- Interim Phase 3 data presented Tuesday at the World Conference on Lung Cancer showed Takeda Pharmaceutical's Alunbrig was better at delaying disease progression than Pfizer's Xalkori for non-small cell lung cancer (NSCLC) patients who registered positive for a certain kind of mutation and hadn't yet received therapy targeted for that mutation.
- Both Alunbrig and Xalkori inhibit a signaling protein called anaplastic lymphoma kinase, or ALK. When the gene that makes ALK rearranges, the resulting proteins don't work normally and can promote cancer — exemplified by the fact that around 3-7% of NSCLC cases stem from an ALK mutation.
- Results from the ALTA-1L trial demonstrated that, compared to Xalkori, first-line treatment with Alunbrig corresponded with a 51% reduction in the risk of disease progression or death for adults with ALK-positive locally advanced or metastatic NSCLC. More than 60% of Alunbrig-treated patients experienced a Grade 3 to 5 adverse event, with the most common being increased enzyme levels and hypertension. In the Xalkori arm, 55% of patients had a Grade 3 or higher adverse event.
Pfizer's Xalkori (crizotinib) became the first ALK-inhibitor to gain Food and Drug Administration approval in 2011. The therapy quickly became standard of care for patients with ALK-positive metastatic NSCLC, and has seen steady revenue growth each year since coming to market. But growing competition threatens that trend.
Second quarter revenue for Xalkori fell 34% year over year because of volume declines spurred by competitive pressure — a pressure emanating from big pharma rivals Roche and Novartis.
Both Swiss drugmakers have their own ALK-inhibitors, Alecensa (alectinib) and Zykadia (ceritinib), that were originally OK'd to treat patients for whom Xalkori no longer worked. Yet Roche and Novartis recently locked down first-line label expansions for their respective drugs, pitting them directly against Pfizer's product.
Alunbrig (brigatinib) joined Alecensa and Zykadia as a second-generation ALK-inhibitor with its April 2017 FDA approval. The drug's label, however, doesn't yet carry a first-line indication, keeping it a step behind rival therapies. It's a problem Takeda is looking to fix with strong clinical data.
D. Ross Camidge, Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center and the lead investigator of ALTA-1L, noted in a Sept. 25 statement from Takeda that Alunbrig could be a "key player in the first-line setting" for treating ALK-positive NSCLC.
Additionally, the design of ALTA-1L "offered enrollment to a broader population by allowing patients to participate even if they had received prior chemotherapy and enrolled patients based on local standard of care ALK testing as opposed to mandating confirmation at a central lab."
The trial itself randomized 275 patients to receive either Alunbrig or Xalkori, with 27% of all participants having received prior chemotherapy in the locally advanced or metastatic setting.
Correction: A previous version of this article misattributed the quote from Takeda's Sept. 25 statement.