Striving to improve treatment options for Acute Myeloid Leukaemia

By Professor Tobias Arkenau, Global Head of Drug Development and Chief Medical Officer, Ellipses Pharma

If there is one thing a cancer patient wants beyond fast, effective treatment – it is hope.

Initial diagnosis is naturally frightening for patients but the realisation that their prescribed treatment is not having the desired effect is particularly devastating.

Sadly, this is not uncommon in patients with relapsed and refractory Acute Myeloid Leukaemia (AML) – a result of leukaemia cells remaining or returning post-initial treatment. It is a deadly disease with poor survival rates.

For patients in this situation – mainly elderly – resuming already tried treatment may offer little chance of success. However, there is hope and more importantly intensive scientific efforts are being made worldwide with the aim of improving treatment options.

Last week, I joined 25,000 clinicians and scientists from across the world at The American Society of Haematology (ASH) annual meeting in New Orleans where the latest research developments in the treatment of AML were presented and analysed.

At ASH, we presented Ellipses’ preliminary results of the dose escalation part of the Phase 1 / 2a first-in-human study of EP0042 in patients with AML.

EP0042 is a dual FLT3 and aurora kinase inhibitor and has been progressed by Ellipses as part of its commitment to develop novel cancer treatments.

The study recruited 29 patients with relapsed/refractory AML in the UK, Australia and the Netherlands.

The primary objective of this Phase-1/2a, multi-centre study is to investigate safety and tolerability and to establish both the MTD (maximum tolerated dose) and optimal dose of EP0042 when used as monotherapy or in combination with established standard treatments.

EP0042 has been generally well tolerated at all dose levels and no DLT (dose-limiting toxicity) has been observed up to a dose level of 170mg twice daily in a 21-day dosing schedule. The side effect profile (all grades) included febrile neutropenia, anaemia, peripheral oedema fatigue, ataxia and dizziness among others. The pharmacokinetic profile supports a twice-daily dosing.

A total of 14 patients had stable disease for several cycles and two patients responded for eight and 11 months respectively.

The study continues to recruit patients with relapsed and refractory AML in a monotherapy expansion cohort and a cohort which combines EP0042 with the standard of care drugs, Venetoclax and Azacitidine.

A regulatory submission to the US FDA has been made to open four more centres to support both the single dose and combination expansions.

Of course, the journey from promising preliminary results in a phase 1 trial to effective treatments being widely available to patients has many milestones to pass. It is why we have adopted an approach of selecting potentially exciting individual assets and have them endorsed by our Scientific Affairs Group, which comprises more than 170 oncologists worldwide, before designing the most appropriate and efficient clinical trials.

Taking this approach reduces the risk of drug development failures and will help produce drugs at speed and scale.

For patients with relapsed or refractory AML, the successful development of drugs that can be introduced earlier in the treatment sequence will give hope and may make all the difference.