BBIO-Infigratinib-ESPE 2026-Longer Term Results

Marie-Eve Robinson1, Melita Irving2, Ravi Savarirayan3, Paul Arundel4, Josep Maria de Bergua5, Philippe M. Campeau6, Thomas Edouard7, Svein Fredwall8, Paul Harmatz9, Henrik Irgens10, Jeannette Goh11, Antonio Leiva-Gea12, Helen McDevitt13, Roberta Onesimo14, John Phillips15, Mariana del Pino16, Massimiliano Rossi17, Kim Davis18, Lixin Zhang18, Diana Davydov18, Xinyuan Duan18, David van Veenhuyzen18, Julie Hoover-Fong19

1Shriners Hospital for Children Canada, McGill University, Montreal, Canada; 2Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; 3Murdoch Children's Research Institute, Parkville, Australia; 4Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom;

5MIKS Hospital, Vitoria-Gasteiz, Spain; 6Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada; 7Children's Hospital, Toulouse University Hospital, Toulouse, France; 8Oslo University Hospital, Oslo, Norway; 9UCSF Benioff Children's Hospital Oakland, Oakland, United States of America;

10Haukeland University Hospital, Bergen, Norway, 11KK Women's and Children's Hospital, Singapore, Singapore; 12Hospital Universitario Virgen de la Victoria, Malaga, Spain; 13NHS Greater Glasgow and Clyde, Glasgow, United Kingdom; 14Fondazione Policlinico A Gemelli IRCCS,

Catholic University of Sacred Heart, Rome, Italy; 15Vanderbilt Health, Nashville, United States of America; 16Hospital de Pediatría Garrahan, Buenos Aires, Argentina; 17Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon, France; 18BridgeBio Pharma, San Francisco, United States of America;

19Johns Hopkins University, Baltimore, United States of America

BACKGROUND

• Infigratinib is an oral FGFR1-3 tyrosine kinase inhibitor under investigation as a treatment for achondroplasia (ACH), an FGFR3-driven skeletal dysplasia characterized by disproportionate short stature1,2

• The phase 2 PROPEL 2 trial provided clinical proof-of-concept for the 0.25 mg/kg/day dosing of infigratinib for children with ACH1

• Subsequently, the efficacy and safety of infigratinib 0.25 mg/kg/day were demonstrated in the pivotal, randomized, double-blind, placebo-controlled PROPEL 3 trial in children aged 3 to <18 years with ACH2

  • The primary endpoint was met, with infigratinib demonstrating a significant increase from baseline at week 52 in annualized height velocity compared with placebo (difference in least-squares mean change from baseline [CFBL]: 1.74 cm/year, p<0.0001; difference in observed mean CFBL: 2.10 cm/year)

  • Treatment with infigratinib also resulted in a significant increase from baseline at week 52 in height z-score compared with placebo (0.32, p<0.0001) and a trend toward improvement in upper-to-lower body segment ratio, which reached nominal significance in children aged 3 to <8 years

• Here, we report preliminary findings of the longer-term efficacy and safety of infigratinib in children with ACH across the PROPEL clinical program

  METHODS

• Mean height z-score continued to numerically increase at each successive annual visit through Year 3

  (Figure 2)

  Figure 2. Height z-score relative to CLARITY

  1.28

  1.6

  0.71

  0.50

  0.09

  1.4

  Mean height z-score

  1.2

  1.0

  0.8

  0.6

  0.4

  0.2

  0

  -0.2

  Baseline Year 1

  Visit

  Year 2 Year 3

• The PROPEL clinical program in children aged 3 years and older with ACH comprises the observational

  No. of participants 94 94

  22 11

  run-in PROPEL study, the phase 2 PROPEL 2 study, the phase 3 PROPEL 3 study, and the open-label extension PROPEL OLE study (Figure 1)

  Figure 1. PROPEL clinical program design

  Mean CFBL in height z-score 0.41 0.66 0.92

  Error bars indicate the standard error.

