Breast cancer approval in tow, AstraZeneca, Daiichi armed antibody scores in key gastric cancer study
AstraZeneca kicked off Monday with a flurry of good news. Apart from unveiling positive results on its stroke trial testing its clot-fighter Brilinta, and welcoming its experimental IL-23 inhibitor brazikumab back from Allergan — the British drugmaker also disclosed some upbeat gastric cancer data on its HER2-positive oncology therapy it is collaborating on with Daiichi Sankyo.
Buoyed by the performance of its oncology drugs, last March AstraZeneca chief Pascal Soriot bet big to partner with Daiichi on the cancer drug, with $1.35 billion upfront in a deal worth up to roughly $7 billion. Roughly 8 months later, as 2019 drew to a close, the FDA swiftly approved the drug — trastuzumab deruxtecan — for use in breast cancer, months ahead of the expected decision date.
Trastuzumab deruxtecan, branded as Enhertu, is an antibody-drug conjugate (ADC) — therapeutics in which a cancer-killing toxin is attached to a specific antibody using a biodegradable linker — for cancers that express HER2, a protein associated with aggressive disease that often resides on certain breast cancer cells. Roughly one in five gastric cancers are HER2 positive, AstraZeneca said.
The pivotal mid-stage trial, DESTINY-Gastric01, tested Enhertu against chemotherapy in 189 patients from Japan and South Korea with HER2-expressing advanced gastric cancer or gastroesophageal junction adenocarcinoma, whose disease progressed despite two or more prior treatment regimens including fluoropyrimidine and platinum chemotherapy and trastuzumab.
The trial met the main goal of inducing statistically significant improvement in objective response rate (ORR), as well as the key secondary endpoint of overall survival. Detailed data are still to come.
Whilst a smaller indication than HER2+ metastatic breast cancer, this still represents a significant opportunity with an estimated roughly 10,000 HER2+ metastatic gastric cancer patients in the US, top 5 EU markets and Japan, Jefferies’ analyst Peter Welford wrote in a note.
Welford’s $2.05 billion in risk-adjusted global peak sales for Enhertu is predominantly based on the therapy’s other indications, particularly metastatic breast cancer, he said, adding that just $330 million of that accounts for gastric cancer.
Most patients diagnosed with gastric cancer present with advanced, incurable disease — trastuzumab in combination with chemotherapy is typically the first line of defense in patients with metastatic HER2-positive gastric and gastroesophageal cancer. Once the disease no longer responds to trastuzumab — patients have limited options.
Daiichi, which expects the drug to reap peak sales up to $4.5 billion across different indications, is on track to take forward the drug’s application initially in Japan where gastric cancer is highly prevalent. Enhertu is an HER2-targeted ADC with a topoisomerase I inhibitor payload — a chemotherapeutic agent designed to interrupt DNA replication in cancer cells, and is also being tested in other cancers.
In 2015, Roche’s Kadycla, known chemically as trastuzumab emtansine, failed to elicit any benefit in patients previously treated for HER2-positive advanced gastric cancer. Last April, Merck’s star PD-1 therapy Keytruda failed to position itself in the frontline gastric cancer setting, although it has already secured approval as a third-line treatment.