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imPACT – March 2021

Message from the Chair

Welcome to the first issue of imPACT in 2021. The year has started tumultuously for researchers, clinicians, people living with pulmonary fibrosis (PF) and their loved ones, with the halting of the Isabela clinical trials.

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Isabela 1 and 2 were the largest ever clinical trials in IPF, enrolling 1500 people globally. See the Trials Update section below for more information. Despite this setback we look forward to an even more productive year as we search for cures for PF.

Where does this leave the PF trials community? Whilst naturally very disappointing, it is only by conducting such large, well designed, well run, clinical trials that the field is able to move forward. Understanding that the

drug studied in the Isabela trials, the autotaxin inhibitor ziritaxestat, is not as effective as hoped, allows valuable resources to be reallocated to more promising drug targets. The PACT community is very proud to be able to contribute to this global effort. No doubt further analysis of the Isabela results, particularly in relevant participant subgroups, will provide further insight and guide the selection of novel drug treatments and the design of future studies.

We are now perhaps at a crossroads in PF drug development, with an increasing recognition of the importance of genetic mutations in disease pathogenesis meeting an unprecedented, multinational effort to find cures. It is likely that this new knowledge will inform trial design, with stratification for genetic mutations, or even trials designed for certain mutations just around the corner. If this topic is of interest, check out the first of a series of PACT/TSANZ/CRE-PF clinical trials webinars series in 2021.

Which neatly leads me to mention the soon to commence Telo-Scope study sponsored by The University of Queensland – perhaps the world’s first PF trial examining a potentially disease modifying drug. Again, could I encourage you to go to the Trials Update section below for more information.

I wish you well in 2021 and know you will enjoy this issue of imPACT, and particularly spending 5 minutes with Margaret Wilsher!

Professor Dan Chambers,

PACT Chair

Message from the CRE-PF

2021 has started at full speed for the CRE-PF team! Despite ongoing challenges of the global pandemic, we are in the fortunate position of being able to progress our strategic plan for the future of PF research in Australia.Image

In this issue of imPACT, I would like to highlight the great progress of the CRE-PF Translation EDucation and Support (TEDS) program. Led by Prof Anne Holland, TEDS is busy with various activities including publishing new educational resources for people living with PF, launching new initiatives to educate health professionals (look out for an ILD nurses expression of interest), and leading with consensus advice for COVID-19 vaccination.

Another ground-breaking recent TEDS achievement is a study identifying what research questions are most important to people living with PF, their caregivers, health professionals and researchers. There are many gaps in our knowledge about PF where research is needed. However, little has been known about what stakeholders consider the most important research questions that should be addressed as a priority.

recent study conducted by Anne Holland, Gabriella Tikellis and the TEDS team has identified the top 10 research priorities for PF across all stakeholders. We found that the top ranked priorities focused on medications to reverse scarring in the lungs (ranked 1st), improving lung function (ranked 2nd, 6th and 8th), interventions aimed at alleviating breathlessness and cough (ranked 5th and 7th), prevention of PF (ranked 3rd and 4th) and the best exercise programme for PF (ranked 10th). There was good consensus among patients/carers and health professionals/researchers on the top 10 priorities.

In short, we’ve shown that interventions aimed at preserving lung health and alleviating symptom burden are considered the most important priorities for PF. I expect that these findings will allow researchers, funders and policymakers to ensure that future research efforts are well aligned with stakeholder priorities. Our team looks forward to continued collaborative, strategic research to address these priorities. I encourage you to join us for the upcoming virtual CRE-PF Virtual Town Hall Meeting for a broader update on progress of the CRE-PF and future directions of PF research (see Upcoming Events of Interest section below).

Yours sincerely,

A/Prof Tamera Corte (CIA for CRE-PF)

Trials Update

It will be an exciting year for PACT, with multiple clinical trials commencing in 2021. In fact, we may well look back on 2021 as a pivotal year in PF clinical trials, with increasing interest in newer agents targeting more fundamental PF pathways. Our own homegrown Telo-Scope study will start in 2021, with funding from the federal government’s Medical Research Future Fund. Telo-Scope will study the effect of the testosterone analogue danazol or placebo in people with PF related to telomere shortening. Telomeres are the protective caps on the end of chromosomes which protect the genome from damage during cell replication. It is now recognised that mutations in telomere maintenance genes are responsible for a substantial minority of PF. Studies from the field of haematology suggest that male sex steroids are able to enhance telomere maintenance, sparking the world-first Telo-Scope study. Telo-Scope will be recruiting at sites all over Australia.

