BioPharma

Bristol-Myers Squibb holds lead among myeloma drugs with popular antigen target, analyst writes

A Cannacord Genuity analyst pointed to BMS’ large pipeline of BCMA-targeting therapies and advanced data, particularly for its CAR-T. However, GlaxoSmithKline has also asserted its anti-BCMA drug could be first past the FDA finish line. But does it matter?

Finish line ahead

Bristol-Myers Squibb is ahead of the pack of companies developing drugs to treat the blood cancer multiple myeloma by targeting the cell-surface protein BCMA, according to an investment bank analyst.

In a note to investors Tuesday, Cannacord Genuity analyst John Newman wrote that New York-based BMS has a “favorable lead” in the space of anti-BCMA drugs, citing the advanced development of the CAR-T therapy it’s developing with bluebird bio, idecabtagene vicleucel, as well as other drugs in its pipeline that target the same antigen. Newman examined important factors like the characteristics of patients in the various companies’ clinical trials and those trials criteria for including or excluding patients.

Top-line results from the Phase II KarMMa study showed a 73.4% overall response rate and 31.3% complete response rate, with a median 10.6-month duration of response and 8.6-month progression-free survival – numbers that went higher, including an 11.3-month median PFS, when only counting patients who received the highest dose. All patients had at least three prior therapies, and 84% were refractory to an immunomodulating drug, a proteasome inhibitor and a CD38-targeting monoclonal antibody, considered the “backbone” drug classes of myeloma.

Newman wrote that although another BCMA-targeting CAR-T, Johnson & Johnson’s JNJ-4528, also showed very high response rates, it appeared patients in the BMS-bluebird study had more prior lines of therapy and more rapid progression of their disease on their last treatment regimen. The timing of when patients were supposed to have relapsed in the respective studies indicates J&J’s trial may have included those with less aggressive disease, he wrote.

BMS has other BCMA-targeting therapies up its sleeve as well. These include bb21217, which is a specially modified form of ide-cel that it is also developing with bluebird, as well as three other CAR-Ts. Outside of CAR-T, it is developing a bispecific antibody against BCMA, CC-93269.

Competitors in the BCMA field include Amgen and Regeneron Pharmaceuticals’ bispecific antibodies, AMG 420 and REGN5458, as well as GlaxoSmithKline’s antibody-drug conjugate, GSK2857916 (belantamab mafodotin).

Newman wrote that ide-cel would likely be the first in the pack to win Food and Drug Administration approval and thus have the first-mover advantage. However, GSK has also expressed confidence that its drug could be the first anti-BCMA therapy past the finish line. The London-based company said Jan. 21 that the FDA had given priority review to its drug and is expected to reach a decision in the first half of this year. That was on the back of data showing a 12-month median PFS among patients. However, Newman pointed out that patients in GSK’s study were less heavily pretreated than those in KarMMa, receiving a median three prior lines of therapy, compared with six in KarMMa.

But another question is if it even matters whether ide-cel or belantamab mafodotin is the first to win approval, and whether the therapies would be competitive or complementary.

It is possible that rather than competing directly with CAR-Ts, off-the-shelf therapies like GSK’s drug and AMG 420 – which lack CAR-T cells’ cumbersome and expensive manufacturing and administration – would instead mainly be used in earlier lines of treatment or in patients unsuitable for CAR-T. That has been the case with another Amgen bispecific antibody, Blincyto (blinatumomab) for acute lymphoblastic leukemia, which like the approved CAR-Ts – Novartis’ Kymriah (tisagenlecleucel) and Gilead Sciences’ Yescarta (axicabtagene ciloleucel) – works by targeting the antigen CD19. But only a small minority of patients receiving Blincyto have relapsed with CD19-negative disease, and many patients receiving the CAR-Ts are previously treated with Blincyto.

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