New class of drugs being developed for treatment of polycythaemia vera

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An update on the progress with these newly developed drugs is provided by Associate Professor David Ross, Consultant Haematologist at Royal Adelaide Hospital and Flinders Medical Centre, Adelaide
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Treatment options for polycythaemia vera (PV) are limited at present. Hydroxyurea, a mild chemotherapy tablet, is the most widely used drug treatment in Australia, although the use of interferon is increasing since the recent PBS listing of Pegasys®. Ruxolitinib has shown good results in clinical trials in PV, but in Australia is funded only for the treatment of myelofibrosis.

In 2012 a New York research group reported that the combination of a new drug, ‘nutlin’, with interferon suppressed the growth of PV cells collected from patients.1 They did not treat patients with nutlin, but a related compound being developed by Roche has entered clinical trials as idasanutlin.

Idasanutlin is an inhibitor of MDM2, a protein involved in regulating cell growth and survival. Inhibition of MDM2 has a greater effect on the growth of PV cells than of healthy blood cells. A small Phase 1 clinical trial involving 11 PV patients treated with two different oral doses of idasanutlin was recently published in Blood, one of the leading haematology journals.2 The authors reported improved blood counts, reduction in spleen size, improved symptoms, and a reduction in the level of the JAK2 mutation in the blood.  Preliminary results from the phase 1 trial indicated that the main side effects were diarrhoea and nausea, which were usually mild and occurred in around half of people taking the drug.

A Phase 2 clinical trial of idasanutlin is now recruiting PV patients in whom hydroxyurea has caused intolerable side effects or did not achieve satisfactory disease control.3  This study is open at two Australian sites: the Royal Adelaide Hospital in South Australia and the Peter MacCallum Cancer Centre in Victoria.

Other MDM2 inhibitors are in development, including KRT232 from Kartos Therapeutics. KRT232 is being tested in PV and myelofibrosis internationally, and may become available at some Australian clinical trial sites in the coming months.

References:
1. Lu M et al. Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2, and pegylated interferon-2a specifically targets JAK2V617F-positive polycythemia vera cells Blood. 2012;120:3098-3105.
2. Mascarenhas J et al. Oral idasanutlin in patients with polycythemia vera Blood 2019; online June 5 doi: 10.1182/blood.2018893545.
3. Available at: https://www.australianclinicaltrials.gov.au

If you would like to know about the trial, please discuss this trial with your GP or specialist. You can also search for details on the Australian Clinical Trials website by typing idasanutlin into the ‘search for a clinical trial’ category.

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MPN Interferon Initiative Report

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On the 30th November, Lara Chapman represented the MPN Alliance Australia as an invited guest, at the 2nd Annual ASH Meeting, hosted in San Diego by the MPN Research Foundation. The MPN AA would like to thank our partner organisation, MPN RF, for the invitation. We appreciate the opportunity to follow up on the progress being made on this project on behalf of the donors who have supported the MPN AA.

The meeting convened to hear updates on the progress from the Grantees of the MPN Interferon Initiative. Although, the meeting was very scientific as researchers reported to their peers, the overarching feeling as an observer, was one of positivity and hope for new information and progress being made. As a patient, it was encouraging to witness the sharing of information and respect amongst the scientific community. Project Manager, Mr Richard Winneker and the MPN RF are to be congratulated on establishing such a positive research environment, and we can only hope that through sharing of resources and information, that greater progress and outcomes will be forged.

The MPN AA contribution to the MPN Interferon Initiative directly supports research here in Australia. Dr Steven Lane’s laboratory is based in Brisbane. Dr Lane (QIMR Berghofer Medical Research Institute) collaborates with Dr Ann Mullally (Brigham & Women’s Hospital) and Dr Michael Milsom (German Cancer Research Centre).

The aims of their project are outlined in the slide below.  (IFN refers to Interferon).

Achievements in the first 12 months are:

  • Validated CRISPR/Cas9 in vivo gene editing studies to develop and validate clinically relevant models of MPN disease progression (published)
  • Mechanistic understanding of interferon on Jak2 V617F stem cells (completed/ manuscript in preparation)
  • Acquisition and validation of Ropeginterferon (experiments ongoing)

Of particular interest is the finding that Ropeginterferon to date has shown superior durability of action, tolerability and efficacy compared to Pegasys and other forms of Interferon.

We look forward to hearing more as the project progresses.

Lara Chapman

 

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MPN AA donates $20,000 to MPN Interferon Initiative

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The MPN Alliance Australia is proud to announce that they have donated a total of $20,000 to support the MPN Interferon Initiative.

