Beyond the Headlines: Dr. Jonathan Silverberg Reviews Maintenance Data on Rademikibart From a Pivotal Trial in China

Connect Biopharma’s rademikibart showed a maintenance of response that “more than doubles” other AD drugs.

DermWire recently reported positive topline results from a 52-week maintenance study of rademikibart in people with atopic dermatitis (AD).  At 52 weeks, rademikibart, an interleukin-4 receptor alpha (IL-4Rα)-inhibitor, demonstrated consistent safety and sustained efficacy across all key endpoints with both every two-week and every four-week dosing schedules compared to other biologics. 

Here, study author Jonathan Silverberg MD, PhD, Associate Professor of Dermatology Director of Clinical Research and Contact Dermatitis at The George Washington University School of Medicine and Health Sciences in Washington, DC, unpacks the results and their implications.

How does rademikibart differentiate from what is out there already? 

Jonathan Silverberg MD, PhD: “For the first 16 weeks of the study, the efficacy looked good, but it was somewhat similar to the level of efficacy that we see with dupilumab, for example, with every two-week dosing.  The new 52-week data, which is the maintenance phase of the company’s China pivotal trial, shows maintenance of response with Investigator Global Assessment (IGA) Clear and Eczema Area and Severity Index (EASI-75). Of patients who had achieved an EASI-75 score or an Investigator's Global Assessment (IGA) score of 0 or 1 at week 16, 76% to 87% maintained their IGA score of 0 or 1 by week 52, and 92% maintained EASI-75 by the same endpoint.  These are the best numbers we have seen by more than double. Those patients who didn’t respond at week 16 did achieve a response over time.  From the data we have seen so far, this drug has the potential to be best in class.”

What about every four-week dosing?

Dr. Silverberg: “With every four-week dosing, we also are seeing the best numbers we have seen in terms of maintenance of response. When dropping from every two weeks to four weeks, we continued to gain response even with more spread-out dosing.  We are not just maintaining response but gaining response over time. If it works this well every four weeks, could less frequent dosing also produce a clinical response? We don’t know yet.”

What’s the status of rademikibart in the US?

Dr. Silverberg: “Connect Biopharma is waiting for a partner to take it forward in the US. These new topline results will inform regulatory approval in China and continue to build the body of evidence supporting the efficacy and safety of this drug.”

What’s the bigger picture with AD treatment?

Dr. Silverberg: “We saw the development of multiple drugs in psoriasis, and with each new generation of medicines that came, we saw gains in both efficacy safety and dosing and now we have got some amazingly effective medications in psoriasis.  AD is not psoriasis. In AD, we are seeing a lot of innovation and a lot of additions to our toolbox, and each drug makes an important contribution but none fixes everything… yet.  In five to 10 years, Th2-blocking biologics will continue to be the treatment of choice in AD, and there will be a bunch of different ones to choose from. Many clinicians will cycle through biologics through trial and error like we did with TNF inhibitors in psoriasis in the early days. There will be Something for everybody but no single magic bullet that will be the perfect medication for every AD patient.”