During the conference call, the analysts asked many questions about the FOCUS study. It was clear from the tone of the questions that they were raising some doubts about the outcome of the study. I believe, the analysts' emphasis on the FOCUS study was typically misplaced. The ASPIRE study is much more important. We already know that as a single agent, Kyprolis has modest efficacy in the relapsed population. What is more important is whether the Kyprolis-Revlimid combination is going to show significant synergistic effects and strong efficacy. So far, several the studies point to truly exceptional efficacy in the combination carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) for newly diagnosed multiple myeloma (NDMM). For example, Jakubowiak et al reported that: With extended tx, the CR rate was 64%; sCR improved from 42% to 53%, ≥nCR from 62% to 72%, and ≥VGPR from 81% to 87% (follow-up 13 vs 25 mo); ≥PR remained at 98%. Immunophenotypic CR (IMWG) was achieved in 22/26 evaluated pts. Of pts in sCR, 25% had high-risk cytogenetics per IMWG. In pts who did not proceed to transplant (n=46), the sCR was 59%, CR 70%, ≥nCR 78%, ≥VGPR 91%, and ≥PR 100%. Over the course of tx, depth of response improved. Median time to ≥VGPR was 4 cycles (range 2–17), ≥nCR 4.5 cycles (range 2–15), and sCR 10 cycles (range 4–30); 2 pts converted to sCR during LEN maintenance. At 2 years, the estimated PFS rate was 94% and OS was 98%; for pts with sCR, rates were 96%.
I don't believe there are any serious doubts about the outcome of the ASPIRE study. If the above exceptional efficacy is confirmed by the larger studies, then the CRd combination will most likely become the dominant front-line treatment with profound implications for Kyprolis sales.