New drug OTX15 shows early promise in fighting acute myeloid leukaemia
Dr Esteban Cvitkovic - Oncoethix, Lausanne, Switzerland
What is OTX15?
OTX15 is one of the bromodomain inhibitors being developed currently. It’s a very sexy area in epigenetic second generation therapy; I think it’s the most advanced in clinical development at this moment.
Why did you decide to look at haematology?
Because about three or four years ago it was found that bromodomain inhibition, which is an epigenetic regulator of transcription, was the main switch to get MYC, c-MYC, which is a very prevalent and important biologically relevant gene in cancer and all the associated genes with it. Since then we know that it is not only c-MYC, there is also something called super-enhancer genes, or genes with super-enhancers, which carry a whole bunch of stuff to determine the identity of a cell. So it started as a c-MYC story, it’s now beyond a c-MYC story.
Are you getting clinically meaningful results?
Because the first data were preclinical activity in hematologic malignancies because there is a dire medical need with limited choices in them and because the clonal nature of most hematologic malignancies means that all cells are similar, we did decide to go first in haematology because it was like upping the ante, upping the threshold, and we had very good toxicology that allowed us to start so ambitiously.
What about solid tumours?
Before having assessed the toxic limit dose we saw consistently clinical activity of a quality and duration that we did not expect so early in the trial. And with most targeted therapies there is a strong association between this kind of activity early in the development and the likelihood to go much further with it.
What about solid tumours?
Solid tumours we have not started but it’s clearly on the map because there is also a lot of biological activity preclinically in a wide array of such tumours. What is important about this specific agent is that it combines preclinically very well with a wide variety of any other available or in development cancer therapies. Since the future of the drug in terms of going through a whole game of diseases is linked to that combinability and its specific tolerance, it looks good so far. So we will expand our programme to solid tumours and paediatric tumours soon.
What should oncologists take from these results?
You should be as happy as we are because for the first time… I didn’t expect to have a pill that will control as a single agent refractory leukaemia in elderly people and I don’t think many people expected that either. So having that so far as consistent anecdotes opens the imagination for a big step ahead in those kinds of diseases.