Slide 1: Treatment landscape and unmet need in Achondroplasia
Treatment landscape and unmet need in Achondroplasia Dr. Melita Irving Consultant in Clinical Genetics, Guy’s and St Thomas’ NHS Trust, London UK Investigator across the achondroplasia clinical trial programmes
Slide 2: Disclosures
Disclosures Dr Irving has received honoraria for consultancy, scientific advisory board and speaker services from: • QED/Bridge Bio • BioMarin • Ascendis Pharma • Sanofi • Innoskel • Ipsen • Alexion • Kyowa Kirin • NovoNordisk
Slide 3: Achondroplasia is the most common cause of disproportionate short stature
Achondroplasia is the most common cause of disproportionate short stature Thanks to Dr Wil McKenzie
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Slide 5: Multisystem complications as a consequence of the secondary abnormal bone formation
Multisystem complications as a consequence of the secondary abnormal bone formation
Slide 6: MH data from PROPEL highlight the significant complications experienced during infancy and childhood
MH data from PROPEL highlight the significant complications experienced during infancy and childhood Surgical and medical procedures occurring in≥1 subject • A total of 58 children (67.4%) had undergone surgical or medical procedures, with a mean of 2.9 procedures per individual (1–11 interventions
Slide 7: Infections, Respiratory and Musculoskeletal disorders
Infections, Respiratory and Musculoskeletal disorders • A history of infections and infestations was reported in 46 children (53.5%). The most common of these were ear infections (n=43; 50.0%) • A history of respiratory disorders was reported in 40 children (46.5%). The most common was sleep apnea (
Slide 8: Other conditions/events reported as medical history
Other conditions/events reported as medical history • Ear and labyrinth disorders were found in 15 children Ear and labyrinth disorders No. of subjects (%)* Hearing loss 6 (7.0) (17.4%), all of whom presented hearing impairment Conductive hearing loss 5 (5.8) Hypoacusis 4 (4.7) Middle ear effusion 1
Slide 9: HRQOL tools and height Z-score
HRQOL tools and height Z-score
Slide 10: Complications of achondroplasia (%) in childhood
Box2 Complications of achondroplasia (%) in childhood > Neurological > Foramen magnum compression (5—10%) > Craniocervical instability (very rare) > Symptomatic hydrocephalus (6%) » Orthopaedic > Progressive, unresolving thoracolumbar kyphosis > Decreased range of movement, elbows and hips >» Tibial
Slide 11: Achondroplasia is a genetic disorder of FGFR3: de novo event or inherited from a parent with Ach
Achondroplasia is a genetic disorder of FGFR3: de novo event or inherited from a parent with Ach
Slide 12: FGFR3 acts to regulate the growth plate through inhibition of other growth signals
FGFR3 acts to regulate the growth plate through inhibition of other growth signals Immature cartilage cells Bone formation
Slide 13: Activating mutation in FGFR3 - G380R
Activating mutation in FGFR3 - G380R
Slide 14: Activating mutation in FGFR3 - G380R
Activating mutation in FGFR3 - G380R
Slide 15: Summary
Summary • Achondroplasia is a medical condition with lifelong multisystem complications • It is secondary to abnormal bone growth, the consequence of a recurrent genetic variant • Interventions to attempt to restore skeletal growth present encouraging opportunities to improve quality of life and sig