Current biological approaches for Th2 respiratory disease, and in particular, severe asthma, target individual cytokines or their receptors. While these effectively reduce exacerbations and improve lung function and QoL across a broad population of patients, clinical remission rates in asthma remain <40%. Some tertiary centres are informally exploring combination therapies or switching between biologics to control refractory cases.
Enter bispecific antibodies – the potential game changers in severe asthma which work by hitting the inflammatory cascade in two spots at once. Several manufacturers are now developing such antibodies, including, but not limited to: Sanofi (lunsekimig; anti-IL-13/ TSLP mAb), Innovent Bio (IBI3002; anti-IL-4Rα/ TSLP), Johnson & Johnson (PX128; anti-IL-13/ TSLP mAb) and RegeneCore Biotech (RC1416; anti-IL-4Rα/ IL-5). These antibodies target a combination of cytokines that promote Th2 cell responses and allergic inflammation (IL-4, IL-13, TSLP), with RC1416 additionally inhibiting eosinophil regulation (IL-5). It is theorized that due to their mechanisms, these antibodies could more greatly benefit disease modification effects and lead to higher reductions in key inflammatory biomarkers than current approaches.
Sanofi’s lunsekimig has already shown promising Ph1b data, supporting the potential for a best-in-class profile in airway disease. Its rapid fractional exhaled nitric oxide reductions and rapid lung function improvements total an amount greater than the sum of those demonstrated in anti-TSLP and anti-IL-13 monovalent antibody studies.
So, is this really the breath of fresh air we’ve been waiting for in Th2 respiratory disease? While efficacy data points in that direction, the complete safety profile and the delicate balance of risks and benefits from these multifaceted approaches remain to be fully elucidated before the ideal patient cohort can be identified. By targeting multiple points in the inflammatory cascade simultaneously, these therapies could dramatically elevate the efficacy standard, reverse long-term disease modifications, and make clinical remission a realistic and achievable goal.
Authored by Bryson Ritson, Solici