Seattle Genetics wins FDA priority review for oral HER2 drug

If approved will compete with AZ/Daiichi Sankyo's Enhertu

Seattle Genetics has scored a US Food and Drug Administration priority review for its oral HER2 inhibitor tucatinib in breast cancer, setting it up for a regulatory decision in August.

Seattle is seeking approval for tucatinib in combination with Roche’s anti-HER2 antibody (trastuzumab) plus Xeloda (capecitabine).

Herceptin plus Xeloda is a standard treatment regimen for HER2-positive breast cancer, in patients previously treated with Herceptin and Roche’s other HER-2 targeting drugs Perjeta (pertuzumab) and Kadcyla (ado-trastuzumab emtansine).

In the phase 3 HER2CLIMB trial of the tucatinib combination, the regimen achieved a 46% reduction in the risk of disease progression or death, compared to the treatment with Herceptin and Xeloda alone.

The drug also met the two secondary endpoints of the trial, demonstrating a 34% reduction in the risk of death and a 52% decrease in the risk of disease progression or death in patients whose cancer had metastasised into the brain at the time they were enrolled in the study.

That last endpoint is of particular significance, as around half of those with HER2-positive breast cancer develop brain tumours that can be particularly hard to treat.

If Seattle does gain approval for tucatinib, it will go on to compete with rival HER2 inhibitor Enhertu, marketed by AstraZeneca and Daiichi Sankyo.

AZ and Daiichi won an early approval for Enhertu last December, for the treatment of metastatic HER2-positive disease in breast cancer patients who have previously been treated with two or more anti-HER2 based regimens.

Roche dominates the HER2 market, with a portfolio of products that includes Herceptin, Kadcyla and Xeloda. For Seattle’s tucatinib, an approval in combination with these drugs could see it piggyback on the success of Roche’s multibillion dollar HER2 franchise.

SVB Leerink analyst Andrew Berens said Seattle’s strategy with tucatinib could lead to “significant commercial success” given the significant challenge of improving on blockbuster Herceptin’s efficacy in the therapy area, forecasting that it could eventually become a $400m-plus product.

Seattle also has an ongoing phase 3 trial – HER2CLIMB-02 – which is testing tucatinib in earlier settings, and will compare its drug to placebo in combination with Kadcyla in HER2-positive breast cancer patients who have received prior treatment with a taxane and Herceptin.