Intermittent move beyond Blincyto
How new bispecifics at ASH are improving on dosing, toxicity short comings of Blincyto
A swath of data at ASH shows that companies have been able to move beyond the 28-day continuous dosing of Amgen Inc.’s first-generation BiTE, Blincyto, to build next-generation antibodies with more convenient, intermittent dosing and a better safety profile.
Companies expect that these advantages, and the modality’s relative lack of logistical baggage, will position the products to compete with CAR T cells as well.
Multispecific antibodies represented the third largest class of clinical cancer modality abstracts presented at the American Society of Hematology (ASH) meeting in San Diego, with several studies building on the first-generation bispecific T cell engager (BiTE), Blincyto blinatumomab (see “Cell Therapy Momentum at ASH”).
While Blincyto, which targets CD19 and CD3, showed impressive efficacy, its commercial success has been hobbled by the need for continuous dosing and a black box warning for cytokine release syndrome (CRS) and neurotoxicity.
“This has been a significant impediment and makes it hard to do the basic logistics of delivering clinical care,” said Bassil Dahiyat, president and CEO of Xencor Inc.
The challenges are due to Blincyto’s structure, which lacks key domains that confer the stability and half-life of mAbs. As a result, companies have spent the last few years tinkering with ways to make the next generation of immune cell-engaging bispecifics more mAb-like.
Four of the companies with data at ASH have engineered human mAbs with two different antigen-targeting domains and showed that these new structures could overcome Blincyto’s shortcomings. When combined with a stepped dosing regimen, these antibodies offer weekly dosing or better, and in some cases, reduced toxicity.
Efficacy comparisons are limited because the compounds were tested in different indications or subgroups of patients, and none was tested in the same indication for which Blincyto is approved.
However, Roche’s mosunetuzumab stood out on safety and convenience, with a competitive response rate from a 21-day treatment cycle, and CRS rates not exceeding grade 3 (see “Table: Bispecific Data at ASH”).
Table: Bispecific data at ASH
Data presented at the American Society for Hematology (ASH) meeting show that at least five companies have figured out how build next-generation antibodies that avoid the continuous dosing of the first-generation BiTE, Blincyto blinatumomab from Amgen Inc. (NASDAQ:AMGN). Eight companies presented data from 10 different multispecific immune cell antibody programs at ASH, and six of the programs use next-generation technology to provide intermittent dosing, with four reducing