June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
A patient-driven, multi-stakeholder, collaborative approach to address IRD endpoint challenges: the RDH12 example
Author Affiliations & Notes
  • Silvia Cerolini
    Eyes on the Future, United Kingdom
  • Jean Bennett
    University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Bart Peter Leroy
    Universiteit Gent, Gent, Belgium
    University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Tomas S Aleman
    University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Avril Daly
    Retina International, Ireland
  • Todd Durham
    Foundation Fighting Blindness Inc, Columbia, Maryland, United States
  • Courtney Coates
    Hope in Focus, Connecticut, United States
  • Mathew Pletcher
    RDH12 Fund for Sight, Massachusetts, United States
  • Sue Lacey
    Astraea Medical Consulting, United Kingdom
  • Footnotes
    Commercial Relationships   Silvia Cerolini ProQR, Code C (Consultant/Contractor), Sanofi, Code E (Employment); Jean Bennett Frontera, Akouos, Spark Therapeutics, Sparing Vision, Regenx Bio, Code C (Consultant/Contractor), Gyroscope, Accugen, Code F (Financial Support), Opus Genetics, Code O (Owner), U Penn, Code P (Patent); Bart Leroy 4DMT, AAVantgardeBio, Akouos, Asthena Therapeutics, Bayer, Biogen, GenSight Biologics, Iveric Bio, Janssen, Novartis, Opus Genetics, Oxurion, ProQr Therapeutics, RegenxBio, Santen, Spark Therapeutics, Transine Therapeutics, Vedere Bio, ViGeneron, Code C (Consultant/Contractor), Biogen, GenSight Biologics, Janssen, MeiraGTX, Novartis, ProQR Therapeutics, Code F (Financial Support), GenSight Biologics, Iveric Bio, Novartis, ProQR Therapeutics, Spark Therapeutics , Code R (Recipient); Tomas Aleman U Penn, Code P (Patent); Avril Daly None; Todd Durham None; Courtney Coates None; Mathew Pletcher Ray Therapeutics, Code C (Consultant/Contractor), Kisbee Therapeutics, Code E (Employment); Sue Lacey Adverum, Nanoscope, Code C (Consultant/Contractor), Adverum, Code I (Personal Financial Interest)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 795. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Silvia Cerolini, Jean Bennett, Bart Peter Leroy, Tomas S Aleman, Avril Daly, Todd Durham, Courtney Coates, Mathew Pletcher, Sue Lacey; A patient-driven, multi-stakeholder, collaborative approach to address IRD endpoint challenges: the RDH12 example. Invest. Ophthalmol. Vis. Sci. 2023;64(8):795.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : To illustrate how a patient-driven, multi-stakeholder approach to address IRD endpoint challenges can be an efficient model to advance efforts to bring innovative therapies to patients.

Inherited Retinal Diseases (IRDs) are caused by mutations in 270+ genes and represent a significant unmet need. After the first ocular gene therapy approval in 2017 for RPE65-IRD, there have been no subsequent approvals, due to challenges in trial design and endpoints. RDH12-IRD is an early onset, severe IRD leading to near total blindness by early 20s. Gene therapy trials are anticipated within 18 months.

Methods : The 2nd Global RDH12 Scientific Workshop in Baltimore, MD, USA, hosted in November 2022 by the RDH12 Global Alliance in partnership with Retina International, FFB and Hope in Focus, catalyzed constructive discussion to accelerate treatments for RDH12 patients. Attendees included 5 key groups: scientific, clinical and industry experts, patients’ representatives, and regulatory agencies (FDA and EMA).
A structured, moderated, albeit open discussion tackled recent natural history learning and failings from other IRD trials as well specific challenges in outcome measures (OM) covering traditional and emerging technologies.

Results : The workshop led to important shared considerations for RDH12-IRD with relevance across all IRDs:
-Stability of visual function has extreme value for patients. Even retention of light perception is important and considered a meaningful OM from regulators due to its absolute value
-Limitations of traditional OM, e.g. visual acuity, were recognized
-Objective measures of the slope of photoreceptor loss by imaging over a defined time-period (1-2 years) is considered a valid OM by regulators, even in absence of functional change
- A VR mobility maze is an alternative to the physical maze and is in the final stages of validation
-Full-field stimulus testing (FST) is yet to be accepted by regulatory bodies as a primary outcome
-While no PROs are currently accepted as primary endpoint, an opportunity exists for novel performance-based tests measuring improvements in patients’ daily living

Conclusions : A patient-driven, multi-stakeholder, collaborative workshop is an innovative model to drive a focused conversation to optimize the chances of trial success and advance the field. It serves as a model of how patients are effective partners on the path to successful treatments.
.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×