BeiGene touts 'encouraging' response rates as the Chinese biotech mounts challenge to BTK, PD-1 leaders
As BeiGene sets the stage for a pivotal showdown with the OG BTK inhibitor Imbruvica, it’s zeroing in on a subset of patients for whom their drug, zanubrutinib, could be especially helpful.
The biotech — which has origins in China — also brandished the latest pivotal results for its PD-1 drug tislelizumab, another franchise shaker that’s under priority review in China, at the EHA Congress.
Investigators took a data cut from a Phase III open-label trial that is putting zanubrutinib against Imbruvica (ibrutinib) in patients with Waldenström’s Macroglobulinemia to showcase promising response rates. A non-randomized cohort of 26 patients, who has the MYD88WT genotype of WM, all received zanubrutinib. Five of them were treatment-naïve while the others had relapsed/refractory disease.
“For these patients, who typically have poorer prognoses with lower response rates, we recognize the real need for a highly potent and selective BTK inhibitor that can sustain BTK inhibition and reduce off-target effects,” CMO Jane Huang said in a statement.
At a median follow-up of 12.2 months, the drug scored an overall response rate of 80.8%, with 53.8% of patients experiencing a partial response or better. The very good partial response rate was 23.1% while exactly one patient achieved a complete response.
Imbruvica was first approved in 2015 as a monotherapy for WM, a rare, slow-growing and incurable form of non-Hodgkin lymphoma. A combination with Rituxan was also OK’d last year based on progression-free survival results. The hazard ratio compared to Rituxan alone was an impressive 0.20 (p<0.0001).
But BeiGene is coming hard at J&J and AbbVie with zanubrutinib, which became the first drug from mainland China to win an FDA breakthrough therapy designation this January. It’s also being tested for mantle cell lymphoma.
Neither PFS nor overall survival has been reached in the WM study, though Huang added updates from an ongoing Phase I/II trial give them reason to believe that zanubrutinib can induce sustained responses, with high rates of CR/VGPR at 42%.
In that single arm trial — which started off with 77 patients but now has 61 — the estimated PFS rate at 12 and 24 months was 90% and 81%, respectively.
Meanwhile, tislelizumab has demonstrated an ORR of 87% and CR of 63% among patients with classical Hodgkin’s lymphoma who’ve averaged 3 lines of prior therapy. Twelve-month PFS was estimated at 73.8% and median PFS has not been reached at 13.9 months of median follow-up.
It’s a slight improvement from the data they presented at ASH in 2018, where they saw an ORR of 86% and CR of 61% in 70 evaluable patients — more than double the complete response rate for a leading checkpoint according to Eric Hedrick, an oncologist and BeiGene’s chief advisor on this program.
“If the majority are achieving a complete response and they were truly durable, that would be a step up in the quality of the response that we’ve typically seen in PD-1 in Hodgkin’s disease,” a cautious Hedrick told Endpoints News at the time.