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SAN FRANCISCO – The anti-CD22 monoclonal antibody epratuzumab missed its primary and secondary endpoints in two phase III trials involving adults with moderate to severe systemic lupus erythematosus.
At week 48, patients who received epratuzumab and standard therapy fared no better than those who received standard care and placebo, said Dr. Megan E.B. Clowse, who is a rheumatologist and clinical researcher at Duke University in Durham, N.C. “Many additional exploratory analyses were performed, and we really did not find any difference among the groups that would reveal a set of patients that would benefit from this treatment,” she said in her presentation of the two trials at the annual meeting of the American College of Rheumatology.
The failed EMBODY 1 and EMBODY 2 trials were identically designed phase III, multicenter, double-blind, randomized, placebo-controlled studies of adults with moderate to severe systemic lupus erythematosus (SLE), based on at least four ACR criteria, who also tested positive for anti–double stranded DNA or antinuclear antibodies. Participants were required to have received corticosteroids for at least 5 days before enrollment at a stable dose equivalent to 5-60 mg/day of prednisone. Doses of immunosuppressants and antimalarials also had to be stable, and patients could not have antiphospholipid syndrome or a British Isles Lupus Activity Group (BILAG) A score involving the kidneys or central nervous system. Most patients had musculoskeletal or musculocutaneous disease activity at baseline, Dr. Clowse said.
The treatment groups received standard-of-care therapies plus intravenous epratuzumab at doses of 1,200 mg every other week or 600 mg every week for a cumulative dose of 2,400 mg per 12-week treatment cycle, followed by 8 weeks without infusion. The primary endpoint was the percentage of responders by 48 weeks, as assessed by the composite BILAG-based Combined Lupus Assessment (BICLA). The BICLA measures improvement in BILAG disease activity across all eight body systems, with no worsening in BILAG or other disease activity indexes at the same time point and no treatment failure at any time point. There were a total of 1,579 patients in both studies combined.
About two-thirds of patients completed each study, and lack of efficacy was the main reason for dropping out, Dr. Clowse said. The primary endpoint was about 40% for all groups in both trials. Secondary endpoints, including changes in corticosteroid use, physician’s global assessment of disease activity, patient’s global assessment of disease activity, and other physician-reported and patient-reported outcomes, also were similar among the groups, she said. About 40% of patients remained on their baseline dose of corticosteroids, while less than 20% were able to cut their dose by at least half.
Epratuzumab was associated with improved SLE disease activity in phase IIb trials, Dr. Clowse noted. The biologic’s phase III safety profile resembled that of phase IIb trials and other prior studies, with no new safety signals, she added. The most common adverse events were upper respiratory tract infection, urinary tract infection, headache, and nausea.
UCB Pharma funded the study. Dr. Clowse reported having received consulting fees from UCB Pharma. Twelve of 15 coinvestigators also reported financial relationships with UCB Pharma and a number of other pharmaceutical companies.
SAN FRANCISCO – The anti-CD22 monoclonal antibody epratuzumab missed its primary and secondary endpoints in two phase III trials involving adults with moderate to severe systemic lupus erythematosus.
At week 48, patients who received epratuzumab and standard therapy fared no better than those who received standard care and placebo, said Dr. Megan E.B. Clowse, who is a rheumatologist and clinical researcher at Duke University in Durham, N.C. “Many additional exploratory analyses were performed, and we really did not find any difference among the groups that would reveal a set of patients that would benefit from this treatment,” she said in her presentation of the two trials at the annual meeting of the American College of Rheumatology.
The failed EMBODY 1 and EMBODY 2 trials were identically designed phase III, multicenter, double-blind, randomized, placebo-controlled studies of adults with moderate to severe systemic lupus erythematosus (SLE), based on at least four ACR criteria, who also tested positive for anti–double stranded DNA or antinuclear antibodies. Participants were required to have received corticosteroids for at least 5 days before enrollment at a stable dose equivalent to 5-60 mg/day of prednisone. Doses of immunosuppressants and antimalarials also had to be stable, and patients could not have antiphospholipid syndrome or a British Isles Lupus Activity Group (BILAG) A score involving the kidneys or central nervous system. Most patients had musculoskeletal or musculocutaneous disease activity at baseline, Dr. Clowse said.
The treatment groups received standard-of-care therapies plus intravenous epratuzumab at doses of 1,200 mg every other week or 600 mg every week for a cumulative dose of 2,400 mg per 12-week treatment cycle, followed by 8 weeks without infusion. The primary endpoint was the percentage of responders by 48 weeks, as assessed by the composite BILAG-based Combined Lupus Assessment (BICLA). The BICLA measures improvement in BILAG disease activity across all eight body systems, with no worsening in BILAG or other disease activity indexes at the same time point and no treatment failure at any time point. There were a total of 1,579 patients in both studies combined.
