Merck KGaA has said it will no longer seek approval for its solid tumour candidate evofosfamide after two phase III trials failed to show efficacy.
The decision was taken after evofosfamide (TH-302) failed to show any improvement in overall survival in the trials, which involved patients with metastatic pancreatic cancer and soft tissue sarcoma who received the drug in combination with chemotherapy.
The revelation – coming less than a month after Merck finalised a co-promotion deal for the drug – had a dramatic impact on evofosfamide’s original developer Threshold Pharmaceuticals.
The US biopharma company saw its share price fall 85% on the day of the announcement, with chief executive Barry Selick telling investors that it will make a decision on ongoing and pending evofosfamide trials in the near future.
Evofosfamide is an investigational hypoxia-activated prodrug, designed to be inert in the body until it comes into contact with the low-oxygen environment in solid tumours. Merck first took a license to the drug in 2012 in a $525m deal.
“Despite seeing signs of activity in pancreatic cancer, pre-specified primary endpoints were not met in both studies and therefore the data do not support filing in these indications,” said Merck’s head of global R&D Luciano Rossetti in a statement.
“We will be making a quick decision on the future of the ongoing evofosfamide clinical programme,” he added, noting that Merck will redeploy resources into other projects such as Pfizer-partnered immuno-oncology drug avelumab.
If evofosfamide is deemed terminal, Threshold will focus on tarloxotinib, a prodrug designed to selectively release an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor under severe hypoxia conditions, which is in two phase II trials.
The big question now is whether the strategy of harnessing hypoxia as a delivery trigger for cancer therapies adopted by Threshold is undermined by the results or whether the disappointing results with evofosfamide are compound-specific.
Preliminary data on tarloxotinib are due in the first half of next year, said Selick, but in the meantime “we will be thoughtfully evaluating strategic options pertaining to the future of the company”.