Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

RCSI iPATH collaboration identifies key biomarkers which may advance personalised treatment for people with haemophilia

03 December 2018

RCSI (Royal College of Surgeons in Ireland), Science Foundation Ireland (SFI) and Shire, in partnership with the Irish Haemophilia Society, today presented new data from the The Irish Personalised Approach to the Treatment of Haemophilia (iPATH) study which aims to advance research on personalised care for people with haemophilia A during the 60th American Society of Hematology (ASH) Annual Meeting in San Diego, California.

iPATH researchers have identified important biomarkers that influence bleeding risk in people with haemophilia.(1) Limiting the number of bleeds experienced by people with haemophilia is critically important, as bleeds left untreated can result in joint damage or other long-term issues. Personalised care will help reduce the number of bleeds and improve the health and quality of life of people with haemophilia.

Led by Professor James O’Donnell, Director of the Irish Centre for Vascular Biology at RCSI and Consultant Haematologist at the National Coagulation Centre, St James’s Hospital, Dublin, the iPATH study is investigating personalised treatment approaches by tailoring care based on the needs of individual patients. iPATH is supported by SFI and Shire, and is a partnership with the Irish Haemophilia Society.(2)

Using a database of more than 10 years of outcomes, together with patient responses to factor VIII replacement therapy (pharmacokinetic, PK, data) and whole genome sequencing,(3) iPATH aims to define how genetics and other biological markers impact patient responses to treatments.(4)

The standard of care treatment for haemophilia A currently is prophylaxis with recombinant factor VIII (rFVIII) replacement therapy, an approach designed to minimise bleeding episodes using a weight-based dosing strategy.(5) However, the length of time this medication works for (the half-life) varies markedly between individual patients, meaning some people continue to experience bleeding events even with prophylactic treatment.(1) iPATH researchers have found a link between patient’s blood type and half-life, with shorter half-life in blood group O patients.(1) In addition, a link was identified between older age and longer half-life.(1)

Importantly, the study also supports the feasibility of using limited, 2-sample pharmacokinetics (PK) profiling to capture accurate PK curves that can then be used to guide individualized, PK-guided prophylaxis.2 Traditionally, patients had to undergo 10 blood samples to measure half-life; now the same information is possible with 2 timed samples.(6,7) The approach to haemophilia care can now be improved by integrating FVIII PK to produce an individualized treatment regimen.(2)

References:

  1. Lavin, M et al. The Irish personalised approach to the treatment of haemophilia (iPATH) – determinant of inter-individual variation in FVIII pharmacokinetics, poster #1190. Presented at American Society of Hematology Annual Meeting 2018 on 1 December.
  2. Shire. Newsroom. Novel clinical study collaboration announced designed to improve clinical care for hemophilia patients through innovative personalized treatment. Accessible at https://www.shire.com/en/newsroom/2017/december/5c9igj. Accessed November 2018.
  3. SFI Strategic Partnership Programme. Expression of Interest Form. November 2013. Data on file.
  4. Irish Haemophilia Society. iPATH Research Project. December 2017. Available at: https://haemophilia.ie/about-haemophilia/haemophilia-worldwide/research/ipath-research-project/ Last accessed November 2018.
  5. Valentino, LA et. Al. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. Journal of Thrombosis and Haemostasis. 2012 Mar; 10(3): 359-367.
  6. U.S. Food and Drug Administration, Center for Biologic Evaluation and Research Office of Tissues and Advanced Therapies. myPKFiT for ADVATE Approval Letter BK170028, 18 December 2017.
  7. Lee M et al. 'Scientific and Standardization Committee Communication The Design and Analysis of Pharmacokinetic Studies of Coagulation Factors.' ISTH Website. https://c.ymcdn.com/sites/www.isth.org/resource/group/d4a6f49a-f4ec-450f-9e0f-7be9f0c2ab2e/official_communications/fviiipharmaco.pdf.