September 4, 2018
The Lupus Research Alliance is disappointed with the results announced by AstraZeneca and MedImmune of the clinical trial testing the investigational drug anifrolumab for moderate to severe systemic lupus erythematosus (SLE). However, the knowledge gained from further analyzing these data will be invaluable in fully understanding the effects of anifrolumab and designing future studies.
Top-line results of the TULIP 1 trial reported that anifrolumab did not significantly reduce symptoms of lupus compared with placebo, when added to standard of care therapy. Anifrolumab is a monoclonal antibody that blocks type I interferons – proteins produced to fight outside invaders like bacteria. Data from mice and human studies have shown that type I interferons contribute significantly to the autoimmunity and inflammation that mark lupus. An estimated 60% – 80% of adult lupus patients have higher than average levels of type I interferon.
Background on TULIP
The earlier Phase 2 trial had provided promising results of the effectiveness of anifrolumab in reducing inflammation and thus reducing disease symptoms. Notably, a second Phase 3 trial of anifrolumab (TULIP 2) will provide additional insights when the data are available later this year.
“TULIP was a pioneering step because it specifically zeroed in on one important molecular pathway involved in lupus,” 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 NewYork-Presbyterian/Weill Cornell Medical Center. “When the full results are analyzed, it will be important to dissect the data in detail. Understanding the features of those patients who responded to anifrolumab as well as those who did not respond will be essential in helping us learn how the trial design may need to be adjusted to more precisely target patients who can benefit from this treatment approach.”
Dr. Crow continued, “It will also be important to determine whether the response to anifrolumab or placebo varied from one study site to another. Because of the complexity of lupus and the heterogeneity of symptoms among lupus patients it is particularly important for investigational drug studies to be conducted in the most consistent manner at all study sites.”
LuCIN Aims to Address Trial Challenges
To help address this issue, the Lupus Research Alliance developed the Lupus Clinical Investigators Network (LuCIN) of top research centers across the U.S. and Canada. Integrating a coherent network of highly trained investigators, LuCIN aims to provide uniform settings for trials that can deliver consistent results.
“People with lupus desperately need new treatments, and we will not stop until we can give them just that,” added Lupus Research Alliance President and CEO Kenneth M. Farber. “Through LuCIN and our comprehensive research grant programs, we are committed to advancing every aspect of the scientific process from discoveries in the lab through drug development and clinical trials to determine if a possible therapy is safe and effective.”
“Given the complexity of the disease, testing new treatments for lupus is a marathon, not a sprint,” noted Gerald Nepom, MD, PhD, Co-chair of the Lupus Research Alliance Scientific Advisory Board and Director of the Immune Tolerance Network sponsored by the National Institute of Allergy and Infectious Diseases. “We will learn from this trial and move forward better informed. It is important that despite setbacks, every member of the lupus community continues to support basic research into the causes of the disease as well as the clinical trial process as that is the only path to better treatments and a cure.”