The promise shown by Ambit Biosciences' quizartinib, which is partnered with Astellas, as a treatment for acute myeloid leukaemia, has caused a stir at the American Society of Hematology meeting in Atlanta.

Final results of a Phase II study of quizartinib were presented which suggest the drug may be an excellent option to treat a subset of patients with treatment-resistant AML. In the study, the majority carried a mutation in a gene called FLT3-ITD and presenting the data at ASH, Mark Levis of Johns Hopkins University, noted that the FLT3 mutation is a "power switch" that leukaemia cells use to spread more aggressively, which helps them to grow back immediately after chemotherapy.

He added that the only way to treat this type of mutation "is to find a way to turn the switch off - a feat that has eluded researchers for far too long". While patients with the FLT3-ITD mutation can achieve remission with standard chemotherapy, they tend to relapse very quickly. Furthermore, an important treatment option is a stem cell transplant, but only if the patient is in some form of remission, otherwise, failure rates are high.

Quizartinib 'turns off' mutated gene

Quizartinib is designed to 'turn off' the mutated FLT3 enzyme, and researchers conducted the study among 333 patients divided into two cohorts. In the second cohort, involving 137 patients (99 with mutation and 38 without), a complete remission rate of 44% was observed in patients with the FLT3-ITD mutation with a median duration of response of 11.3 weeks and median overall survival of 23.1 weeks. Even in those patients without the mutation, researchers observed a 34% complete response.

Quizartinib, which is available in oral liquid form, was well tolerated, and Dr Levis noted that it is "the first and only single-agent drug that has produced a clinical benefit in AML patients with this deadly mutation who have failed previous therapy". He added that the number of patients "bridged to a stem cell transplant was very significant"; of the aforementioned 137 patients, 47 were able to receive a transplant after responding to quizartinib and 18 had survived 60 weeks after treatment with no disease recurrence.

The results were described as remarkable at an ASH press briefing and Dr Levis said that Phase III trials "will hopefully lead to the approval of quizartinib to make it accessible to those patients who previously had no hope for a cure".

Privately-held Ambit and Astellas linked up three years ago to develop FLT3 kinase inhibitors in cancer and non-oncology indications. Ambit pocketed $40 million upfront and could bank up to $350 million in pre-commercialisation milestones, plus double-digit royalties; it has an option to co-promote and share profits in the USA.