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Bristol cuts its BCMA losses

Meanwhile, the RayzeBio-originated RYZ101 is back in Action.

When Bristol Myers Squibb began the phase 3 trial of its BCMA-targeting T-cell-engager alnuctamab in February, there were questions about how the project might compete in a crowded market. The answer appears to be that it can’t, with Bristol slipping out the discontinuation of the asset during its second-quarter earnings on Friday.

The company didn’t give a reason but the multiple myeloma study in question, Alumminate, was withdrawn in May, with its clinicaltrials.gov listing noting that “business objectives have changed”. Bristol is already losing one BCMA battle against Johnson & Johnson in the Car-T space; perhaps it didn't relish the prospect of another.

When asked by ApexOnco about the discontinuation, a spokesperson for Bristol cited the "evolving landscape" in multiple myeloma. Since the study began, Car-T therapies from J&J and Bristol have got the go ahead for earlier lines of disease. These decisions were anticipated, though, so perhaps the real question is why Bristol began Alumminate in the first place. However, it should be noted that the latest move comes against a backdrop of broader cost cuts at the company.

J&J battle

J&J is the company to beat in BCMA, with an approved Car-T, Carvykti, and bispecific, Tecvayli.

In Car-T, J&J is clearly on top: in the second quarter, Carvykti revenues grew 60% to $186m, perhaps helped by the recent approval in second-line disease. Meanwhile, sales of Bristol and 2seventy bio’s rival product Abecma shrank 28% to $95m during the same period, despite its new third-line label. Bristol clung to a quarter-on-quarter rise, and ex-US growth, but Abecma is still looking like an also-ran.

In bispecifics, it’s harder to call: here J&J, which only recently began reporting Tecvayli sales, is being challenged by Pfizer with Elrexfio; that product was approved last August in the same fifth-line setting, and Pfizer is yet to split out revenues.

Another BCMA bispecific could soon hit the market, with Regeneron’s linvoseltamab due an FDA approval decision due by 22 August for fourth-line multiple myeloma. On one hand, Bristol’s withdrawal could be seen as good news for Regeneron, as it eliminates a competitor; however, it could be seen as bad if it signals a lack of opportunity for newcomers.

The other BCMA bispecific in late-stage development is AbbVie’s TeneoOne-derived ABBV-383, which recently started the Cervino phase 3 study in third-line disease.

Bristol hasn’t got out of BCMA research entirely: it also has a dual targeting BCMA x GPRC5D Car-T, BMS-986453, in phase 1, as well as a straight GPRC5D-targeting Car-T, BMS-986393, in the mid-stage Quintessential study. The group's other efforts in multiple myeloma include the “celmods” iberdomide and mezigdomide, in phase 3 with data coming in 2026.

RYZ101 resumes

Bristol’s latest cost cuts come not long after some big acquisitions, and there was good news for one of these last week. The Action-1 trial of the SSTR2-targeting radiopharmaceutical RYZ101 – gained via the $4.1bn purchase of RayzeBio – has resumed, the company said during its earnings call. The study, in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) previously treated with Novartis's Lutathera, was paused in June because of shortages of actinium-225, the alpha emitter used as a payload in RYZ101.

Bristol added that results from that study are due in 2026; they had previously been expected in 2025.

The company admitted that GEP-NETs will be a "fairly modest" commercial opportunity, but pointed to an ongoing phase 1 study in small cell lung cancer, and potential in other tumour types.