European systemic lupus erythematosus (SLE) patients who produce autoantibodies against double-stranded DNA — a well-known biomarker of the disease — seem to benefit from the addition of Lupuzor (rigerimod) to their standard of care, new Phase 3 data suggest.
In fact, more patients receiving the investigational add-on therapy experienced a reduction in disease activity compared with standard of care alone — 71.1% versus 48.8%.
However, no such benefit was observed in U.S. patients or in those without autoantibodies against double-stranded DNA (anti-dsDNA).
Lupuzor, also known as IPP-201101, is being developed by ImmuPharma. It is a peptide-based therapy that inhibits self-reactive T-cells without affecting healthy immune cells. This mode of action makes Lupuzor an attractive therapeutic option.
The pivotal Phase 3 trial (NCT02504645) evaluated the safety and effectiveness of Lupuzor versus placebo as an add-on treatment to standard lupus therapy. The study, completed in January 2018, enrolled 200 lupus patients and was conducted in 30 clinical centers around the world.
Participants were randomly assigned to receive 200 micrograms of either Lupuzor under the skin or a placebo in addition to standard therapy every four weeks for 48 weeks.
The trial, however, failed its primary goal. While more patients experienced a reduction in disease activity with Lupuzor (52%) than with standard therapy alone (44.6%), the difference was not statistically significant.
In a previous analysis, researchers focused on patients in the study who were positive for anti-dsDNA antibodies. Up to 70% of lupus patients have these autoantibodies, which contribute to more severe disease activity.
In this population, Lupuzor showed a superior response rate (61.5%) compared with standard therapy (47.3%), but, again, this difference was not statistically significant.
This new analysis comparing patients with anti-dsDNA antibodies from the European and U.S. groups shows that Lupuzor significantly benefited patients in Europe versus standard therapy — 71.1% vs. 48.8% — but not those in the U.S. — 35.7% vs. 42.8%.
These contrasting results may be due to a variety of different factors between the two groups that require additional investigation, the researchers said.
Investigators also found that patients who were negative for anti-dsDNA autoantibodies showed no benefit from Lupuzor, suggesting that the therapeutic activity of the treatment could be linked to these autoantibodies. Thus, this biomarker could help identify patients most likely to benefit from the add-on therapy.
“We believe these additional results in Antibody Positive patients are of great value,” said Robert Zimmer, MD, PhD, chief scientific officer of ImmuPharma, said in a press release. “The potential efficacy of Lupuzor seems to be correlated with the presence of anti-dsDNA auto-antibodies, a biomarker for Lupus, and we hope to confirm that Lupuzor will come to be considered as a disease modifying agent.”
“We believe this is in line with what healthcare practitioners are seeking: precision medicines to target therapies, using biomarkers that reference precisely those patients who could benefit from the treatment options available. This should reduce healthcare costs and improve patient outcomes,” he said.
ImmuPharma will continue to review the Phase 3 data to fully address the effects of Lupuzor as an add-on treatment in lupus patients.
The company is now recruiting patients for an extension study, which is expected to provide more valuable information on Lupuzor’s effectiveness and safety.
“In this study Lupuzor has demonstrated a superior response rate over placebo and confirmed its exceptional safety profile,” said Tim McCarthy, chairman of ImmuPharma. “We continue to believe Lupuzor has the potential to bring a much needed treatment to Lupus sufferers around the world. We look forward to providing our shareholders with further updates as we move forward with this programme.”