With Roche’s HER2-positive breast cancer drug Herceptin (trastuzumab) facing imminent patent expiration in the U.S., pharmaceutical firms are accelerating to develop antibody-drug conjugates (ADCs).
HER2 is a tyrosine kinase receptor growth-promoting protein, associated with aggressive disease and poorer prognosis in breast cancer patients. ADCs are targeted therapies combining monoclonal antibodies with cancer-killing cytotoxic drugs.
|Roche’s Kadcyla, an antibody-drug conjugate to treat patients with HER2-positive breast cancer|
Roche is working on the next-generation Kadcyla (trastuzumab emtansine), and AstraZeneca and Daiichi Sankyo, on DS-8201 (trastuzumab deruxtecan).
Roche said on May 6 that the U.S. Food and Drug Administration granted Kadcyla for the adjuvant treatment of patients with HER2-positive early breast cancer who have the residual invasive disease after neoadjuvant taxane-Herceptin therapy.
Kadcyla is the first ADC that combined Herceptin with cytotoxic anti-cancer agent emtansine to target HER2-positive breast cancer. The medicine obtained a license for HER-positive metastatic breast cancer in the U.S. in 2013. Now, Kadcyla can also be used for patients with early breast cancer as a pre-operative treatment.
Herceptin, which generates a significant portion of Roche’s revenue, will have its patent expired in the U.S. in June. Analysts have expected numerous biosimilars to arrive in the market to replace Herceptin.
Roche was able to get Kadcyla’s expanded indication 12 weeks after using the FDA’s Real-Time Oncology Review pilot program.
The latest approval was based on the phase-3 KATHERINE study, which compared Kadcyla with Herceptin in HER2-positive early breast cancer patients who had residual invasive cancer after neoadjuvant taxane-Herceptin, pre-operative treatment.
The study outcomes showed that the risk of recurrence and death in the Kadcyla-treated group was reduced by 50 percent, compared with the Herceptin group. Over 88 percent of the Kadcyla-treated patients did not have a recurrence in the third year after the treatment, versus 77 percent of the Herceptin group.
Adverse reactions with Grade 3 or higher occurred 26 percent of the Kadcyla group, versus 15 percent in the Herceptin Group. The most common Grade 3 or higher adverse reactions were thrombocytopenia (6 percent) and hypertension (2 percent).
AstraZeneca and Daiichi Sankyo are betting on DS-8201, an ADC to target HER2-positive breast cancer to treat those who fail in Roche’s Kadcyla therapy.
On Wednesday, the two companies announced positive top-line results of the phase-2 DESTINY-Breast01 trial on DS-8201 and said they would seek U.S. approval in the second half of the year.
DS-8201 drew much attention at the American Society of Clinical Oncology last year when it showed unusually impressive phase-1 study results. The investigational drug reduced tumors dramatically in HER2-expressing cancer including metastatic and recurrent breast cancer and gastric cancer.
The DESTINY-Breast01 trial aims to evaluate DS-8201 in patients with HER2-positive unresectable or metastatic breast cancer, whose disease had progressed despite Kadcyla treatment. Recently, DS-8201 met the first-part primary endpoint.
Based on the study results, AstraZeneca and Daiichi Sankyo said they would file the Biologics License Application (BLA) with the FDA for DS-8201 and seek approval from all the drug regulators around the world in the second half.
DS-8201 won the FDA Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer.
Filing of the BLA in the second half and the FDA’s fast track review will allow the drugmakers to roll out the medicine in the first half of next year, observers said.