Antibody-drug conjugates (ADCs) have assumed new prominence as cancer treatments in the wake of a deal between AstraZeneca Plc and Daiichi Sankyo Co Ltd of Japan to co-develop trastuzumab deruxtecan, an ADC for a group of HER2-mutated cancers.
AstraZeneca is to pay the Japanese company $1.35 billion initially for rights to the late-stage ADC candidate which received a ‘breakthrough therapy’ designation from the US Food and Drug Administration in 2017. The two companies expect to make a regulatory submission in the second half of this year.
Half of the upfront payment will be due on execution of the agreement and the other half, 12 months thereafter. In addition, the UK company has agreed to contingent payments of up to $5.55 billion which include $3.8 billion for achieving regulatory and other milestones and $1.75 billion for sales-related achievements.
ADCs are cancer drugs that consist of a monoclonal antibody linked to a cancer killing agent. The antibody targets an antigen on a cancer cell and once attached, releases the toxic agent into the cell to kill it. ADCs are in clinical development at a number of companies including Roche which received an FDA approval in 2013 for Kadcyla (trastuzumab emtansine), an ADC for late-stage breast cancer.
In gaining rights to trastuzumab deruxtecan, AstraZeneca will be competing directly with Roche. The FDA breakthrough designation for trastuzumab deruxtecan is for the treatment of patients with HER2-positive, locally-advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab, both Roche drugs, and have disease progression after the administration of Kadcyla, also developed by Roche.
The first regulatory submission for trastuzumab deruxtecan in the second half of 2019 will be for patients in the advanced or refractory breast cancer setting. The drug is also being investigated for other breast cancer indications, non-small lung cancer, gastric and colorectal cancers.
The companies will jointly develop and commercialise trastuzumab deruxtecan worldwide except in Japan where Daiichi Sankyo will have exclusive rights. The Japanese company will also be responsible for the manufacture and supply of the drug.
AstraZeneca said the upfront and near-term milestone payments will be funded from the proceeds of an equity placement amounting to $3.5 billion.
The investment in the ADC technology comes on the heels of a rethink of the company’s oncology strategy following the appointment of José Baselga as vice president for oncology research and development. Besides ADCs, AstraZeneca is building three other scientific platforms: tumour drivers and resistance, DNA damage response and immuno-oncology.
The two companies announced the collaboration on 29 March 2019.
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