The primary endpoint was the complete remission/complete remission with partial haematological recovery (CR/CRh*) rate within 2 cycles of treatment with BLINCYTO. Eighty-one of 189 (%) patients achieved CR/CRh* within the first 2 treatment cycles with the majority of responses (64 of 81) occurring within 1 cycle of treatment. In the elderly population (≥ 65 years of age) 11 of 25 patients (%) achieved CR/CRh* within the first 2 treatment cycles (see section for safety in elderly). Four patients achieved CR during consolidation cycles, resulting in a cumulative CR rate of % (67/189; 95% CI: % - %). Thirty-two of 189 (17%) patients underwent allogeneic HSCT in CR/CRh* induced with BLINCYTO (see table 1).
The histidine and aspartate side-chains are used to effectively stabilize the substrate within the active site and also participate in deprotonation of the substrate. To be specific, the His 263 and His30 side-chains form hydrogen bonds to the aldehyde end of the substrate, which is deepest into the substrate channel, and Asp477 forms hydrogen bonds with the alpha hydroxyl group on the substrate, where it works to effectively bind the substrate and check for proper stereochemistry. It is also thought that Asp477 could have important catalytic effects because of its orientation in the middle of the active site and its interactions with the alpha hydroxyl group of the substrate. Glu418, which is located in the deepest region of the active site, plays a critical role in stabilizing the TPP cofactor. To be specific, it is involved in the cofactor-assisted proton abstraction from the substrate molecule.