Astellas' Padcev and Gilead's Trodelvy grab key EU approvals

Two antibody-drug conjugates – Astellas' Padcev and Gilead's Trodelvy – have claimed new approvals in bladder cancer and triple-negative breast cancer, respectively, from the EMA.

The combination of anti-nectin-4 ADC Padcev (enfortumab vedotin) with MSD's PD-1 inhibitor Keytruda (pembrolizumab) has become the first regimen to be cleared in the EU for use before and after surgery for patients with muscle-invasive bladder cancer (MIBC) who can't be treated with the standard perioperative regimen of cisplatin plus gemcitabine.

Meanwhile, TROP2-directed ADC Trodelvy (sacituzumab govitecan) has had its label extended to include first-line treatment of TNBC in patients who are not eligible for standard PD-1/PD-L1 inhibitor immunotherapy. Around 60% of patients with metastatic TNBC fall into that category, and previously their only option was chemotherapy.

Both new indications are seen as important growth drivers for the products, as well as providing much-needed new treatment options for patients.

The Padcev approval is based on the results of the EV-303/KEYNOTE-905 study, which found that Padcev plus Keytruda reduced the risk of tumour recurrence, progression, or death by 60%, outperforming surgery alone and surgery plus Keytruda, and also cut the risk of death by 50% – the first time that a systemic treatment has improved overall survival (OS) in this patient group.

Astellas and partner Pfizer, which sells the ADC in the US and other markets, have said expanding its current use in advanced bladder cancer to earlier-stage disease is the key to unlocking what they predict could be almost $3.5 billion in peak sales.

Last December, they reported the results of a second MIBC study, EV-304/KEYNOTE-B15, which found that Padcev/Keytruda also extended survival in cisplatin-eligible patients and has also formed the basis of regulatory filings.

Trodelvy's label extension stems from the ASCENT-03 trial, which showed a significant 38% reduction in the risk of disease progression or death compared to standard-of-care chemotherapy in previously untreated PD-1/PD-L1 inhibitor-ineligible TNBC patients.

For many living with metastatic TNBC – the most aggressive form of breast cancer, with a five-year survival rate of only about 15% – first-line therapy may be their only line of treatment, creating an urgent need for effective treatment options to be used as early as possible, said Gilead.

Gilead has additional data in hand from the ASCENT-04 study, currently under regulatory review by the EMA, that could further extend the label of Trodelvy to include first-line use in combination with Keytruda as a frontline therapy for advanced TNBC.

The company is trying to fend off a challenge from AstraZeneca and Daiichi Sankyo's rival TROP2 ADC Datroway (datopotamab deruxtecan), which picked up an FDA approval last month as a first-line treatment for PD-1/PD-L1 inhibitor-ineligible TNBC.

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