As all Isabela trial participants will be aware, this, the largest ever clinical trial in IPF was halted on February 11th. Galapagos and Gilead, the trial sponsors, developed ziritaxestat, a first-in-class autotaxin inhibitor following encouraging phase 2 trial results. All trials involving ziritaxestat, including the Isabela trials, have been halted on the advice of the independent, unblinded, data safety monitoring committee. Following their regular review of unblinded data, the Committee concluded that ziritaxestat’s benefit-risk profile no longer supported the continuation of the studies, a huge blow to all involved. Can I personally thank all participants who gave up their time to participate in the Isabela studies.

Watch this space for new trials of oral, inhaled and intravenous investigational agents from Sponsors like Bristol Myers Squibb, Algernon, Avalyn, Galecto, FibroGen, Boehringer-Ingelheim and Roche, all due to commence recruitment in 2021.

Introducing the Consumer Advisory Group

The PACT Consumer Advisory Group (CAG) consists of seven people, six of whom are at various stages along the PF journey since diagnosis, plus one caregiver. The group is chaired by Professor Anne Holland and convened by Dr Alison Hey-Cunningham.

Since forming in June 2020, the CAG has convened via Zoom approximately monthly. We began by clarifying our terms of reference, which are primarily to provide feedback from a research participant/consumer perspective on proposed clinical trials and to share our views on current and future research needs on the basis of our experiences of living with PF. We also undertook some initial training on processes involved in developing and evaluating clinical trials.

In the latter part of 2020 CAG reviewed two upcoming PF research studies, the first examining the impact of COVID-19 on access to treatment and support for people with PF and the second investigating a medication to preserve telomere length in PF patients. The group enthusiastically provided constructive and detailed feedback on both studies. Feedback included aspects of the participant information that could be written more clearly, suggested refinements to the questionnaire items, and for the second study, identified facets of the procedures that were potentially daunting and might benefit from providing additional participant support. This feedback was collated and provided to the study investigators for their consideration.

As individuals profoundly impacted by PF, we are united in our vision for research to ultimately develop a cure for this disease. We are also strongly committed to promoting awareness of PF amongst medical and allied health professionals and throughout the general community. This need is becoming even more apparent due to the likely increase in PF-related conditions as an aftermath of the COVID-19 pandemic.

Grants

Applications for the second annual PACT Grant-in-Aid closed last month and are currently under review. We are excited to support investigator led pulmonary fibrosis clinical research and look forward to announcing the award recipient at TSANZSRS in May.

Other current grant opportunities relevant to PF clinical research and trials:

  1. MRFF 2020 Clinician Researchers Applied Research in Health Grant – To support medical research and innovation projects that validate and implement new approaches for improving the quality and consistency of patient care. Closing 12 April 2021.
  1. NHMRC Synergy Grants – To support outstanding multidisciplinary teams of investigators to work together to answer major questions that cannot be answered by a single investigator. Closing 21 April 2021.
  1. NHMRC Ideas Grants – To support innovative research projects addressing a specific question that is innovative and creative in any area of health and medical research from discovery to implementation. Closing 5 May 2021.
  1. MRFF International Clinical Trial Collaborations Grant – For new clinical trials in Australia in collaboration with international counterparts. Closing 16 Fen 2022.

Upcoming Events of Interest

In collaboration with TSANZ and the CRE-PF, PACT is excited to announce a pulmonary fibrosis clinical trials webinar series in 2021. Our first webinar “New Drugs for pulmonary fibrosis – are there any blockbusters around the corner” will catch health professionals up on the latest in drug development and clinical trials in PF. It will take place on Tuesday 30 March 12-1pm AEDT. Register here.

The CRE-PF monthly Australasian Pulmonary Fibrosis Virtual Research Meetings promoting collaboration and discussion amongst researchers interested in PF continue in 2021. We encourage you to join us for a Virtual Town Hall Meeting “Future Directions of PF Research” on Friday 23 April 12-1pm AEST. Contact Kate Christian on create@cre-pf.org.au to find out more about the program and how to join.

The TSANZSRS Annual Scientific Meeting will be a fully virtual event 1-2 May. The OLIV SIG (Orphan Lung Diseases, Lung Transplant, Interstitial Lung Disease and Pulmonary Vascular Disease Special Interest Group) day is on 18 May.

Membership

The PACT network welcomes new members across all aspects of PF research, care and life with the condition.

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Five Minutes with a Pulmonary Fibrosis Researcher Prof Margaret Wilsher

Prof Wilsher, from Auckland City Hospital and The University of Auckland, sat down with the PACT team to talk about her career in PF, including how it started, her research interests and how she’s dealt with challenges along the way.

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