BridgeBio Pharma : BBIO – BBP-418 – MDA 2024 – Development of PROMIS Tool

Development of Pediatric and Adult

LGMD2I/R9 Disease-Specific Physical Function

Questionnaires Using PROMIS Item Banks

Divya B. Reddy, MD1, Beth Leiro1, Katherine Mathews, MD, FAAN2, and John Vissing, MD, DMSci3

1. ML Bio Solutions, a BridgeBio company, Palo Alto, CA
2. University of Iowa Carver College of Medicine, Iowa City, IA
3. Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, DK

Introduction

Visualization of Process

Limb girdle muscular dystrophy type 2I, R9 FKRP-related (LGMD2I/R9) is caused by bi-allelic partial loss-of-function of the fukutin-related protein (FKRP) gene, resulting in hypoglycosylation of α-dystroglycan (αDG) and progressive muscle damage.

• FORTIFY (NCT05775848) is a Phase 3 multinational double-blind placebo- controlled study enrolling individuals aged 12-60 years with LGMD2I/R9.
• BBP-418is an oral substrate intended to saturate the partially functional FKRP enzyme, driving increased glycosylation of αDG, and potentially ameliorating the root cause of LGMD2I/R9.

Although physical function deficits are well documented in LGMD2I/R9, there are no disease-specificpatient-reported outcomes (PROs) that assess the impact of these deficits on daily life. Our aim was to develop disease- specific physical function PROs to assess the impact of impaired physical function in individuals with LGMD2I/R9.

Methods

Began with PROMIS Item Bank Items

Filtered them through

• Selection Criteria

Pediatric Adult

50 165

Items*Items**

Proximal Weakness

ACTIVLIM

Patient Experience and

Patient Advocate Endorsement

Items from the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric and Adult Physical Function Item Banks were selected to create custom Physical Function PROMIS questionnaires. The items were methodically chosen to include LGMD2I/R9 disease concepts of interest, with careful consideration to ensure that the selection of items was informed by a variety of sources and covered a broad range of physical function.

Item selection was informed by the following criteria:

Proximal Weakness: The impact of proximal weakness on mobility and activities of daily living (ADL) was assessed, and items relying on proximal strength were selected.

Activity Limitations Questionnaire (ACTIVLIM): This PRO assesses activity limitations in patients with neuromuscular disorders and items on the PROMIS item banks that overlapped with ACTIVLIM items were selected.

Patient Experience and Patient Advocate Endorsement: We included information from a patient survey sponsored by ML Bio to gather insights from the LGMD2I/R9 patient community about disease burden and transcripts from patient day where patients shared their experiences of living with LGMD2I/ R9. In addition, a roundtable for patient advocates was convened during which all of the selected items were endorsed. The patient advocate roundtable also highlighted additional challenges in activities of daily living, indicating that further research in this area is needed to explore common ADL related difficulties more fully in the LGMD2I/R9 patient population.

Key Opinion Leaders (KOL) Endorsement: A round table was convened with LGMD2I/R9 physician specialists for guidance and endorsement of selected items.

Conclusions

LGMD2I/R9 specific physical function questionnaires for adults and children were created using the PROMIS Item Banks. Validation studies and correlation of PRO data with standardized performance measures are planned. If validated, this PRO can be a useful addition to clinical trials, such as FORTIFY.

KOL Endorsement

Concluded with LGMD2I/R9	15	22
specific physical function items	Items	Items

				14%
				Items
51%				Substantiated
			by 2/4 Selection
				Criteria
Items
Substantiated	35%
by 4/4 Selection
Criteria
Items
				Substantiated
				by 3/4 Selection
				Criteria

Acknowledgements

The authors would like to thank the individuals with LGMD2I/R9 and their families who provided their perspectives on living with LGMD2I/R9, as well as The Speak Foundation, CureLGMD2i Foundation and the LGMD Awareness Foundation for participating in a patient advocate round table.

The authors would also like to thank the ML Bio Solutions PROMIS Working Group, including Tricia Blankenbiller, Lindsay Reklis, Tasha Farmer, and Anne Lee. Finally, the authors appreciate the contributions of Cybele Gouverneur and Mallory Harden, who supported the patient advocate roundtable and poster development, respectively.

*PROMIS Pediatric Item Bank Mobility, PROMIS Pediatric Item Bank Upper Extremity **PROMIS Physical Function Item Bank

Disclosures: John Vissing has acted as consultant for Amicus Therapeutics, argenx BVBA, Arvinas, Atamyo Therapeutics, Biogen, Dyne Therapeutics, Fulcrum Therapeutics, Horizon Therapeutics, Lupin, ML Bio Solutions, Regeneron, Roche, Sanofi Genzyme, Sarepta Therapeutics, and UCB Biopharma SPRL, and has received research grants, travel support, and/or speaker fees from Alexion, AstraZeneca Rare Disease, Edgewise Therapeutics, Fulcrum Therapeutics, Horizon Therapeutics, Sanofi Genzyme, and UCB Biopharma SPRL. Kathy Mathews has received research funding from NIH, CDC, and FARA. She is a consultant for Sarepta Therapeutics and Edgewise Therapeutics (no personal compensation). She is the site principal investigator for studies sponsored by Sarepta Therapeutics, Edgewise Therapeutics, PTC, Italfarmaco, Reata, Pfizer, Capricor, Fibrogen, Biogen, Biohaven, Scholar Rock, AMO, ML Bio, Ask Bio, and Genethon. Divya B. Reddy is an employee of ML Bio Solutions, a BridgeBio company, and may have equity compensation packages as part of such employment. Beth Leiro is a consultant of ML Bio Solutions, a BridgeBio company.

PediatricAdult

QuestionnaireQuestionnaire

Resulting

LGMD2I/R9 Specific

Questionnaires