Game on: Regeneron's BCMA bispecific makes clinical data debut, kicking off multiple myeloma matchup with Bristol-Myers
As J&J attempts to jostle past Bristol-Myers Squibb and bluebird for a landmark approval of its anti-BCMA CAR-T — and while GlaxoSmithKline maps a quick path to the FDA riding on its own BCMA-targeting antibody-drug conjugates — the bispecifics are arriving on the scene to stake a claim for a market that could cross $10 billion per year.
The main rivalry in multiple myeloma is shaping up to be one between Regeneron and Bristol-Myers, which picked up a bispecific antibody to BCMA through its recently closed $74 billion takeover of Celgene. Both presented promising first-in-human data at the ASH 2019 meeting.
“Although Celgene has both a time and myeloma experience advantage, we believe Regeneron is close behind and could even catch up if the megamerger leads to some program delays” was Baird analyst Brian Skorney’s take as he scored the first myeloma data for REGN5458.
With bispecifics the general idea is to bridge T cells and tumors cells, thereby inducing the killing of cancer. REGN5458, in particular, binds to the CD3 receptor on the immune cells and BCMA on multiple myeloma cells.
Investigators had data on the first two dose groups to report from the ongoing Phase I/II dose escalation study, in which 3 patients were given 3mg weekly doses and 4 patients received 6mg. Overall, 4 of them recorded a response — giving rise to a 57% response rate overall — 3 of them from the 6mg group (75% response rate there). Among those three taking the higher dose, two passed the crucial test of being minimal residual disease (MRD) negative, a high bar suggesting no cancer cells were detectable in their bone marrow.
Notably, these patients have had a median of seven lines of prior therapy and had all failed CD38 antibody treatment. And at the 6mg dose level, the median number of prior treatment was even higher at 9.5, Skorney noted.
Cytokine release syndrome, anemia and lymphopenia were all documented, though Regeneron said the adverse events were not dose limiting.
Their results come on the heels of Bristol-Myers/Celgene’s data reveal, in which CC-93269 showed an 89% response rate in the highest dose of 10mg after being investigators went up from 0.15mg with 30 patients total.
“CC-93269 shows promising dose-dependent efficacy, including MRD-negative sCRs, with a convenient administration schedule in patients with heavily pretreated relapsed/refractory multiple myeloma.”
Most of the grade 3 or higher adverse events were neutropenia, anemia and infections, the investigators noted, though cytokine release syndrome also cropped up in 76% of all patients in the trial.
In the Regeneron trial, three patients experienced CRS, amounting to a 42% occurrence.
“We are encouraged to see promising, rapid clinical activity even at the initial two doses of REGN5458 in heavily pretreated patients with multiple myeloma,” Israel Lowy, head of clinical and translational sciences for oncology at Regeneron, said in a statement. “We are actively recruiting patients into higher dose groups in this trial and look forward to sharing further results in 2020.”
Lowy added that the Tarrytown, NY-based biotech has initiated a trial for its second BCMA/CD3 bispecific, which binds differently. They are moving fast — and they need to in a field brimming with competitors.
Pfizer is advancing its own version, although the absence of equivalently promising data at ASH pushed Skorney to surmise “not all bispecifics are created equally.” AbbVie also got its hands on a bispecific hooking to the same targets from a $90 million deal with Teneobio.
CC-93269 had a 89% ORR, 33% CR at 10 mg doses. This can be combined with bortezomib and lenalidomide to keep pressure on the tumor in perpetuity. If you can’t cure myeloma, which I don’t see evidence for, you will need to keep pressure up. Not feasible with CART
— Brian Skorney (@BrianSkorney) December 7, 2019