Bristol Myers' Zenbexus win leaves shares lower

Bristol Myers Squibb's iberdomide (Zenbexus), which received FDA accelerated approval in August for relapsed or refractory multiple myeloma, now has confirmatory phase 3 data. Since mid-August, the company and its partners have reported positive late-stage readouts across blood cancer, lung cancer and neuroendocrine tumours, but the share price reactions have been uneven.

August to October: the trial readouts

On 19 August, Endpoints News reported that Chinese biotech Biokin said its EGFRxHER3 bispecific antibody-drug conjugate passed a late-stage China trial in a genetically-defined form of lung cancer. Endpoints News described the result as the fourth cancer trial the bispecific ADC had cleared, this time in non-small cell lung cancer.

On 8 October, Bristol Myers Squibb announced top-line results from the phase 3 EXCALIBER-RRMM trial in relapsed or refractory multiple myeloma. The study enrolled 800 patients, with 400 assigned to iberdomide (Zenbexus) plus daratumumab and dexamethasone (ZDd) and 400 to daratumumab, bortezomib and dexamethasone (DVd). After a median follow-up of 23 months, median progression-free survival was 42 months for ZDd versus 20 months for DVd. Bristol Myers Squibb reported a hazard ratio of 0.49, p<0.000001, and said that meant the risk of progression or death was 51% lower with the ZDd regimen. The safety profile was consistent with earlier findings. Chief Medical Officer Cristian Massacesi said the results "reinforce the clinical value of ZENBEXUS in combination with daratumumab and dexamethasone as a treatment approach for relapsed or refractory multiple myeloma". Bristol Myers said full data will be presented at the American Society of Hematology annual meeting. Benzinga noted that Bristol Myers shares were trading down 1.41% at $58.86 when the article appeared on Thursday.

Bristol Myers announced phase 3 ACTION-1 results for RYZ101, an actinium-225 DOTATATE radiopharmaceutical, in somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours that had progressed after lutetium-177-based therapy. Participants in the control arm received an investigator-chosen standard therapy, which could be somatostatin analogues, everolimus or sunitinib, while the experimental arm received RYZ101. At the planned interim look, the primary endpoint of progression-free survival was met by blinded independent central review; Bristol Myers described the benefit as statistically significant and clinically meaningful but did not give the effect size. Because overall survival follow-up is still ongoing, the data do not yet show whether RYZ101 extends life. RYZ101 is the lead programme of RayzeBio, a company Bristol Myers acquired for about $4.1bn in February 2024. The US Food and Drug Administration granted the drug orphan designation for GEP-NETs in August 2026. Bristol Myers said it plans to engage the US Food and Drug Administration on regulatory next steps. European Medical Journal reported that the stock advanced almost 4% in pre-market trading on Monday.

Bristol Myers also reported phase 3 ALOFT-IPF results for admilparant in idiopathic pulmonary fibrosis. The trial compared 60 mg and 120 mg twice daily against placebo in about 1,255 adults. The 60 mg dose produced a statistically significant improvement in absolute change in forced vital capacity from baseline to week 52 versus placebo; the 120 mg dose slowed decline but was not statistically significant. Bristol Myers said safety and tolerability were favourable, with discontinuations due to adverse events low and similar to placebo. Pharmaphorum noted the lack of a dose-response relationship may raise questions. This non-oncology readout shows the pipeline's mixed late-stage outcomes, although it sits outside the oncology focus.

Drug data versus investor expectations

The pattern across these readouts is that drug-level success and share price reaction have not always aligned. The EXCALIBER-RRMM result delivered a 22-month absolute improvement in median progression-free survival, yet Bristol Myers shares fell 1.41% that day. The RYZ101 announcement, which did not include an effect size, was followed by a nearly 4% pre-market share rise. The sources do not explain the reasons for the moves.

What the readouts do show is an oncology pipeline with multiple late-stage positive signals. Zenbexus now has confirmatory data to support its accelerated approval. The Biokin ADC adds a signal in genetically-defined lung cancer, though limited details are public. RYZ101 provides a milestone from the RayzeBio acquisition and moves toward regulatory discussions. For clinicians, the Zenbexus data give an absolute difference in median progression-free survival of 22 months; for investors, each asset is weighed against commercial expectations and broader portfolio risks, and the share reactions have diverged.