FDA starts quick review of Astellas/Seattle Genetics’ bladder cancer drug

The FDA has started a priority review of Seattle Genetics and Astellas’ antibody-drug conjugate enfortumab vedotin in bladder cancer, setting up a possible approval next March.

The US regulator is considering use of the Nectin-4-targeting ADC as treatment for advanced urothelial carcinoma (UC) – the most common form of bladder cancer – after the failure of chemotherapy and cancer immunotherapy.

Seattle and Astellas filed for approval of enfortumab vedotin in July on the strength of a phase 2 trial – reported at this year’s ASCO congress – in patients with UC who had received platinum-based chemotherapy and treatment with a PD-1/PD-L1 inhibitor.

The study (EV-201) showed that the ADC produced a clinical response in 44% of treated patients, with 12% of them having a complete response. The median duration of response was 7.6 months, and progression-free survival (PFS) came in at 5.8 months with median overall survival of 11.7 months.

To put that in perspective, first-line chemotherapy for advanced UC will typically achieve a response in two-thirds of patients, while immunotherapy – currently approved as a second-line treatment option or first-line in chemo-ineligible patients – has a response rate of around 25%.

The FDA previously gave enfortumab vedotin a breakthrough designation for UC patients whose cancer progressed despite checkpoint inhibitor therapy, on the grounds that they have few remaining treatment options.

Checkpoint inhibitors have transformed the treatment of bladder cancer, ending a 30-year drought in new therapies when Roche’s Tecentriq (atezolizumab) became the first drug in the class to be approved for the disease in 2016.

Since then Tecentriq has been joined in the second-line setting by Merck & Co/MSD’s Keytruda (pembrolizumab), Bristol-Myers Squibb’s Opdivo (nivolumab), AstraZeneca’s Imfinzi (durvalumab) and Merck KGaA/Pfizer’s Bavencio (avelumab).

Tecentriq and Keytruda also have approval in chemo-ineligible patients and have generated data that could extend first-line use in combination with chemo.

Enfortumab vedotin was described at ASCO as “an important step forward in the management of relapsed bladder cancer” that in some cases exceeds the [data] seen with checkpoint inhibitors,” according to Kantar’s Len Kusdra.

Meanwhile, other new drugs are coming through the pipeline that could provide further options for relapsed patients, including Immunomedics’ TROP2-targeted ADC sacituzumab govitecan which also had positive phase 2 results.

Johnson & Johnson also claimed the first approval for a targeted second-line therapy for bladder cancer when it got the nod from the FDA for Balversa (erdafitinib) in April for advanced UC with genetic mutations known as FGFR3 or FGFR2.