Key Points:
Datopotamab Deruxtecan received approval in adult patients with metastatic EGFR-mutant NSCLC after prior treatment by the FDA.
AstraZeneca will pay an upfront payment of $45 million to Daiichi Sankyo on approval in a value of $6 billion deal.
Key Background:
1. Shift in Lung Cancer Treatment
Non-small cell lung cancer (NSCLC) represents the largest proportion of lung cancers and most common leading cause of cancer-related death globally. In the US, approximately 10–15% of NSCLC patients carry EGFR mutant tumor-driving mutations. They initially respond well to EGFR-targeting inhibitors but ultimately acquire resistance with limited alternative options remaining. Datopotamab Deruxtecan fills the current unmet medical need by offering a new therapy with a new mechanism of action.
2. Mechanism of Action
Datopotamab Deruxtecan is a second-generation antibody-drug conjugate, which provides the potency of monoclonal antibodies for tumor targeting and chemotherapeutic drug for tumor cell killing. The drug specifically targets TROP2, which is a target protein found on the majority of cancer types and also overexpressed on the majority of tumors. This drives the conjugated bound chemotherapy payload into the tumor cells. The therapy is optimized for efficacy and minimal harm to normal cells, perhaps confining side effects to those of standard chemotherapy.
3. Results of Clinical Trial
Clinical trials confirmed Datopotamab Deruxtecan to be safe and effective in decelerating the disease progression in refractory EGFR-mutant NSCLC patients. Patients receiving clinical trials for refractory EGFR-mutant NSCLC showed lasting progression-free survival, better disease control with an adequate safety profile, and overall comparable to other ADCs. These findings were pivotal in FDA fast-track approval.
4. Business Impact and Strategic Partnership
The medicine is the product of AstraZeneca and Daiichi Sankyo's 2020-established cooperative alliance. The two co-develop and co-promote a pipeline of antibody-drug conjugates under the alliance. FDA approval triggers a milestone payment of $45 million to Daiichi Sankyo and marks the success of the alliance. Approval follows Enhertu's earlier regulatory victory as their first ADC blockbuster.
5. Building the Oncology Franchise
This transaction also comes on the heels of AstraZeneca's continued success in oncology and biologics. It strengthens the company's pipeline of oncology and makes it a world leader in targeted therapies. For Daiichi Sankyo, it establishes their ADC technology platform and builds their coverage in the U.S. oncology business.
6. Looking Forward
Datopotamab Deruxtecan clearance not only impacts a specific subset of lung cancer patients but denies the broad promise of ADCs as a way of anticancer therapy. As the drug companies are yet to develop such drugs and further aim them to cancers, increasingly, more and more patients will receive more effective and less toxic therapies.