The recent successful First-in-Class (FIC) Phase III KarMMa-3 trial of ABECMA/Ide-cel versus Standard of Care (SOC) established triplets with 2-4 prior lines of treatment has the potential to bring this BCMA CAR-T therapy earlier in the paradigm with my estimate of 6 months to file an sBLA, 60 days for the FDA to accept the sBLA and 6 months review with potential launch by 4Q2023.
Phase II KarMMa-2 in 2L+ RRMM is expected to read out in 2022. In fact, it was originaly supposed to read before Phase III KarMMa-3.
On the CELMoD front, BMY has identified Iberdomide/CC-220 (IBER) as a potential Revlimid/Lenalidomide replacement and Mezigdomide/CC-92480 (MEZI) for Pomalyst/Pomalidomide. Note it is my strong recommendation to just use MEZI as GC and a KOL at EHA2022 both stumbled over the full name ;<)
During the BMY 2Q2022 earnings CC, confirmation was given that the first Phase III IBER trial EXCALIBER with an experimental arm of IBER+Dara+low dose dex (IDd) versus control Dara+Velcade+low dose dex (DVd) is underway. Look for detailed presentation at ASH2022. IBER's safety profile is quite differentiated with almost no non-hematological Grade 3 or higher serious adverse events (SAE) lending itself to broad combinations in early lines.
In 2023/2024 Key Milestones there are two important planned initiation of Phase III IBER trial in post-transplant maintenance head-to-head (H2H) versus Revlimid and Newly DiagnosedMultiple Myelom (NDMM) H2H versus Revlimid.
It does not appear that the Phase I/II dose expansion for IBER+dex for heavily pre-treated patients was sufficiently compelling to file. A large set of MEZI+dex is hopefully due at ASH2022. If replicating early data (54.5% ORR) at the Recommended Phase II Dose(RP2D), there may be the potential to file on this single arm data.
The 2023/2024 Key Milestones include initiating a Phase III triplet MEZI trial in 2L+ RRMM. Early results of MEZI+Velcade/Bortezomid+low dose dex (MZd) for subjects with median 3 lines of prior therapy looked promising.
|Msg 9265 of 10143 at 3/17/2022 5:17:13 PM by|| edit | delete|
Re: Rupert Vessey talking at Guggenheim well worth listening to, IMO - or reviewing transcript
The following message was updated on 2/6/2022 8:33:58 AM.
|Msg 8963 of 8975 at 2/5/2022 6:43:48 PM by||edit | delete|
Re: Endpoints 4Feb2022 Article "Bristol Myers' Caforio: CELMoDs have potential to replace Revlimid and Pomalyst as blockbusters start to lose exclusivity"
The Multiple Myeloma (MM) vision articulated in 2016 continues to develop. The first thread covers the early 2021 update followed by further specification in 2022.
It is worth noting that clinical trials take progressively longer pursuing earlier lines of therapy. A successful trial will by definition run longer than the control arm to be statistically significant.For example, the planned head-to-head (H2H) Iberdomide/CC-220 versus Revlimid Phase III in post-ASCT maintenance has historical control arm Progression Free Survival (PFS) of 41 months based on IFM-2005-02 or Time to Progression (TTP) of 57.3 months from CALGB-100104.
The ASCT-ineligible newly diagnosed MM (NDMM) standard of care (SOC) options are Darzalex+Rd (DRd) based on Phase III MAIA trial not yet reaching median PFS after 5 years/60 months and Velcade+Rd (VRD) 43 months from SWOG-0777. Perhaps FDA will allow MRD negativity as a surrogate endpoint to facilitate an earlier readout.
The first CELMoD Phase III is EXCALIBUR, comparing Iberdomide+Darazalex+low dose Dex (IDd) versus Darzalex+Velcade+low dose Dex (DVd) in 2L+ Relapsed/Refractory MM (RRMM) with an estimated Primary Completion Date of 17May2024. DVd showed a 16.7 mPFS in CASTOR Phase III.
|Msg 6392 of 8962 at 3/4/2021 1:37:21 PM by||edit | delete|
Re: Why We Will Have A Revlimid transition vs. A Downward "Cliff" After 2025
BMY/CELG's Multiple Myeloma (MM) sophisticated strategy for continued category dominance as Revlimid and Pomalyst go through a gradual LOE process over several years involves many different therapeutics platforms.
The original vision was articulated during CELG's Multiple Myeloma Deep Dive on 24May2018:
The JPM2021 slide reflects a more current visual of the approach:
The following slides provide the 2022 update on that vision: