BeiGene's Brukinsa Fails In Head-To-Head But Hope Remains For Rare Indication
Signs Of Benefit Vs Imbruvica
Executive Summary
Days after bagging a US approval for its first global new drug, BeiGene was dealt a blow as its BTK inhibitor Brukinsa showed no significant superiority over class leader Imbruvica in Waldenström's macroglobulinemia, although the Chinese company remains hopeful for a possible approval.
BeiGene Ltd. disclosed results from the Phase III ASPEN trial that showed the company’s BTK inhibitor Brukinsa (zanubrutinib) missed its primary endpoint of superiority in terms of complete response and very good partial response (VGPR) in a head-to-head trial with AbbVie Inc.’s Imbruvica (ibrutinib).
But the Beijng-based company says it still intends to pursue discussions with regulators towards a possible approval in the study indication of Waldenström's macroglobulinemia (WM).
“Despite not reaching the primary endpoint for superiority, we feel that ASPEN provides evidence suggesting differentiation in both efficacy and safety and tolerability for zanu [zanubrutinib] in the first randomized comparative trial within the BTK inhibitor class,“ BeiGene CEO and chairman John Olyer told investors during a 17 December conference call.
The study showed that in relapsed or refractory patients, the VGPR rate as assessed by independent review committee was 28.9% in the zanubrutinib arm and 19.8% in the ibrutinib arm (no patients achieved a complete response in either arm); the difference was not statistically significant. Also, the VGPR rate for the overall patient population did not reach statistical significance.
ASPEN enrolled 229 patients with WM across 61 centers in Europe, Australia, and the US. The study had two cohorts, a randomized cohort consisting of 201 patients with an MYD88 mutation and a non-randomized cohort of 28 patients with MYD88 wild-type (MYD88WT) who received zanubrutinib because they have historically responded poorly to ibrutinib therapy.
Tolerability, Signs Of Benefit
The top-line data, however, suggested better safety and tolerability for BeiGene’s BTK inhibitor. In terms of adverse events, atrial fibrillation, minor bleeding and major hemorrhage rates were 2.0%, 48.5% and 5.9% for zanubrutinib, compared with 15.3%, 48.5% and 9.2% in the ibrutinib arm. The rate for diarrhea was 20.8% for zanubrutinib but 31.6% for ibrutinib, although neutropenia was higher for zanubrutinib (29.7%) than ibrutinib (13.3%).
“The totality of the data suggests benefit for zanubrutinib relative to ibrutinib in the treatment of Waldenström's,” Jane Huang, chief medical officer of hematology at BeiGene, told the conference call.
The company said that, despite the missed endpoint, it would pursue discussions with US and European regulators in early 2020 towards a potential green light for WM, a rare condition. “Right now, there's only one therapy approved for the disease and we've just run the largest randomized trial ever done in the disease…so I think that's going to be all our frame of mind going into the discussions," said Eric Hedrick, chief advisor and CMO of immuno-oncology.
Despite the potentially positive prospects, analysts at CICC lowered their price targets for the Hong Kong and Nasdaq dual-listed company. The securities firm cited the missed endpoint as a reason to lower the target price by 8.9% to HKD126.10 ($16.18), while maintaining a market performer rating. BeiGene was trading at just under HKD100 on the afternoon of 19 December.
US Lymphoma Approval
The US FDA on 14 November granted approval to Brukinsa for second-line use in adults with mantle cell lymphoma under the agency’s accelerated approval mechanism and three months ahead of its PDUFA schedule. (Also see "Keeping Track Of User Fee Decisions And Filings: Adakveo, Brukinsa And Fetroja Mark Massive Week Of Novel Approvals" - Pink Sheet, 17 Nov, 2019.)
BeiGene’s US commercial head Jose Neiman said that sales reps are currently focusing on raising awareness of the company and product.
The drug is also under development for other hematology conditions including in Phase III studies for chronic lymphoma leukemia (CLL) and small lymphocytic lymphoma, while a Chinese approval for relapsed CLL and mantel cell lymphoma is expected in the first half of 2020.
China PD-1 'On Track'
It’s expected that China will soon also approve tislelizumab, BeiGene's anti-PD-1 antibody, and company China GM Xiaobin Wu said the approval remains on course. (Also see "After US Approval, BeiGene Set To Gain Sixth PD-1 Green Light In China " - Scrip, 19 Nov, 2019.)
“We believe our registration approval is on track. It could be approved any day, any time. We don't know yet but it looks on track.”
If indeed approved, the Chinese firm will join Bristol-Myers Squibb Co., Merck & Co. Inc., Junshi, Innovent Biologics Inc. and Jiangsu Hengrui Medicine Co. Ltd. in marketing what would become the sixth PD-1 drug in China, and potentially the last before a second wave of PD-1s and PD-1 combinations hit the market.