About two-thirds of patients completed each study, and lack of efficacy was the main reason for dropping out, Dr. Clowse said. The primary endpoint was about 40% for all groups in both trials. Secondary endpoints, including changes in corticosteroid use, physician’s global assessment of disease activity, patient’s global assessment of disease activity, and other physician-reported and patient-reported outcomes, also were similar among the groups, she said. About 40% of patients remained on their baseline dose of corticosteroids, while less than 20% were able to cut their dose by at least half.
Epratuzumab was associated with improved SLE disease activity in phase IIb trials, Dr. Clowse noted. The biologic’s phase III safety profile resembled that of phase IIb trials and other prior studies, with no new safety signals, she added. The most common adverse events were upper respiratory tract infection, urinary tract infection, headache, and nausea.
UCB Pharma funded the study. Dr. Clowse reported having received consulting fees from UCB Pharma. Twelve of 15 coinvestigators also reported financial relationships with UCB Pharma and a number of other pharmaceutical companies.
SAN FRANCISCO – The anti-CD22 monoclonal antibody epratuzumab missed its primary and secondary endpoints in two phase III trials involving adults with moderate to severe systemic lupus erythematosus.
At week 48, patients who received epratuzumab and standard therapy fared no better than those who received standard care and placebo, said Dr. Megan E.B. Clowse, who is a rheumatologist and clinical researcher at Duke University in Durham, N.C. “Many additional exploratory analyses were performed, and we really did not find any difference among the groups that would reveal a set of patients that would benefit from this treatment,” she said in her presentation of the two trials at the annual meeting of the American College of Rheumatology.
The failed EMBODY 1 and EMBODY 2 trials were identically designed phase III, multicenter, double-blind, randomized, placebo-controlled studies of adults with moderate to severe systemic lupus erythematosus (SLE), based on at least four ACR criteria, who also tested positive for anti–double stranded DNA or antinuclear antibodies. Participants were required to have received corticosteroids for at least 5 days before enrollment at a stable dose equivalent to 5-60 mg/day of prednisone. Doses of immunosuppressants and antimalarials also had to be stable, and patients could not have antiphospholipid syndrome or a British Isles Lupus Activity Group (BILAG) A score involving the kidneys or central nervous system. Most patients had musculoskeletal or musculocutaneous disease activity at baseline, Dr. Clowse said.
The treatment groups received standard-of-care therapies plus intravenous epratuzumab at doses of 1,200 mg every other week or 600 mg every week for a cumulative dose of 2,400 mg per 12-week treatment cycle, followed by 8 weeks without infusion. The primary endpoint was the percentage of responders by 48 weeks, as assessed by the composite BILAG-based Combined Lupus Assessment (BICLA). The BICLA measures improvement in BILAG disease activity across all eight body systems, with no worsening in BILAG or other disease activity indexes at the same time point and no treatment failure at any time point. There were a total of 1,579 patients in both studies combined.
About two-thirds of patients completed each study, and lack of efficacy was the main reason for dropping out, Dr. Clowse said. The primary endpoint was about 40% for all groups in both trials. Secondary endpoints, including changes in corticosteroid use, physician’s global assessment of disease activity, patient’s global assessment of disease activity, and other physician-reported and patient-reported outcomes, also were similar among the groups, she said. About 40% of patients remained on their baseline dose of corticosteroids, while less than 20% were able to cut their dose by at least half.
Epratuzumab was associated with improved SLE disease activity in phase IIb trials, Dr. Clowse noted. The biologic’s phase III safety profile resembled that of phase IIb trials and other prior studies, with no new safety signals, she added. The most common adverse events were upper respiratory tract infection, urinary tract infection, headache, and nausea.
UCB Pharma funded the study. Dr. Clowse reported having received consulting fees from UCB Pharma. Twelve of 15 coinvestigators also reported financial relationships with UCB Pharma and a number of other pharmaceutical companies.
AT THE ACR ANNUAL MEETING
Key clinical point: Epratuzumab was no more effective than placebo in two phase III trials of adults with moderate to severe systemic lupus erythematosus.
Major finding: Rates of BICLA response at 48 weeks were similar for the epratuzumab and placebo groups, as were all secondary and exploratory endpoints.
Data source: EMBODY 1 and 2 were phase III, multicenter, randomized, double-blind, placebo-controlled studies involving 1,579 adults.
Disclosures: UCB Pharma funded the study. Dr. Clowse reported having received consulting fees from UCB Pharma. Twelve of 15 coinvestigators also reported financial relationships with UCB Pharma and a number of other pharmaceutical companies.
