Daiichi Sankyo claims speedy review for AML drug in Europe

Japan’s Daiichi Sankyo is looking at a reduced review time for its acute myeloid leukaemia (AML) drug quizartinib in Europe, the top prospect in its new oncology pipeline.

The European Medicines Agency (EMA) has given the nod to an accelerated assessment for quizartinib – a second-generation FLT3 inhibitor – as a second-line therapy for adult AML patients with FLT3-ITD mutations, a particularly aggressive form of the cancer. It’s also started its review of the drug which means quizartinib could get a green light around the middle of next year.

If approved, quizartinib will join Novartis’ Rydapt (midostaurin),  which is currently the only FLT3 inhibitor on the market and was cleared by the US and EU regulators for newly-diagnosed FLT3-positive AML last year.

Rydapt’s effects are modest however, and quizartinib is one of a handful of second-generation FLT3 inhibitors that aim to provide a second-line of therapy for patients with relapsed or refractory FLT3-ITD-positive AML – a group for which there are currently no approved options. Along with the EU, quizartinib has also been submitted for approval in Japan – where it is also under accelerated review - and should be filed in the US before the end of the year. The FDA has awarded the drug breakthrough status.

Quizartinib’s marketing applications are backed by the QuANTUM-R trial, which showed that the drug prolonged overall survival as an oral, single agent compared to salvage chemotherapy in adults with relapsed/refractory FLT3-ITD AML. Daiichi Sankyo says its drug is the first in its class to do achieve that objective in this setting.

Daiichi Sankyo isn’t the only company hoping to improve on Rydapt with second-generation drugs however. Astellas recently filed for approval of its FLT3 inhibitor gilteritinib in relapsed FLT3-positive AML in the US, while AROG Pharma recently started two phase III trials ongoing for its candidate crenolanib, including a head-to-head study against Rydapt in the first-line setting.

Arnaud Lesegretain, Daiichi Sankyo’s vice president, oncology R&D, said that the EU accelerated assessment “underscores the significant unmet need for patients with relapsed/refractory FLT3-ITD AML.”

It’s also another step on the path to developing a new oncology franchise at Daiichi Sankyo, a move it started several years ago. Quizartinib was added to its pipeline in 2014 when the company bought Ambit Biosciences for $410 million.

Some of its other programmes have suffered setbacks, however, including EGFR-targeted antibody nimotuzumab which was in development for non-small cell lung cancer (NSCLC) but was pulled because of toxicity issues, and HER3 inhibitor patritumab which failed a combination study with Roche’s EGFR drug Tarceva (erlotinib) in the same cancer. The company has also racked up a few failed trials for ArQule-partnered MET inhibitor tivantinib and dropped it in 2017.

Along with quizartinib, Daiichi Sankyo’s late-stage pipeline projects in cancer are CSF-1R/KIT/FLT3 inhibitor pexidartinib for tenosynovial giant cell tumours and Amgen-partnered anti-RANKL antibody denosumab for breast cancer, which is being developed for the Japanese market only.