AZ, Daiichi Sankyo get early okay for DS-8201, now named Enhertu

The FDA has given an early Christmas present to AstraZeneca and Daiichi Sankyo by approving their DS-8201 for HER2-positive breast cancer well ahead of schedule.

The US regulator has cleared the HER2 inhibitor drug – now known as Enhertu (trastuzumab deruxtecan) – for metastatic HER2-positive disease in patients who have previously been treated with two or more anti-HER2 based regimens.

Enhertu is one of a crop of new HER2-targeting drugs that aim to challenge Roche’s long-dominant position in HER2-positive breast cancer with its triumvirate of Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine).

Antibody-drug conjugate Enhertu is competing most closely rival with Kadcyla – also an ADC – in the third- and later-line therapy HER2 category, but AZ and Daiichi have made no secret of their intention to move their drug further up the treatment pathway.

This first regulatory approval is based on the DESTINY-Breast01 trial in patients who had previously been treated with Herceptin, Perjeta or Kadcyla. Enhertu achieved a 60% objective response rate, including just over 4% complete responses, with a median duration of response of 14.8 months.

AZ and Daiichi Sankyo are also conducting three additional phase 3 trials in HER2-positive breast and gastric cancer settings, as well as in low HER2-expressing tumours that could dramatically expand the potential market for the drug. Analysts think that could unlock peak sales in excess of $4bn a year.

The earlier-than-expected FDA approval is a big bonus for AZ, which wagered a whopping $1.35bn upfront to license the drug earlier this year in a deal that could eventually be worth up to $6.9bn if development and sales milestones are met.

The US approval sparks a $125m payment to Daiichi Sankyo from AZ – the first milestone payment in the alliance. Sales of Enhertu in the US will be booked by Daiichi Sankyo with AZ claiming a share of gross profits.

Kadcyla is the smallest product in Roche’s HER2 portfolio, but has started to enjoy an acceleration in sales thanks to approval for the of adults with HER2-positive early breast cancer, in addition to its established use as an adjuvant treatment in patients who fail Herceptin treatment.

In the meantime, further HER2 competition could be coming from Seattle Genetics’ oral drug tucatinib, which recently cleared the phase 3 HER2CLIMB trial as an add-on to Herceptin plus Roche’s chemotherapy Xeloda (capecitabine) in patients previously treated with Roche’s trio of HER2 drugs.