FDA backs Astellas/Seattle Genetics bladder cancer drug

The FDA has quickly okayed Astellas and Seattle Genetics’ advanced bladder cancer drug enfortumab vedotin, one of the stars of this year’s ASCO conference that was considered an almost dead cert for approval at the event in June.

Branded as Padcev (enfortumab vedotin-ejfv), the drug is the first approved for locally advanced or metastatic urothelial cancer after treatment with platinum-based chemo and a PD-1/L1 inhibitor.

It will be priced between $110,000 to $120,000, although this will depend on a patient’s weight and how long they stay on treatment, and government discounts for older patients are likely to bring the cost down to around $90,000.

Padcev was approved conditionally using an accelerated approval based on earlier stage data – in this case tumour response rate – with continued approval depending on survival data from a larger trial.

The drug is a first-in-class antibody directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.

Approval was based on the single-arm phase 2 trial involving 125 patients with locally advanced or metastatic urothelial cancer whose disease had progressed after prior treatment with a PD-1 or PD-L12 – such as Merck & Co’s Keytruda and AstraZeneca’s Imfinzi - and platinum-based chemotherapy.

A blinded independent review found a response rate of 44%, with a complete response rate of 12% and a partial response rate of 32%.

The median duration of response was 7.6 months, and the most common serious adverse reactions included urinary tract infection (6%) and cellulitis (5%).

The most common adverse reactions included fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%) and alopecia (50%).

The companies have already begun a global phase trial to confirm efficacy and support further filings with other regulators.

Padcev is an antibody-drug conjugate, which works by binding with Nectin-4 expressing cells and releasing the anti-tumour agent monomethyl auristatin E into the cell.

This stops the cell from dividing and induces programmed cell death.