Dupilumab

Connect Biopharma’s hopes of dethroning Dupixent took a knock as its IL-4/IL-13 blocker missed the primary endpoint of a phase 2 asthma study. The mid-stage trial enrolled 160 patients with asthma and type 2 inflammation who received either Connect's rademikibart subcutaneously or placebo. Rademikibart was able to reduce the rate of treatment failure by 66% over 28 days compared to placebo. However, this was not enough to demonstrate statistical significance, which Connect blamed on an “overall lower treatment failure rate than projected.” Searching for a silver lining, Connect pointed to a statistically significant increase from baseline in the secondary endpoint of post-bronchodilator forced expiratory volume in one second (FEV1), a breathing test to check the amount of air you can forcefully blow out of your lungs in the first second of a deep breath. The topline failure comes in the wake of a phase 3 win in China for rademikibart in patients with atopic dermatitis, which was reported by Connect's partner Simcere Pharmaceutical back in March. San Diego-based Connect is now awaiting topline data from another phase 2 study of rademikibart in patients with chronic obstructive pulmonary disease (COPD), which is expected at the end of the month. Despite the miss, Connect CEO Barry Quart insisted in the release that the topline data this morning “supports [rademikibart's] potential to meaningfully improve outcomes for patients in the critical period after an exacerbation.” “The overall results of this study provide a clear roadmap for design of a phase 3 program,” the CEO added. Investors didn't seem reassured, sending Connect's stock down 35% to $1.12 in the first hour of trading Tuesday from a Monday closing price of $1.73. On a call this morning to parse through the latest data, analysts voiced their concerns about the overlap in study site and enrollment of today's asthma trial and the ongoing COPD trial, and what that might mean for the next readout. CEO Quart explained that although there is a “great deal of overlap” in the studies, they are not seeing the level of events of treatment failure that his team observed in the asthma study. The company is also considering how to evaluate administering rademikibart intravenously, Quart said. “We believe that the IV dose has the opportunity of much faster onset … a really ideal profile for use in the emergency department,” the CEO added. “We're also looking at the option of potentially developing both IV and subcutaneous for the acute population.” Rademikibart is an anti-interleukin-4-receptor alpha (IL-4Rα) antibody that prevents the receptor from interacting with other receptor subunits that are required for activation of the signaling pathways that lead to asthma. Simcere paid $21 million upfront for the China rights to the drug, amid hopes the therapy could rival Sanofi and Regeneron's blockbuster asthma and COPD drug Dupixent.