Lupus drug moves forward

SEATTLE—A sea anemone-derived compound with the potential to treat a diverse range of autoimmune diseases has produced positive results in a study of patients with lupus nephritis. The findings of an ex-vivo study using dalazatide in children and teens with lupus nephritis suggest that the drug has the ability to suppress cytokines that are associated with disease inflammation to a degree similar to current therapies that have severe side effects. Dalazatide is a synthetic analog of a peptide isolated from a Caribbean sea anemone that is being developed jointly by biotech firms Kineta and KPI Therapeutics.

Kineta and KPI claim that dalazatide is the first Kv1.3 potassium channel blocker to ever achieve successful clinical trials. Inhibition of the Kv1.3 channels on effector memory T cells has become an important strategy for the treatment of autoimmune disorders. Effector memory T cells are a subset of the T cell family that cause inflammation and tissue damage in a broad range of autoimmune diseases. Dalazatide blocks activation of these cells without suppressing other T cell subtypes, potentially leaving intact the innate immune response and a majority of the adaptive immune response. The result is that dalazatide may not cause broad immune suppression in patients like many current treatments for autoimmune diseases.

“By only targeting these effector memory T cells, dalazatide can inhibit some of the autoimmune disease while leaving the rest of the immune system intact and able to fight infections and battle cancers,” Chelsea Olsen, director of Alliance Management at KPI, tells DDNews. “That’s different than a lot of the other autoimmune disease drugs that are currently available, which are broadly T cell-suppressant and that leave patients susceptible to infections.”

Olsen says the lupus study comes after many years of active research into the potential of Kz1.3 pottasium channel blockers. Some previous attempts to move compounds into clinical development have failed, she says, because the drugs being tested targeted too broadly and caused off-target effects.

“People have seen the value for a long time and come to view this as a really an exciting target with a lot of potential,” she says. “But we’re the first to get a drug into clinical development.”

Kineta and KPI view dalazatide as having potential to treat a range of diseases including multiple sclerosis, Krohn’s disease, inflammatory bowel disease, type 1 diabetes and lupus nephritis. Dalazatide has also completed a Phase 1B clinical trial in plaque psoriasis.

“We’re especially focused on pushing forward development of dalazatide in areas where there are currently not a lot of options,” Olsen tells DDNews.

The dalazatide study in lupus patients was spearheaded by a coalition called the Alliance for Children’s Therapeutics that includes Kineta, the Seattle Children’s Research Institute and KPI Therapeutics. The results of the study were presented at the European League Against Rheumatism’s 17^th Annual Congress in London. Anne Stevens, a researcher at the Seattle Children’s Research Institute and leader of the study, presented the work at the congress.

“New study data shows that patients with active lupus nephritis express higher levels of the Kv 1.3 channel, the target of dalazatide, than do patients with inactive disease or healthy volunteers,” Stevens said. “T cells from patients with active lupus are sensitive to blockade by dalazatide, demonstrating ex-vivo efficacy of the drug, and provide data to support the design of a clinical trial in patients with lupus.”

The new data show that dalazatide can decrease a group of cytokines functioning as biomarkers associated with active lupus disease. Researchers say this ability of the drug gives it the potential to treat disease inflammation as effectively as more toxic treatments like cyclosporine A without the adverse effects that often are associated with their toxicity.

“There is a real need for more effective therapies to treat lupus disease and many other autoimmune diseases,” Olsen tells DDNews. “Lupus is a complex disease and the treatments that are out there are not specific and not very effective.”

Lupus nephritis is an autoimmune disease which causes kidney inflammation and damage. Current medications are effective in reducing some of the inflammation associated with the disease, but they also suppress normal functions of the immune system, an undesirable side effect that is particularly problematic in children.