Astellas suffers pancreatic cancer failure with Vyloy

A year ago, Astellas was celebrating the first-in-class approval of its claudin 18.2-targeting cancer drug Vyloy for gastric cancers. Now, a bid to expand its label into pancreatic cancer has hit the buffers.

The 393-patient phase 2 GLEAM study compared the combination of Vyloy (zolbetuximab) with chemotherapy (gemcitabine and nab-paclitaxel) to chemotherapy alone, but failed to show an increase in overall survival, its primary objective, in patients with metastatic pancreatic adenocarcinoma.

It is a big disappointment for patients with this form of pancreatic cancer and the doctors who treat them, as the disease is the third most common cause of cancer death in developed countries, has one of the lowest survival rates among all solid tumour types, and patients experience highly debilitating symptoms.

For locally advanced or metastatic disease – which accounts for around 80% of cases, as there is no reliable screening test for early detection – the median survival time is just five months.

"While we acknowledge that the GLEAM trial did not meet its primary endpoint, we extend our heartfelt gratitude to all trial participants for their invaluable contributions," said Moitreyee Chatterjee-Kishore, Astellas' head of oncology development.

"Our unwavering commitment to pancreatic cancer research remains firm," she continued. "We recognise the immense challenges posed by this notoriously difficult-to-treat disease and are dedicated to advancing a robust pipeline of innovative investigational treatments aimed at providing hope and improved outcomes for patients."

Vyloy is already approved for use in combination with chemotherapy for the first-line treatment of adults with locally advanced or metastatic HER2-negative, claudin 18.2-positive gastric or gastroesophageal junction adenocarcinoma that cannot be treated with surgery.

It remains the only approved claudin 18.2-targeted therapy on the market and has shown encouraging commercial uptake since its launch, with sales in the last fiscal year reaching just over JPY 12.2 billion (approximately $80 million) and adding another JPY 14 billion in the first three months of fiscal 2025 alone.

According to Astellas, the drug has made an "exceptional start exceeding expectations."

Analysts have suggested that the drug could eventually make annual sales of $1 billion or more, although achieving those levels will depend on widespread adoption of CLDN18.2 testing, which isn't routinely carried out at the moment.

Astellas acquired zolbetuximab with its takeover of Ganymed Pharma in 2016, paying around $430 million upfront in a deal with a total value of up to $1.3 billion.

Astellas is advancing in claudin 18.2 on a broad front, and later this week at the ESMO cancer conference, will present data on a bispecific T-cell engager (TCE) against the target (ASP2138) in gastric, GEJ, and pancreatic cancers.

The company also licensed rights to an antibody-drug conjugate (ADC) from Chinese biopharma Evopoint in May for $130 million upfront in a deal that could be worth up to $1.34 billion.