• Mean upper-to-lower body segment ratio numerically decreased across annual visits through Year 3 (Figure 3)

  Figure 3. Upper-to-lower body segment ratio

  2.07

  Mean upper-to-lower body segment ratio

  2.2

  2.00

  1.98

  1.84

  2.1

  2.0

  1.9

  PROPEL:

  Observational run-in study

  Participants: Children aged 2.5 to <17 years with confirmed diagnosis of achondroplasia

  Observation

  PROPEL 2:

  Open-label dose-escalation and dose-expansion phase 2 study

  Participants: Children aged 3 to <11 years with confirmed diagnosis of achondroplasia

  Infigratinib

  0.25 mg/kg/day Extended treatment period

  Infigratinib

  0.128 mg/kg/day Extended treatment period

  Infigratinib

  0.064 mg/kg/day Extended treatment period

  Infigratinib

  0.032 mg/kg/day Extended treatment period

  Infigratinib

  0.016 mg/kg/day Extended treatment period

  PROPEL OLE:

  Open-label extension study

  Participants: Children aged 3 to <18 years who completed PROPEL 2 or PROPEL 3, or who are treatment-naïve and

  completed ≥6 months in PROPEL

  Infigratinib

  0.25 mg/kg/day

  Children are followed for a minimum of 6 months

  PROPEL 3:

  Randomized, double-blind, placebo-controlled phase 3 study

  Participants: Children aged 3 to <18 years with confirmed diagnosis of achondroplasia

  Infigratinib 0.25 mg/kg/day

  2:1

  Placebo

  Followed on treatment until adult height is reached

  1.8

  1.7

  Baseline Year 1 Year 2 Year 3

  Visit

  No. of participants 94 94 22 11

• Eligible participants from PROPEL, PROPEL 2, and PROPEL 3 rolled over to PROPEL OLE to receive infigratinib until adult height is reached

• These analyses focused on participants of the PROPEL clinical program who initiated treatment with infigratinib at the 0.25 mg/kg/day dose

  Pooled efficacy population

  • The pooled efficacy analysis included participants who received infigratinib 0.25 mg/kg/day for at least one year

    Upper-to-lower body segment ratio = Sitting height

    Standing height - Sitting height

    Rhizomelic shortening of the limbs relative to the trunk results in the upper-to-lower body segment ratio to be approximately 2.0 in children with ACH, while average stature populations typically reach a ratio of 1.04,5

    
    
    

    Sitting height

    Standing height

    Upper segment

    • The primary endpoint was absolute value and CFBL in height z-score relative to CLARITY3 reference data, and a key secondary endpoint was absolute value and CFBL in upper-to-lower body segment ratio

      Lower segment

      Safety population

  • The safety analysis included participants who received at least one dose of infigratinib in PROPEL OLE

    • Safety data reported here are all events that had an onset after the first dose of infigratinib on PROPEL OLE

      RESULTS

      Pooled efficacy population

• At data cutoff of 07-November-2025, a total of 94 participants (23 from PROPEL 2 and 71 from PROPEL 3) were included in the pooled efficacy population (Table 1)

• Median (range) duration of treatment among participants included in the pooled efficacy population was 433 (353-1236) days

  Table 1. Characteristics of pooled efficacy population at baseline of PROPEL 2 or PROPEL 3

  Characteristic	Pooled efficacy population (n=94)
  Age at first dose in PROPEL 2 or PROPEL 3
  Mean (SD), years	7.7 (2.6)
  Median (range), years	7.3 (3.7-14.4)
  Distribution, n (%)
  3 to <8 years	56 (60)
  8 to <18 years	38 (40)
  Sex, n (%)
  Female	44 (47)
  Male	50 (53)
  Race,* n (%)
  Asian	16 (17)
  Black or African American	4 (4)
  White	60 (64)
  Multiple	6 (6)

  *Not reported (n=8). SD, standard deviation.

  REFERENCES: 1. Savarirayan R, et al. Oral Infigratinib Therapy in Children with Achondroplasia. N Engl J Med. 2025;392(9):865-874. 2. Savarirayan R, et al. Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia. N Engl J Med. 2026. Online ahead of print. 3. Hoover-Fong JE, et al. Growth in achondroplasia including stature, weight, weight-for-height and head circumference from CLARITY: achondroplasia natural history study-a multi-center retrospective cohort study of achondroplasia in the US. Orphanet J Rare Dis. 2021;16(1):522. 4. Hoover-Fong JE, et al. Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height. Am J Clin Nutr. 2008;88(2):364-71. 5. Savarirayan R, et al. Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study. Genet Med. 2022;24(12):2444-2452.

