- The Food and Drug Administration on Friday approved Daiichi Sankyo and AstraZeneca's drug trastuzumab deruxtecan for heavily pretreated breast cancer, a decision that came more than three months ahead of the agency's deadline.
- The drug, which will be sold as Enhertu, combines the active ingredient in Roche's top-selling Herceptin with a toxic payload designed to destroy tumor cells. It's now cleared for use in women who test positive for a breast cancer protein called HER2, just as Herceptin is.
- AstraZeneca made a substantial bet to gain access to the drug, paying Daiichi Sankyo $1.35 billion upfront to split marketing rights for Enhertu outside Japan. The deal was unusually financed through the sale of $3.5 billion worth of the U.K. pharma's shares.
Friday's approval marked the second consecutive day the FDA granted a speedy approval to a cancer-fighting antibody-drug conjugate, the name given to therapies that pair antibodies with potent chemotherapies. On Thursday, the agency approved Seattle Genetics' Padcev (enfortumab vedotin) for advanced bladder cancer.
The two OKs extend a remarkable streak of early FDA decisions on new drugs, including fast reviews for therapies from Global Blood Therapeutics, Alnylam, Novartis, Beigene, and Vertex.
Enhertu will be used in HER2-positive patients who have progressed after treatment with two previous HER2-targeting therapies, and are either unable to be treated with surgery or have seen their cancer spread to other parts of their bodies.
Targeting HER2 has been a central component of breast cancer treatment since the approval of Herceptin (trastuzumab) in 1998. About a fifth of women who develop breast cancer also have a genetic mutation that causes overexpression of HER2 protein, making drugs targeting the protein particularly potent in this group.
In subsequent years, Roche won approvals for other HER2-targeting drugs and, more recently, companies like Seattle Genetics, Puma Biotechnology and Macrogenics have developed experimental medicines designed to add onto, or replace, Roche's older HER2 drugs.
The FDA granted accelerated approval to Enhertu on the basis of patient response to treatment in clinical studies. Daiichi and AstraZeneca will need to confirm the drug's survival benefit in a placebo-controlled trial.
Enhertu was supported by data from the DESTINY-Breast01 trial, which enrolled 184 patients. Treatment shrank tumors in 60% of patients, with 4% achieving complete remission. Patient responses lasted for a median of 15 months — notable for a group that's already been treated with similar drugs twice before.
In addition to the required confirmatory trial in this late treatment line, Daiichi and AstraZeneca are planning on moving into earlier disease settings, too. Phase 3 trials are underway, including one against Herceptin and chemotherapy in those who have progressed on Roche's Kadcyla (ado-trastuzumab emtansine), another in patients with low HER2 expression, and a head-to-head trial against Kadcyla in patients who have progressed on Herceptin.
AstraZeneca's licensing deal with Daiichi promised up to $5.6 billion in additional payments, including $3.8 billion in regulatory and other milestones and $1.75 billion in contingent payments tied to potential sales.
Approval of Enhertu triggered a $125 million payment from AstraZeneca to Daiichi. Pricing for the drug was not immediately available.