In April 2018, the MPN (Myeloproliferative Neoplasms) Research Foundation (MPNRF) and MPN Alliance Australia (MPN AA) announced a research partnership focused on the MPN Interferon Initiative. MPNRF and MPN AA are both patient advocacy organizations who work on behalf of patients with myeloproliferative neoplasms, a group of rare, chronic blood cancers.

The MPNRF Interferon (IFN) Initiative is a multi-center project which will bring together internationally recognized experts in both blood and solid tumors to determine how cytokine-driven pathways affect the trajectory of the MPNs, a closely-related group of progressive blood cancers. The collaboration among this group of scientists is unprecedented and speaks to their drive to answer this question, which could have wide-ranging impact on the lives of people living with cancer.

The MPN AA’s donation is directly supporting research by Dr Steven Lane in Brisbane as part of the Interferon Initiative in partnership with MPN Research.

We would like to thank the community for the support and donations towards this important research initiative.

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New research partnership

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Chicago, IL and Australia

The MPN (Myeloproliferative Neoplasms) Research Foundation (MPNRF) and MPN Alliance Australia (MPN AA) are proud to announce a research partnership focused on the MPN Interferon Initiative. MPNRF and MPN AA are both patient advocacy organizations who work on behalf of patients with myeloproliferative neoplasms, a group of rare, chronic blood cancers.

The MPNRF Interferon (IFN) Initiative is a multi-center project which will bring together internationally recognized experts in both blood and solid tumors to determine how cytokine-driven pathways affect the trajectory of the MPNs, a closely-related group of progressive blood cancers. The collaboration among this group of scientists is unprecedented and speaks to their drive to answer this question, which could have wide-ranging impact on the lives of people living with cancer.

About this partnership, Barbara Van Husen, President of MPNRF says “We are thrilled to have joined forces with a group outside of the United States in order to bring clarity to how Interferon works, why it works for some MPN patients but not others, and how to expand its capabilities and extend its use if possible. We have long operated under the model that collaboration among patient advocates is the only way forward to help all patients.”

MPN AA says “We are pleased to have partnered with MPNRF for the benefit of the global MPN Community. We are honored to contribute towards Australian based MPN Research and see the Interferon Initiative as a worthy cause. We know that some patients are unable to take advantage of this treatment due to side effects and others have a poor response.

“We are hopeful that this research initiative will help overcome these limitations to provide better treatment options. The MPN Alliance Australia is a small volunteer advocacy team of MPN patients. It is our aim to make a difference to the lives of all MPN patients around Australia.

“We are grateful for the donations from supporters of the MPN cause and we are delighted to be able to contribute towards this unique project. We are excited to see what the outcomes of the study may reveal.”

The funds will directly support Dr. Steven Lane, of the Royal Brisbane Hospital in Queensland, Australia. He is a collaborator of Dr. Ann Mullally of Harvard.

About The Myeloproliferative Research Foundation

The MPN Research Foundation is fully dedicated to funding research into the myeloproliferative neoplasms, a rare group of blood cancers which include polycythemia vera, essential thrombocythemia and myelofibrosis. Founded in 2000 by a group of patients, the focus is to fund high innovation research that can expand our understanding of the MPNs and get us closer to a cure.

The Foundation’s Scientific Advisory Board works with the patient-led board of directors to utilize a rigorous selection process to ensure donations are allocated to the most innovative research projects. To date, the Foundation has awarded twelve million dollars for MPN research and has initiated a patient registry – myMPN – which is a platform that allows for people with ET, PV and MF to self-report their experience of living with an MPN.

To find out more go to www.mpnrf.org
For the patient registry: www.mympn.org
Twitter: MPN_RF
Facebook: https://www.facebook.com/MPNResearch/

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MPN Clinicians and Researchers meeting – Melbourne 27 April 2017

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The day prior to the MPNAE&I Patient Program in Melbourne, Australian MPN clinicians and researchers met with some US counterparts to share knowledge and ideas. In the photo below, Dr Ruben Mesa speaks  about the unmet needs of MPN patients, particularly those with Myelofibrosis. He discussed the role of Ruxolitinib, Interferon and clinical trials. He addressed the question of what would constitute failure of Ruxolitinib treatment, and when it might be appropriate to continue Ruxolitinib despite suboptimal symptom or spleen control, or hematological toxicity in this group of patients. Thanks again to Ann Brazeau and MPNAE&I for making this possible.

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