Seattle Genetics gets US approval for oral HER2 breast cancer drug Tukysa

Seattle Genetics has claimed an earlier-than-expected approval from the US FDA for Tukysa, its third product and its first small-molecule drug.

The green light for HER2 ty­ro­sine ki­nase in­hibitor (TKI) Tukysa (tucatinib) is for its use in combination with Roche’s HER2 antibody Herceptin (trastuzumab) and chemotherapy drug Xeloda (capecitabine) in patients who have been treated with one or more prior anti-HER2 drugs.

Analysts said that could cover the use of the orally-active drug as a second-line therapy and potentially also after neoadjuvant (pre-surgery) and adjuvant (post-surgery) treatment with HER2 drugs to stop the cancer recurring.

The approval comes on the back of the HER2CLIMB trial, which found that adding Tukysa to Herceptin and Xeloda therapy achieved a 46% reduction in the risk of disease progression or death compared to the two Roche drugs given alone, as well as a 34% reduction in the risk of death.

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

One key characteristic of Tukysa is that it can cross the blood brain barrier and so should be effective in patients whose cancer has spread to the brain, and that is borne out in the HER2CLIMB trial, where almost half (48%) of patients had brain metastases.

Analysts at SVB Leerink have previously predicted that sales of Tukysa could reach $400m a year in the second-line indication alone, with its efficacy in brain metastases giving it a route to earlier-line use even ahead of formal regulatory approval.

They now think the drug could be a $1.2bn product by 2030. Given that Seattle Genetics licensed tucatinib from Cascadian Therapeutics last year in a deal valued at $614m, that now looks like a great deal.

If the analysts’ predictions are accurate, Seattle Genetics will have three drugs on the market with blockbuster potential. It has been selling antibody-drug conjugate Adcetris (brentuximab vedotin) for lymphoma since 2001, and cleared the $1bn threshold last year with the US company booking $628m of that total from North American sales.

At the end of last year the company also bagged FDA approval for Padcev (enfortumab vedotin), another ADC for bladder cancer that has also been topped for $1bn-plus sales.

Competition in the HER2 category is heating up though, with a new HER2-targeting ADC from Daiichi Sankyo and AstraZeneca – trastuzumab deruxtecan – approaching a possible approval in the US in the next few weeks.

Seattle Genetics says it is pricing the drug at $18,500 for a 30-day supply, making the average cost of a course of treatment to $111,000 per patient.