Anthera’s Blisibimod Phase 3 Trial Fails to Meet Primary Endpoint in Lupus Patients

Anthera Pharmaceuticals’ CHABLIS-SC1 Phase 3 clinical trial of its investigational therapy blisibimod did not meet its primary endpoint. After 52 weeks of treatment, there was no statistically significant clinical benefit for systemic lupus erythematosus (SLE) patients treated with the drug compared to placebo-treated patients.

Blisibimod acts by blocking BAFF, a B-cell activating factor crucial for various stages of B-cell development and life. The drug is a fusion between an antibody and a protein part capable of binding BAFF. Over-expression of BAFF is thought to play an important role in lupus development.

CHABLIS-SC1 (NCT01395745) enrolled 442 SLE patients in 12 countries throughout Asia, Eastern Europe, and Latin America. All patients were on corticosteroid treatment in addition to standard treatment, and were considered to have more severe lupus. Patients were randomized to receive either 200 mg blisibimod or a placebo. All patients continued using their standard medications during the trial.

The primary objective of the study was to evaluate the clinical effectiveness of blisibimod as measured by the Systemic Lupus Erythematosus Responder Index (SRI). An SRI is a composite measurement of three SLE assessment scales: the SELENA-SLEDAI, the Physician Global Assessment (PGA), and the British Isles Lupus Assessment Group (BILAG).

An SRI-6 responder is a patient who has achieved an improvement in SELENA-SLEDAI score of 6 or more points with no new lupus flares as measured by BILAG, and no worsening in their PGA score.

After 52 weeks of treatment, 47 percent of the blisibimod-treated patients and 42 percent of placebo-treated patients achieved an SRI-6 response. This difference was not considered statistically significant, Anthera reported. The effects of blisibimod treatment for SRI-4 and SRI-8 were also not statistically significant when compared to the placebo.

However, there was a statistically significant treatment effect on serum biological markers, including B-cells and immunoglobulins, consistent with the results seen in previous clinical trials in patients with lupus and IgA nephropathy (a kidney disease that occurs when an antibody called immunoglobulin A, or IgA, lodges in the kidneys, resulting in local inflammation that over time, may hamper the ability of kidneys to filter blood waste).

Concerning safety, treatment with blisibimod was well tolerated with no major adverse events reported.

“We are disappointed that the results did not demonstrate a meaningful improvement in patients’ disease activity as assessed by SRI endpoints,” William Shanahan, MD, Anthera’s chief medical officer, said in a press release, thanking the patients, investigators, and caregivers who made the CHABLIS-SC1 study possible.

“It has yielded significant amounts of data which we look forward to sharing with the scientific community in the future which we believe will help to further inform the development of treatments for severe lupus,” he added.

Anthera will continue to analyze the results of the trial in consultation with lupus specialists to determine the future of the blisibimod lupus program, including the ongoing CHABLIS 7.5 (NCT02514967) clinical trial evaluating the effectiveness of blisibimod on patients who continue to experience disease activity despite corticosteroid use.

Because the pharmacological effects on B-cells and immunoglobulins observed in CHABLIS-SC1 were as expected, the company will continue to develop blisibimod for patients with IgA nephropathy (IgAN) pending the 48-week results from the BRIGHT-SC (NCT02062684) study.

This ongoing Phase 2 clinical trial is evaluating the effectiveness and safety of subcutaneous blisibimod administration in addition to standard therapy in 57 patients with biopsy-proven IgAN.

Anthera will report 48-week results from the BRIGHT-SC IgAN clinical trial and topline data from the SOLUTION clinical trial later this year.

SOLUTION is a Phase 3 study (NCT02279498) evaluating the noninferiority of Sollpura compared to approved, porcine-derived, enterically-coated pancreatic enzyme replacement therapy when administered to patients with cystic fibrosis-related exocrine pancreatic insufficiency (the most common gastrointestinal complication of cystic fibrosis, a life-threatening lung disease).