ASH 2025 – BeOne pulls away from Nurix
On efficacy, at least, BeOne’s BTK degrader shows an edge.
On efficacy, at least, BeOne’s BTK degrader shows an edge.
The battle between BeOne and Nurix’s BTK degraders has rumbled on for a couple of years, with both showing near-equivalent activity in chronic lymphoblastic leukaemia – until now. During adjacent ASH presentations on Saturday BeOne’s BGB-16673 put up efficacy data that appeared to give it the slightest of edges over Nurix’s bexobrutideg.
As it stands, BeOne is taking forward a 200mg BGB-16673 dose, which produced a 94% best response rate; the best Nurix can boast of is an 83% response rate, and that came with a higher, 600mg, bexobrutideg dose that it says looks optimal. Still, cross-trial comparisons are inexact, and for its part Nurix might be able to argue that bexobrutideg has a safety advantage.
Both the studies presented involved 50-600mg doses, and the headline response rate numbers amounted to 85% for BGB-16673 among 68 patients, and 81% for bexobrutideg among 84. So far so similar, but BeOne said it had selected 200mg as the dose for expansion, and it’s here that a difference emerges.
BeOne split out BGB-16673’s activity by dose, and highlighted the 94% response rate among 18 patients on 200mg, backing its decision to focus on this dose. Of course, this could be an artefact of small patient numbers; all 12 patients given 500mg responded, but the rate among 15 given 350mg was only 73%, for instance.
For its part Nurix’s data related to 47 patients across the 50-600mg part 1a of bexobrutideg’s trial, and 37 given 200mg or 600mg in part 1b. The latter part has so far yielded an 83% response rate for the 600mg dose; with 200mg appearing worse (74% best response rate), Nurix said it was moving ahead with 600mg in phase 2.
Cross-trial comparison of BTK degraders in CLL
| BGB-16673 (BeOne) | Bexobrutideg (Nurix) | |
|---|---|---|
| Study | Cadance-101 | NX-5948-301 |
| Efficacy-evaluable n | 68 (50-500mg doses) | 84 (50-600mg doses) |
| Pts with prior covalent BTKi | 94% | 86% |
| Pts with prior non-covalent BTKi | 21% | 27% |
| Discontinuations owing to TEAE | 3 | 8 |
| Atrial fibrillation | 3 | 1 |
| Infections | 5 deaths, mostly due to infections, none treatment-related; 1 pt discontinued owing to gr3 aspergillosis, not treatment-related | No systemic fungal infections, no gr4 infections of any kind |
| Best response rate | 85% | 81% |
| Best response rate 200mg | 94% (n=18) | 74% (n=19) |
| Best response rate 600mg | NA | 83% (n=18) |
| 12mth PFS | 74% | 62%* |
| 18mth PFS | 66% | 54%* |
Note: *part 1a (50-600mg) only. Source: ASH.
On the face of it, safety appeared comparable between the two molecules, including similar rates of treatment-emergent deaths, none of which were deemed by investigators to be treatment related.
However, two possible areas of differentiation are emerging. The first is atrial fibrillation, which was seen in just one bexobrutideg patient, but in three of those in the BeOne study. The presenter, Dana-Farber’s Dr Inhye Ahn, said the three events were all graded 1 or 2, and were all transient, but said there were also two grade 3 major haemorrhages, and these were deemed related to BGB-16673.
Secondly, controversy arose around infections, with five patient deaths in the BeOne trial being described as “mostly due to infections” but not treatment related. One patient discontinued BGB-16673 owing to grade 3 aspergillosis, but this too wasn’t deemed treatment related.
During a question-and-answer session the decision not to grade these as treatment related was raised. As if to drive the point home, Nurix stated that its bexobrutideg study showed “no systemic fungal infections, or grade 4 infections of any kind”.
Development of both molecules continues, with BGB-16673 in the pivotal Cadance-302 and 304 studies, and Nurix planning to take bexobrutideg into the phase 3 Daybreak CLL-306 trial. Mizuho analysts, who cover Nurix, suggested that the projects’ safety was “looking more and more to be a point of differentiation”.
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