Preparing for genetic N-of-1 treatments of patients with ultra-rare mutations

IRDiRC - Preparing for genetic N-of-1 treatments of patients with ultra-rare mutations

Introduction

The N-of-1+ therapy approach is transforming the drug development landscape and has the potential to facilitate treatment of patients with ultra-rare diseases for whom no previous treatment has been developed. However, while the development of therapies specific to very few patients has a lot of promise, the largest challenge faced by these initiatives is that the drug development, regulatory frameworks and reimbursement systems were not designed for N-of-1+.

Objectives

The overall objective of this Task Force is to connect different N-of-1+ efforts to reduce duplication, achieve global consensus and create a roadmap towards development and implementation of N-of-1+ treatment.

  1. To produce a reference document summarizing the current state-of-the art, to raise awareness of the N-of-1+ concepts and challenges with all stakeholders
  2. To identify the major challenges hampering N-of-1+ therapy development and timely patient access, in order to allow for development of proposed solutions and create a better opportunity for strategic planning and delivery of N-of-1 therapies

Timeline

Assembly of the Task Force Group in Q1, 2023;

In-person workshop took place on 2-3 November in Barcelona, Spain.

Members

  • Annemieke Aartsma-Rus – Leiden University Medical Center, The Netherlands (Co-Chair)
  • Anneliene Jonker – University of Twente & Duchenne Parent Project, The Netherlands (Co-Chair)
  • Daniel O’Connor – The Association of the British Pharmaceutical Industry (ABPI), UK (Co-Chair)
  • PJ Brooks – NCATS/NIH, USA
  • Timothy Yu – Harvard Medical School, USA
  • Erika Augustine – The Johns Hopkins University School of Medicine, USA
  • Adam Jaffe – UNSW Sydney, Australia
  • Alison Bateman-House – NYU Grossman School of Medicine, USA
  • Julie Douville – n-Lorem Foundation, Canada
  • David Dimmock – Creyon Bio, USA
  • Larissa Lapteva – FDA, USA
  • Marjon Pasmooij – Dutch Medicines Evaluation Board, The Netherlands
  • Matthis Synofzik – Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tubingen, Germany
  • Oxana Iliach – Certara, Canada
  • Ralf-Dieter Hilgers – RWTH Aachen University, Germany
  • Virginie Hivert – EURORDIS, France
  • Gareth Baynam – Rare Care Centre/Perth Children’s Hospital, Australia
  • Holm Graessner – European Reference Network for Rare Neurological Diseases (ERN-RND), Germany
  • James Davies – Weatherall Institute of Molecular Medicine, Oxford University, UK
  • Jill Morris – NINDS/NIH, USA
  • Rich Horgan – Cure Rare Disease, Inc., USA
  • Shruti Mitkus – Global Genes, USA

Educational Resources

List of curated resources is available at the following link: https://irdirc.org/wp-content/uploads/2023/12/N-of-1-Education-Resources-1-1.pdf

Publications

The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap. Anneliene H Jonker, Elena-Alexandra Tataru, Holm Graessner, David Dimmock, Adam Jaffe, Gareth Baynam, James Davies, Shruti Mitkus, Oxana Iliach, Rich Horgan, Erika F Augustine, Alison Bateman-House, Anna Maria Gerdina Pasmooij, Tim Yu, Matthis Synofzik, Julie Douville, Larissa Lapteva, Philip John Brooks, Daniel O’Connor, Annemieke Aartsma-Rus. Nat Rev Drug Discov. 2024. Access the paper here.