April 11, 2019
The Lupus Research Alliance is pleased to share the results from four clinical trials presented at LUPUS 2019. These studies continue to push our way forward toward new and improved treatments to help the lupus community.
There’s a Silver Lining in New Belimumab Results
Jim Oates, MD, Medical University of South Carolina, presented the results announced by GSK at LUPUS 2019 for the EMBRACE clinical trial that tested the approved drug Benlysta® (belimumab) in black patients with systemic lupus erythematosus (SLE), individuals who can be severely affected by the disease. The primary endpoint of this study – response to the drug as evaluated by a widely accepted index of disease activity – was not achieved. However, according to scientific advisors to the Lupus Research Alliance, the results may hold lessons for clinical trial design and suggest opportunities for future informative studies. The data showed that patients with well-documented active disease experienced significant improvements in several parameters. In addition, the safety profile in EMBRACE was consistent with the safety profile in other belimumab clinical trials. As in other clinical trials of potential lupus therapies, research to characterize those patients who responded to the drug can inform future trial design and patient management.
Lupus occurs more frequently and with greater severity among people of black heritage or descent. As study investigators noted, “the efficacy and safety of intravenous (IV) belimumab has been demonstrated in several Phase 2/3 studies; however, the small number of black patients within these trials, and the conflicting results, have limited conclusions regarding efficacy in this population.” The EMBRACE study aimed to assess the effectiveness and safety of intravenous belimumab plus standard of care for black patients with active lupus.
“If trials were designed so there is confidence that the enrolled patients have significant lupus-related disease activity, perhaps there would be more positive results,” noted Mary Crow, MD, co-chair of the Lupus Research Alliance Scientific Advisory Board as well as Physician-in-Chief and Chair of the Department of Medicine at Hospital for Special Surgery and Chief of the Division of Rheumatology at HSS and New York-Presbyterian/Weill Cornell Medical Center. “It is important to note that some improvements were seen in subgroups of patients, particularly those with more active disease. Companies working on new treatments for lupus can learn from these results and adjust future trials to optimize opportunities to get a significant result.”
“The EMBRACE trial represents important clinical research as it paves the way for greater diversity in lupus trials” added Lupus Research Alliance Research Director Teodora Staeva, PhD. “As this and other trials have shown, the heterogeneity of lupus patients is a core issue in lupus that necessitates a highly targeted approach to treatment. The results confirm our organization’s research strategy to focus on understanding differences in disease mechanisms among patients so we can provide the right therapy to the right patient.”
Ustekinumab (Stelara®) Shows Effectiveness in Lupus
A Phase 2 controlled study compared the investigational monoclonal antibody ustekinumab (Stelara®) with placebo among patients with active lupus. Investigators had previously reported greater improvement with Stelara® vs placebo in several common measures of disease activity through six months. Results presented at LUPUS2019 showed similar improvements through one year. Improvement in disease activity as measured by a standard lupus index was significantly greater among patients treated with Stelara (62%) than those who received placebo (33%).
Stelara® is approved by the FDA as a treatment for psoriasis, psoriatic arthritis, and Crohn’s disease. In this lupus study, Stelara’s safety was similar as when used for these other conditions. The Phase 3 trial is underway and is being conducted worldwide and through the Lupus Research Alliance Lupus Clinical Investigators Network (LuCIN) in sites across North America. Presented previously at the 2018, American College of Rheumatology annual meeting this study was sponsored by Janssen Research & Development, LLC.
The Lupus Research Alliance is particularly excited about this study having first identified the potential of Stelara® as a possible treatment for lupus and requested that Janssen test its use in people with lupus.
Baricitinib Significantly Improved Lupus Symptoms of Arthritis and/or Rash
Maria Silk, PharmD at Eli Lilly and Company presented positive results previously reported at EULAR 2018 of a Phase 2, randomized, double-blind, placebo-controlled study testing baricitinib for patients with SLE receiving standard therapy.
Baricitinib is approved as a treatment for another autoimmune disease, rheumatoid arthritis in more than 50 countries, including the United States.
The primary endpoint of the study was met — significant improvement in either arthritis or rash as defined by a standard measurement of lupus symptoms. At six months, arthritis or rash was resolved in 67% of patients treated with baricitinib compared with 53% of those receiving placebo plus standard care. In addition, significant more patients treated with baricitinib (64%) achieved an improvement in lupus disease activity according to a widely used measurement index versus 48% of those on placebo. The proportion of patients who experienced a reduction in flares, Lupus Low Disease Activity, improvements according to a global physician assessment and reduced tender joint count were also significantly improved among those who received baricitinib; however, the actual improvements for these measurements were not statistically significant between the two patient groups.
Investigators concluded that once-daily oral baricitinib plus standard care was associated with significant clinical improvements compared to placebo as well as an acceptable benefit/risk profile. “These findings support further study of baricitinib as a potential therapy for patients with SLE.”
IFN-K Shows Mixed Results in Phase 2 Trial
Frédéric Houssiau, MD, PhD of Université Catholique de Louvain reported the results of an international multicenter Phase 2 trial testing IFN-K (IFNα Kinoid) as a potential treatment for moderate to severe systemic erythematosus lupus. IFN-K is quite different from other agents in development targeting the Type I IFN pathway in lupus. It is a type of vaccine that stimulates production of antibodies that can neutralize excess interferon and block the ability to activate subsequent inflammation.
Sponsored by Neovacs, the trial met one of its primary co-endpoints, showing that IFN-K triggered the production of antibodies that neutralize interferon in 91% of patients and significantly reduced the interferon gene signature – meaning that the activity of genes controlled by interferon went down. Interferon signature genes have been shown to be elevated in people with lupus, particularly when the disease is active. The other primary co-endpoint, measure of lupus disease activity, did not find benefit when comparing patients treated with IFN-K versus those receiving placebo.
Dr. Houssiau also reported that a Lupus Low Disease Activity State was achieved in more patients treated with IFN-K than placebo and that the level of treatment with corticosteroids was able to be reduced in a significant number of patients. IFN-K was shown to be well-tolerated.
Dr. Houssiau concludes that these results warrant further investigation in a Phase 3 trial.
Lupus Research Alliance Research Director Teodora Staeva, PhD commented, “Safer, more effective treatments in lupus are urgently needed, and the results of these trials bring hope that potential therapies are in the wings. We look forward to seeing additional results as these agents are further studied in trials with larger groups of patients.”