Daiichi Sankyo to Accelerate BLA Submission for DS-8201

Daiichi Sankyo has announced that it is accelerating its Biologics License Application (BLA) for DS-8201, [fam-] trastuzumab deruxtecan for the treatment of patients who previously received ado-trastuzumab emtansine (T-DM1; Kadcyla), to the first half of 2019. [Fam-] trastuzumab deruxtecan is an antibody—drug conjugate (ADC) designed to delivery cytotoxic chemotherapy to cancer cells via a human epidermal receptor 2 (HER2) antibody attached to a novel topoisomerase I inhibitor payload and a tetrapeptide-based linker.

“We are pleased to confirm the acceleration of the [fam-] trastuzumab deruxtecan clinical development program for this potential indication in patients with HER2-positive metastatic breast cancer pretreated with T-DM1 ahead of schedule,” Antoine Yver, MD, MSc, executive vice president and global head of oncology research and development at Daiichi Sankyo, said in a statement. “Simultaneously, we are committed to our aggressive development strategy evaluating the potential of [fam-] trastuzumab deruxtecan across a spectrum of HER2-expressing cancers including breast, gastric, lung and colorectal.”

The company revealed that the initial BLA for the ADC will include results from its pivotal phase 2 study, DESTINY-Breast01, results of which are scheduled for presentation at an upcoming medical conference. The study, completed in September 2018, is a 2-part, open-label, global, multicenter study evaluating the safety and efficacy of DS-8201 in patients with HER2-positive unresectable and/or metastatic breast cancer (MBC) previously treated with ado-trastuzumab emtansine, and its primary end point it objective response rate.

The ADC is also in a pivotal phase 3 study in previously treated HER2 low-expressing MBC versus the investigator’s choice (DESTINY-Breast04), a phase 3 study in HER2-positive MBC versus ado-trastuzumab emtansine (DESTINY-Breast03), and a phase 3 study in HER2-positive MBC versus the investigator’s choice post ado-trastuzumab emtansine (DESTINY-Breast02).

Separately, the company announced that it will partner with AstraZeneca to develop and commercialize DS-8201 in many countries worldwide. The deal sees AstraZeneca paying Daiichi Sankyo up to $6.90 billion in total (inclusive of $1.35 billion upfront and up to $5.55 billion on achievement of relevant milestones).

In a statement, Pascal Soriot, chief executive officer of AstraZeneca, said of its company’s sizable investment, “We believe that [fam-] trastuzumab deruxtecan could become a transformative new medicine for the treatment of HER2-positive breast and gastric cancers…[and] has the potential to redefine breast cancer treatment as the first therapy for HER2 low-expressing tumors. It also has the potential to treat other HER2-mutated or HER2-overexpressing tumors, including lung and colorectal cancers.”

If Daiichi Sankyo is successful in its program and regulatory bids for ADC, the product could spell serious competition for drug maker Roche, which had hoped to mitigate losses from biosimilar competition for its brand-name trastuzumab, Herceptin, through sales of its ado-trastuzumab emtansine and its pertuzumab (Perjeta), which is used in combination with trastuzumab. Daiichi Sankyo already competes with Roche in Japan, where in late 2018, it launched its biosimilar trastuzumab, trastuzumab BS, as part of its biosimilar partnership with Amgen.