  FUNDING: These studies were sponsored by BridgeBio Pharma, Inc., San Francisco, CA, US.

  ACKNOWLEDGEMENTS: The authors would like to thank all the children and families, and all the investigators and study teams, who participated in the PROPEL clinical program.

  PRESENTING AUTHOR DISCLOSURES: Melita Irving has received honoraria and travel-associated expenses from BridgeBio Pharma, BioMarin, Ascendis Pharma, and Tyra Biosciences.

  Mean CFBL in upper-to-lower body segment ratio -0.07 -0.15 -0.15

  Error bars indicate the standard error.

  Safety population

• At data cutoff of 07-November-2025, a total of 146 participants who rolled over to PROPEL OLE (33 from PROPEL, 24 from PROPEL 2, and 89 from PROPEL 3) were included in the safety population (Table 2)

• Median (range) duration of treatment in PROPEL OLE among participants included in the safety population was 109 (2-725) days

  Table 2. Characteristics of safety population at baseline of PROPEL OLE

  Characteristic	Safety population (n=146)
  Age at baseline of PROPEL OLE
  Mean (SD), years	8.6 (2.6)
  Median (range), years	8.2 (4.0-15.9)
  Distribution, n (%)
  3 to <8 years	68 (47)
  8 to <18 years	78 (53)
  Sex, n (%)
  Female	61 (42)
  Male	85 (58)
  Race,* n (%)
  Asian	23 (16)
  Black or African American	3 (2)
  White	101 (69)
  Other	14 (10)

  *Not reported (n=5).

• Infigratinib continued to be well tolerated in PROPEL OLE, with infrequent grade 3 and serious treatment-emergent adverse events (TEAEs) and no grade 4 TEAEs or TEAEs leading to treatment discontinuation (Table 3)

  Table 3. Summary of adverse events in PROPEL OLE

  Category, n (%)	Safety population (n=146)
  Any TEAE	102 (70)
  Treatment-related TEAE*	5 (3)
  Grade 3 TEAE†	5 (3)
  Treatment-related grade 3 TEAE	0
  Grade 4 TEAE	0
  Treatment-related grade 4 TEAE	0
  Serious TEAE‡	3 (2)
  Treatment-related serious TEAE	0
  TEAE leading to dose modification§	4 (3)
  TEAE leading to dose interruption	3 (2)
  TEAE leading to dose reduction	2 (1)
  TEAE leading to treatment discontinuation	0
  TEAE leading to death	0

  Adverse events include all events that had an onset after the first dose of infigratinib on PROPEL OLE and before the latest dose plus 30 days.

  *Treatment-related TEAEs reported in this study included: hyperphosphatemia (n=2), arthralgia (n=1), pain in extremity (n=1), and rash erythematous (n=1). † Grade 3 TEAEs reported in this study included: adenoidal hypertrophy (n=1), delirium febrile (n=1), dental caries (n=1), gastritis (n=1), and meniscus injury (n=1). ‡Serious TEAEs reported in this study represent three of the same grade 3 TEAEs noted in the previous footnote: adenoidal hypertrophy (n=1), delirium febrile (n=1), and gastritis (n=1). §Participants may be included in more than one dose modification category.

  CONCLUSIONS

• Treatment with oral infigratinib 0.25 mg/kg/day led to sustained numerical improvements in height z-score and upper-to-lower body segment ratio in children with ACH; however, the small sample sizes at Years 2 and 3 suggest they should be interpreted with appropriate caution

• The safety profile of infigratinib remained consistent with previously reported findings, with no new safety concerns identified in PROPEL OLE

• Continued follow-up in PROPEL OLE will further characterize the long-term treatment effects and expand the safety experience with infigratinib

Presented at the 64th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE 2026), September 8-10, Marseille, France