“We are experiencing unprecedented trial activity in lupus”, commented Richard Furie, MD, addressing scientists, physicians and patient advocates at the American College of Rheumatology (ACR) annual scientific conference going on this week in Boston. Results of several clinical trials were presented at sessions dedicated to new lupus treatments.
Positive Results with Interferon Inhibitor
The efficacy and safety of a novel monoclonal antibody targeting interferon, sifalimumab [Abstract], were assessed in a mid-stage study in patients with moderate to severe SLE. Interferon is a protein involved in inflammation. The study evaluated 431 patients receiving monthly treatment with either their current standard of care plus placebo or plus sifalimumab at one of three doses. After one year of treatment, significantly more patients reported improvement who were treated with sifalimumab at all doses versus those given placebo plus their standard of care. Side effects were mostly similar among those treated with placebo versus sifalimumab. However, more patients reported infections, particularly at the highest dose of sifalimumab.
MedImmune is also developing an inhibitor of the interferon receptor, anifrolumab, for lupus, and early data presented at ACR, suggests this drug may be more effective than sifalimumab [Abstract].
Pediatric Lupus Patients Respond Well to Belimumab
Results were promising from the first multicenter study looking at the use of GSK’s belimumab (Benlysta) [Abstract] in children. The human monoclonal antibody that inhibits soluble B-lymphocyte activating factor (BAFF) was approved by the FDA in 2011 for treatment of lupus in adults. Patients who develop lupus as children tend to have more severe disease requiring more aggressive immunosuppression than adult SLE. The observational study led by investigators at Columbia University Medical Center tracked the progress of patients with SLE diagnosed before their 19thbirthday and treated with belimumab from 10 large academic centers. Of 38 pediatric patients, 71% responded well to belimumab within six months. Steroids were tapered in 63% of the pediatric patients, and discontinued in 22%.
Ups and Downs for Anti-Interleukin-6 Therapies
Daniel Wallace MD, reported results of a Phase 2 trial of Pfizer’s interleukin-6, IL-6 neutralizing monoclonal antibody PF-04236921 [Abstract] in patients with active SLE. IL-6 is a protein involved in regulating inflammation and immune responses, and is found at abnormally high levels in the blood of lupus patients. Over six months, 183 SLE patients received either placebo or PF-04236921 at one of three doses. The experimental compound was shown to significantly reduce severe flares and seemed to be more effective in patients with higher disease activity. Safety was acceptable at the two lower doses; the higher dose was discontinued due to infection-related safety concerns. Dr. Wallace concluded that the results show an acceptable safety profile and that additional clinical study is warranted.
Results from a much smaller Phase 2 proof of concept trial of Janssen’s IL-6 inhibitor sirukumab [Abstract] in lupus nephritis were less encouraging. The 6 month study in 25 patients did not show a significant improvement in disease and almost half of the subjects had an infection-related adverse event.
Tabalumab Phase 3 Results Unveiled
A late breaking presentation shared results of two Phase 3 studies of tabalumab in treating lupus. Tabalumab is a human monoclonal antibody that neutralizes a B-cell activating factor (BAFF), which is also the target of approved lupus treatment belimumab.
Both trials evaluated the effectiveness and safety of treatment for one year with tabalumab plus standard of care at varying week intervals compared to placebo plus standard of care among over 2,000 patients with active, moderate-to-severe SLE. The primary measurement of efficacy was the proportion of patients who showed significant improvement in symptoms as measured by a standard evaluation tool. By this measurement, improvement was not shown in trial 1, but was in the second Phase 3 trial among patients who were treated with a higher dose of tabalumab every two weeks. Secondary endpoints measuring whether corticosteroids could be reduced, the length of time patients went without having a severe flare and a reduction in the degree of fatigue were not statistically significant in either study. Serious side effects were similar between all groups of patients including those that received placebo.
Based on the results of these two trials, Lilly discontinued development of tabalumab for SLE.
“Frustratingly, given that one of the trials met its primary endpoint and there were encouraging signs in the other, it is very disappointing that Lilly have decided to pull out of further lupus trials of this treatment”, said LRI Scientific Advisory Board member and advisor on the tabalumab trials, David Isenberg, MD. “In spite of this decision, these data do support that blocking BAFF may be helpful in the treatment of lupus.”