Seattle Genetics will soon seek U.S. approval for an experimental breast cancer drug it acquired in a 2018 deal for Cascadian Therapeutics, announcing Monday the success of a study testing the treatment in patients with a certain type of advanced breast cancer.Patients given the drug, called tucatinib, along with Roche’s Herceptin and a common chemotherapy went longer without dying or their disease progressing than patients who were put on just Herceptin and chemo, handily meeting the goal of the study. Detailed data will be presented at the San Antonio Breast Cancer Symposium in December, Seattle Genetics said.Shares in Seattle Genetics rose by nearly 15% to reach an all-time high of about $100 each, valuing the Seattle-based biotech at over $17 billion.
An oral kinase inhibitor, tucatinib targets the cell surface protein HER2, which is overexpressed in approximately 15% to 20% of advanced breast cancer cases and linked with tumor spreading. Attacking HER2 is the therapeutic strategy behind Herceptin as well as drugs like Perjeta (pertuzumab) and Kadcyla (ado-trastuzumab-emtansine), all of which are made by Roche.
In HER2CLIMB, Seattle Genetics tested adding tucatinib to treatment with Herceptin and capectitabine in patients who had previously been treated with Herceptin, Perjeta and Kadcyla.
Study participants given the triple combination were 34% less likely to die, and 46% less likely to experience disease progression than those who received Herceptin and capecitabine — results that led Seattle Genetics to decide to unblind the study and offer tucatinib to patients on the control arm.
Importantly, treatment with the tucatinib-containing regimen appeared to benefit patients whose cancers had metastasized to the brain.
Still, adding Seattle Genetics’ drug did result in increased rate of side effects, in particular diarrhea and liver enzyme elevations. Nearly 6% of patients on tucatinib discontinued due to adverse events, compared to 3% of those on the double regimen.
The positive findings from HER2CLIMB support Seattle Genetics’ approach in developing tucatinib as an add-on drug to Herceptin.
“Unlike other HER2 agents that have primarily attempted to displace Herceptin for market share in similar settings, [Seattle Genetics] has strategically chosen to piggyback on Herceptin’s success,” wrote SVB Leerink analyst Andrew Berens in a Oct. 21 note to clients.
“While it is an extremely high bar clinically to demonstrate increased efficacy over Herceptin via dual HER2 blockade, we believe this strategy could lead to significant commercial success, especially as biosimillar Herceptin emerges,” he added.
Puma Biotechnology and Macrogenics are also, respectively, developing the HER2-targeting cancer drugs Nerlynx (neratinib), which was approved in 2017, and margetuximab, set to be submitted to regulators later this year.
Yet a more formidable disruptor to the HER2 breast cancer market might be AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate trastuzumab deruxtecan, which the companies recently announced was accepted by the Food and Drug Administration for review.