AstraZeneca’s $7B bet on Daiichi Sankyo’s antibody drug conjugate pays off with pivotal data to back their regulatory pitches
Buoyed by the performance of its oncology drugs, in March AstraZeneca chief Pascal Soriot bet big to partner with Daiichi Sankyo on its experimental breast cancer drug, with $1.35 billion upfront in a deal worth up to roughly $7 billion. On Wednesday, the Japanese drugmaker said the therapy had cleared a pivotal mid-stage study, paving the way for regulatory submissions in the first half of fiscal 2019.
The drug, trastuzumab deruxtecan, 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. About 30% of breast cancers are HER2 positive, according to the NIH’s National Cancer Institute. Despite treatment with trastuzumab (Roche’s Herceptin), pertuzumab (Roche’s Perjeta), and T-DM1 (Roche’s Kadcyla) — many breast cancer patients continue to see their disease progress, the company said.
In the phase II DESTINY-Breast01 trial, trastuzumab deruxtecan was evaluated in patients with HER2-positive unresectable and/or metastatic breast cancer, who disease had progressed despite Kadcyla therapy. The main goal of the 253-patient study was objective response rate, while secondary endpoints included duration of response, progression-free survival and overall survival.
As assessed by an independent review committee, the response-rate in the heavily-pretreated global patient population mirrored the “unprecedented” clinical activity in the recently published phase I trial, in which a large proportion of patients achieved disease control, and a long duration of response, Daiichi said.
In this early-stage study, the first portion of the trial was dedicated to finding the optimal dose of the drug to use in the second tranche of the trial. From the evaluable 111 patients in the second phase of the trial — 66 achieved a confirmed objective response; and 104 experienced confirmed disease control, with a median follow-up of 9·9 months. The median duration of response was 20·7 months, the median progression-free survival was 22·1 months and tumour shrinkage was observed in 102 patients with measurable lesions who had at least one postbaseline scan. From a safety and tolerability perspective, evaluated patients had one or more treatment-emergent adverse event of any grade.
Detailed results from the mid-stage study will be presented at an upcoming medical meeting.
“These results confirm our commitment to pursue accelerated regulatory pathways in HER2 positive metastatic breast cancer…” said Antoine Yver, global head of oncology R&D at Daiichi Sankyo, in a statement.
Trastuzumab deruxtecan, which has secured breakthrough therapy status and fast track designation from the FDA, is an HER2-targeted ADC with a topoisomerase I inhibitor payload — a chemotherapeutic agent designed to interrupt DNA replication in cancer cells. It is being developed for other HER2-expressing cancers including gastric cancer, with an added focus on non-small cell lung and colorectal cancer.
If approved, Daiichi will book drug sales in the United States and certain countries in Europe, in addition to other markets where it has affiliates — while AstraZeneca $AZN will book sales in all other global markets, including China, Australia, Canada and Russia.
Soriot unveiled the Daiichi tie-up months after executing a restructure of its R&D by dismantling the MedImmune name and dividing development operations between cancer — under new arrival Jose Baselga — and everything else under Mene Pangalos.