by blunting B-cell activity.

Initial results for the more recent of the two pivotal trials, the Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-76 study, were announced by HGS and GlaxoSmithKline in a press release, with a full report of the findings expected next summer. Initial results from the first pivotal trial, BLISS-52, were first released last July.

The primary outcome benefit from belimumab treatment was “solid,” said Dr. Joan T. Merrill, a specialist in treating systemic lupus erythematosus (SLE) who was a co-investigator on BLISS-76.

“The lupus community has waited decades for one positive phase III trial of an investigational drug developed for lupus. Now we have two.” Belimumab “may emerge as a significant new treatment for lupus,” said Dr. Merrill, professor of medicine at the University of Oklahoma Health Sciences Center in Oklahoma City. Dr. Merrill has served as a consultant to and has received research funding from HGS and GlaxoSmithKline as well as from several other drug companies.

BLISS-76 randomized 819 patients at 136 sites in 19 countries in North America and Europe. Enrollment criteria were not released for this study, but the similarly designed BLISS-52 trial included SLE patients with a score of 6 or more on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA SLEDAI). Patients also had to be seropositive for at least either antinuclear antibody at a level of 1:80 or greater or for anti–double stranded DNA at a level of 30 IU/mL or greater.

Patients were randomized to 1 mg/kg intravenous belimumab, 10 mg/kg intravenous belimumab, or placebo. Treatment occurred on days 0, 14, 28, and then every subsequent 28 days for 1 year. The study's primary end point was the percent of patients meeting the SLE Responder Index (SRI) after 52 weeks of treatment.

In BLISS-76 the SRI end point was reached by 43% of patients on the 10 mg/kg dosage, 41% of patients receiving 1 mg/kg, and 34% of patients on placebo. The difference in the outcome rate was statistically significant between the 10-mg/kg arm and placebo, but not between the 1-mg/kg arm and placebo. In BLISS-52, the rate of SRI responses at 52 weeks was 58% with the 10-mg/kg regimen compared with 44% in patients on placebo, also a statistically significant difference. The 10-mg/kg dosage is the one that HGS will pursue in its FDA filing, company officials said.

The safety profile of belimumab looked good in this study, as it had in BLISS-52, with no significant difference in the rates of malignancies, deaths, infections, serious infections, total adverse events, or serious adverse events among the treatment groups.

Significantly more lupus patients responded to belimumab than placebo in a randomized trial with more than 800 patients followed for a year, the second positive outcome from a pivotal trial of the investigational monoclonal antibody in lupus this year.

After successfully meeting the primary end point in two large, separate lupus-treatment trials, Human Genome Sciences and GlaxoSmithKline, the two companies jointly developing belimumab (Benlysta), plan to file a new drug application with the Food and Drug Administration during the first half of 2010, said H. Thomas Watkins, president of HGS, during a conference call for investors.

If approved, it would be the first drug to receive a labeled indication for lupus in more than 50 years. Belimumab acts by blunting B-cell activity.

Initial results for the more recent of the two pivotal trials, the Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-76 study, were announced by HGS and GlaxoSmithKline in a press release, with a full report of the findings expected next summer. Initial results from the first pivotal trial, BLISS-52, were first released last July.

The primary outcome benefit from belimumab treatment was “solid,” said Dr. Joan T. Merrill, a specialist in treating systemic lupus erythematosus (SLE) who was a co-investigator on BLISS-76.

“The lupus community has waited decades for one positive phase III trial of an investigational drug developed for lupus. Now we have two.” Belimumab “may emerge as a significant new treatment for lupus,” said Dr. Merrill, professor of medicine at the University of Oklahoma Health Sciences Center in Oklahoma City. Dr. Merrill has served as a consultant to and has received research funding from HGS and GlaxoSmithKline as well as from several other drug companies.

BLISS-76 randomized 819 patients at 136 sites in 19 countries in North America and Europe. Enrollment criteria were not released for this study, but the similarly designed BLISS-52 trial included SLE patients with a score of 6 or more on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA SLEDAI). Patients also had to be seropositive for at least either antinuclear antibody at a level of 1:80 or greater or for anti–double stranded DNA at a level of 30 IU/mL or greater.

Patients were randomized to 1 mg/kg intravenous belimumab, 10 mg/kg intravenous belimumab, or placebo. Treatment occurred on days 0, 14, 28, and then every subsequent 28 days for 1 year. The study's primary end point was the percent of patients meeting the SLE Responder Index (SRI) after 52 weeks of treatment.

In BLISS-76 the SRI end point was reached by 43% of patients on the 10 mg/kg dosage, 41% of patients receiving 1 mg/kg, and 34% of patients on placebo. The difference in the outcome rate was statistically significant between the 10-mg/kg arm and placebo, but not between the 1-mg/kg arm and placebo. In BLISS-52, the rate of SRI responses at 52 weeks was 58% with the 10-mg/kg regimen compared with 44% in patients on placebo, also a statistically significant difference. The 10-mg/kg dosage is the one that HGS will pursue in its FDA filing, company officials said.

The safety profile of belimumab looked good in this study, as it had in BLISS-52, with no significant difference in the rates of malignancies, deaths, infections, serious infections, total adverse events, or serious adverse events among the treatment groups.