Abstract Background and aims Alteplase and tenecteplase are widely used to lyse the clot in patients with acute cerebral ischemic stroke (ACIS). Sovateltide (Tycamzzi®), a novel endothelin B receptor agonist, is being marketed in India and is undergoing phase 3 clinical trials (RESPECT-ETB) in the USA, Germany, Spain, Australia, and the UK for the treatment of ACIS. We evaluated whether sovateltide affected the thrombolytic activity of alteplase and tenecteplase. Methods The clot-lysis potential of sovateltide, alteplase, and tenecteplase, and the effect of sovateltide on the clot-lysis potential of alteplase or tenecteplase, was studied using the microtiter plate clot-lysis assay at multiple time points. Calcium chloride (1563 mM) was used to produce microclots of human citrated plasma. A buffer concentration of 0.0 μg/mL was tested for spontaneous clot lysis, and absorbance values were recorded at 405 nm using a microplate reader at '0' minutes. The data is expressed in percentages of clot mass and lysis. Results No lysis of the clot was observed with sovateltide (concentration range of 5 to 80 μg/mL). The thrombolysis activity of alteplase or tenecteplase, alone and in combination with sovateltide, was comparable. Sovateltide did not alter the clot-lysis activity of alteplase (1.25 μg/mL) or tenecteplase (5.0 μg/mL) when administered in combination. Alteplase and tenecteplase retain consistent potency when combined with sovateltide (200 μg/mL). Conclusions Alteplase and tenecteplase exhibited thrombolysis activity in a concentration and time-dependent manner. Sovateltide alone did not exhibit any clot-lysis activity, and it did not influence the clot-lysis potential of alteplase or tenecteplase. Conflict of interest Anil Gulati, Manish Lavhale, Dharmesh Shah and Amaresh Ranjan are employees and stockholder of Pharmazz Inc.
Lavhale et al. (Fri,) studied this question.