These preliminary results reported in Kyoto in April 2013 are very encouraging--it looks like that in the head-to-head trial, Kyprolis is likely to show better efficacy in addition to the substantially lower neuropathy. Expansion of Kyprolis' label to frontline treatment is only a matter of time and the price should start reflecting that prospect.
Preliminary results of Kyprolis/melphalan/prednisone look promising. Of the published abstracts, we highlight the Phase I/II trial evaluating melphalan/prednisone/carfilzomib (Kyprolis), or MPC, in newly diagnosed multiple myeloma (NDMM) patients under 65 years old. As of the cutoff date of January 6, 2013, 24 patients were enrolled in Phase II and 45 patients in the Phase II portion of the trial (n=69). Overall response rate (ORR) was 89%, with 51% achieving greater than VGPR (very good partial response). This compares to an ORR of 74% (with 33% achieving VGPR) based on the International Uniform Response Criteria in the Phase III VISTA trial evaluating melphalan/prednisone/Velcade (MPV) in NDMM. These results bode well for the outcome of Onyx’s Phase III CLARION head-to-head trial, which will also be evaluating MPC vs. MPV. This front-line trial was just initiated in March 2013, with an estimated primary completion date in April 2016 (source: clinicaltrials.gov).
Good find, John! Now I just wonder, if based upon these results, will oncologist start using Kypro as first line, without waiting for any additional results (that looks like to me can come by the end '14, the earliest).
Also, judging by recent success of MRK, BMY etc in some combination therapies, what would be the most promising combination to try Kypro with?
Someday I will learn to stop spelling Kyprolis as "Kyrpolis". We should note that although the FDA-approved "on label" usage of Kyprolis is for those who are refractory to the conventional Velcade regime, the NCCN (National Comprehensive Cancer Network) guidelines were changed back in March to allow the use of the Kyprolis/Revlimid/dexamethasone combo as a frontline treatment. I have seen anecdotal evidence that oncologists at Mayo and elsewhere are adopting this. The large study still underway at NIH in Bethesda under Dr. Jubowiak (sp?) has been using this combo on newly diagnosed patients for a long time with great success. In short, I don't think we need to wait until definitive evidence of Kyprolis's superiority to Velcade is in to see Kyprolis widely adopted as a frontline treatment. Oncologists are not particularly troubled, I think, by using drugs off-label.
It is very important to note that the CMP results to be reported by Moreau et al at the European Hematology Association next week for patients 65 yr old are consistent with the results that have been presented by Jakubowiak at Kyoto for patients under 65 yr--the ORR and VGPR are exactly the same. It appears that the Kyprolis comb is superior to all other combos (not just Velcade).
CMP—CARFILZOMIB (CFZ) PLUS MELPHALAN-PREDNISONE (MP)—IN ELDERLY PATIENTS (PTS) WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): RESULTS OF A PHASE (PH) I/II TRIAL
Philippe Moreau et al Results: As of February 26, 2013, 24 pts have been enrolled in PhI: 6 for each dose level. There were 2 DLTs at 45mg/m2 (fever, hypotension) resulting in a MTD of 36mg/m². In PhII, 45 additional pts received CMP at 36mg/m² CFZ for N=69 total PhI/II pts (median age 74y). ORR was 89% with 51% ≥VGPR. With median follow-up of 12 mo, the projected 2y OS was 89.9%. CMP was well tolerated without PN ≥G2. These results compare favorably to those of MPV, MPT, MP+lenalidomide (R), and R+dex in similar pts (ORR 71% San Miguel NEnglJMed2008, 76% Facon Lancet2007, 80% Palumbo JClinOncol2007 and 85% Rajkumar LancetOncol2010, respectively). Summary / Conclusion: CFZ 36mg/m2 +MP is tolerable and effective in elderly NDMM pts. Treatment is ongoing. Final safety and efficacy data
. . . should probably be evaluating Kyprolis vs. Revlemid -- which, I think is only a few months away from likely submission to both FDA and European Union for front-line use . . . Celgene -- and most analysts, I think --already has this expected label expansion figured into its future earnings projections . . . time will tell . . .