Top Line: SB3 (aka Ontruzant) is a trastuzumab biosimilar that turned the Herceptin market on its head with FDA approval in early 2019 after its similarity simply couldn’t be denied on several large prospective trials.
The Study: A secondary analysis of one of these more publicized trials, SB3-G31-BC, is here to demonstrate, if there’s anything dissimilar about SB3, it’s in the superior direction. Eyebrows were slightly raised when the confidence interval for the primary endpoint of complete path response actually surpassed the upper boundary of prespecified equivalency with SB3 (52%) versus trastuzumab (42%) when added to neoadjuvant chemo in the initial reporting. Believe it or not, this was chalked up to a slight manufacturing error in trastuzumab during the period of the study that resulted in less potent antibody-dependent cell-mediated cytotoxic effects, referred to in pharm speak as ADCC downward drift. Well, the secondary analysis confirms this translated to a numeric, if not statistically significant, advantage at 5 years in both event-free (80% v 75%, respectively) and overall (93% v 85%) survival. Remarkably, on subset analysis a difference in outcomes was, in fact, concentrated in the 60% of women on the trastuzumab arm who received the slightly defunct product—their hazard ratio for experiencing recurrence or death was 2.57 that of women receiving non-defunct trastuzumab. On the other hand, outcomes were much more closely aligned between the SB3 arm and the 40% of women on the trastuzumab arm receiving a non-defunct product. Finally, cardiac events were almost nonexistent with only 3 of 367 enrollees experiencing asymptomatic significant LVEF decreases, likely due to intensive cardiac monitoring on treatment with early stopping rules.
TBL:SB3 appears equally (very) safe and effective as appropriately manufactured trastuzumab, and it’s never a bad idea in terms of economics and quality assurance to have multiple producers of any critical pharmaceutical product. | Pivot, JAMA Netw Open 2023
The Study: A secondary analysis of one of these more publicized trials, SB3-G31-BC, is here to demonstrate, if there’s anything dissimilar about SB3, it’s in the superior direction. Eyebrows were slightly raised when the confidence interval for the primary endpoint of complete path response actually surpassed the upper boundary of prespecified equivalency with SB3 (52%) versus trastuzumab (42%) when added to neoadjuvant chemo in the initial reporting. Believe it or not, this was chalked up to a slight manufacturing error in trastuzumab during the period of the study that resulted in less potent antibody-dependent cell-mediated cytotoxic effects, referred to in pharm speak as ADCC downward drift. Well, the secondary analysis confirms this translated to a numeric, if not statistically significant, advantage at 5 years in both event-free (80% v 75%, respectively) and overall (93% v 85%) survival. Remarkably, on subset analysis a difference in outcomes was, in fact, concentrated in the 60% of women on the trastuzumab arm who received the slightly defunct product—their hazard ratio for experiencing recurrence or death was 2.57 that of women receiving non-defunct trastuzumab. On the other hand, outcomes were much more closely aligned between the SB3 arm and the 40% of women on the trastuzumab arm receiving a non-defunct product. Finally, cardiac events were almost nonexistent with only 3 of 367 enrollees experiencing asymptomatic significant LVEF decreases, likely due to intensive cardiac monitoring on treatment with early stopping rules.
TBL:SB3 appears equally (very) safe and effective as appropriately manufactured trastuzumab, and it’s never a bad idea in terms of economics and quality assurance to have multiple producers of any critical pharmaceutical product. | Pivot, JAMA Netw Open 2023