The Alliance for Children’s Therapeutics (ACT) is developing safer, more effective pediatric treatments, starting with a potentially groundbreaking drug candidate for lupus nephritis and other autoimmune diseases.
These diseases strike when the immune system turns against a patient’s body, attacking its organs and tissues. In lupus, this triggers inflammation that can damage the heart, lungs, brain, kidneys and other vital organs. The best available treatment uses high doses of steroids and chemotherapy to suppress the immune system and stop its attacks. Unfortunately, this leaves patients more vulnerable to infections. And the treatments are so toxic that they increase a child’s risk of suffering from diabetes, osteoporosis and other serious conditions.
Life with lupus can often result in shuttling in and out of the hospital, enduring chemotherapy infusions and emergency treatment for infections a patient’s immune system is too weak to repel. Families can be paralyzed, as parents can become overcome with worry and could miss countless days of work tending to their child’s needs.
ACT is testing a new drug candidate, called dalazatide, that could be safer and more effective than today’s treatments for autoimmune diseases.
Dalazatide is KPI's and Kineta's lead clinical stage program. In 2013 a phase 1a, first-in-human safety study was completed. A multi-ascending dose Phase 1b study completed enrollment in 1q 2014. A randomized placebo controlled trial in plaque psoriasis was completed in 2015. Data from Phase 1 studies have so far indicated that dalazatide has a favorable safety profile and demonstrates clinical effectiveness. Dalazatide continues to show strong potential to treat an array of high need autoimmune diseases including psoriatic arthritis, multiple sclerosis, rheumatoid arthritis, lupus, asthma and type 1 diabetes mellitus.
Dalazatide was initially derived from sea anemone venom — now based on a synthetic version of the venom — and is designed to disable the specific immune cells that become overactive in children and teens with lupus, without affecting the rest of the immune system. Dalazatide has stopped nephritis and arthritis in in-vivo models with no side effects, and preclinical tests have shown it is safe in adults.
Now ACT is working to turn the drug candidate into a real-world treatment for children and teens. This starts with studies by Seattle Children’s Research Institute’s Dr. Anne Stevens along with Kineta and KPI researchers. Together, they are investigating how dalazatide impacts a serious complication of lupus: nephritis. In lupus nephritis, overactive immune cells cause kidney inflammation that can lead to kidney failure and, in some cases, death.
This research will lay the foundation for quickly launching a clinical research trial of dalazatide. If the drug candidate is effective, it will be a key step toward making dalazatide the first new lupus nephritis therapy to be approved by the Food and Drug Administration. And because dalazatide targets cells that are also key players in multiple sclerosis, rheumatoid arthritis and many other conditions, our work could potentially improve the lives of children affected with these conditions.
Dr. Anne Stevens Associate Professor and Principal Investigator, Seattle Children’s Research Institute’s Center for Immunity and Immunotherapies
Dr. Stevens is associate professor and principal investigator at Seattle Children’s Research Institute’s Center for Immunity and Immunotherapies, and an attending physician in the Rheumatology Division at Seattle Children’s Hospital which is ranked among the nation’s best children’s hospitals by U.S. News & World Report. Her research lab works to understand what causes autoimmune diseases, and is pursuing innovative treatments for lupus, scleroderma and juvenile idiopathic arthritis.
Dr. Stevens earned her MD and a PhD in Immunology and Microbiology at the Baylor College of Medicine, completed a residency in pediatrics at Children’s Hospital Medical Center in Cincinnati, and did a fellowship in pediatric rheumatology at the University of Washington. She is board certified in pediatrics and rheumatology.