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Study FGCL-3019-079Trial of FG-3019, a Monoclonal Antibody to Connective Tissue Growth Factor, in Non-Ambulatory Subjects with Duchenne
Muscular DystrophyEwa Carrier, MD
Executive Director, Clinical DevelopmentFibrogen
CONFIDENTIAL
Disclosures
n I am full time employee of Fibrogenn Efficacy and safety of FG 3019 was not established in humans
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Outline
n Introduction of Fibrogenn Unmet need in DMDn Introduction of FG 3019n Preclinical datan Rationale/hypothesisn Protocol highlights
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Company background
n Fibrogen
l Founded in 1994
l Decades of experience in two unique and powerful areas of biology– Fibrosis biology– Hypoxia-inducible factor and prolyl hydroxylase biology
l FG-3019 – a novel anti-CTGF mAb for treating fibrotic disease– DMD non-ambulatory– Idiopathic pulmonary fibrosis– Pancreatic cancer
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FG-3019 Rationale and Pre-Clinical Background
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Unmet Need and Opportunities
n Key thought leaders agree that disease-modifying therapies (DMTs) which slow, stop, and ultimately reverse muscle degeneration are the most critical unmet need in DMD.
n However:l Current exon-skipping experimental treatments address less than one third of DMD patients.
l Even within the eligible sub-populations the individual responses may vary considerably.
n Based on an animal model of DMD, slowing or reversal of muscle fibrosis may improve muscle function
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FG-3019: mAb to Connective Tissue Growth Factor (CTGF)
§ Human monoclonal Antibody§ 10 Phase 1 and Phase 2 clinical trials completed or ongoing
§ 400+ adult patients treated with FG-3019§ Safety
§ With dosing > 2 years in some patients, no safety signals that might prevent further development of the drug
§ Proof of concept in pancreatic cancer and pulmonary fibrosis§ Dose related increased survival in pancreatic cancer§ Reversal of pulmonary fibrosis in some patients with IPF
§ Multiple potential indications in fibrotic diseases and cancers
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Connective Tissue Growth Factor - CTGF
n Glycoprotein secreted by many cell types
n Modulates the activities of growth factors and cytokines
n Regulates the interaction of cells with their environment
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Role of Fibrosis in DMD
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Fibrosis Arises from a Build-up of CTGF, Abnormal Cells and Collagen
Pessina 2014
CONFIDENTIAL
Blockade of CTGF with FG-3019 May Reverse Fibrosis
11J Clin Invest. 2007;; 117:524-9.
Excess CTGF
Normal Wound Healing Fibrosis
FibroGen
FG-3019
In mdx Mice, CTGF Blockade with FG-‐3019 Reduced Collagen, Improved Muscle Pathology and Improved Muscle Function
Morales 2013
FIBROGEN
In Mice and People With Lung Disease, FG-‐3019 Improved Diseased Lung and Improved Lung Function
Before FG-30192 weeks FG-3019
Week 16 Week 18
We Hope to Have the Same Effect in DMD Diseased Muscle
Mice with irradiated lungs
Lung histology
Lung CT
IPF patients treated with FG-‐301935% had stable/improved fibrosis
and improved lung function
Lung fu
nctio
n
Lung fibrosis
FIBROGEN
CONFIDENTIAL
Rationale for FG-3019 as a Treatment for DMD
n CTGF l Associated with fibrotic responses of many organsl Elevated in human DMD and in animal models of the disease
l Has been shown to induce a dystrophic phenotype in normal animals
n MDX mouse model of DMDl FG-3019 treatment attenuated tissue damage, fibrosis and loss of muscle strength, and increased exercise stamina
n Our hypothesis is that inhibition of fibrosis in DMD with FG-3019 maytherefore l Increase the contractile capacity of dystrophic musclesl Slow disease progression, improve patient quality of life and prolong survival
n The goal of this trial is to estimate FG-3019’s efficacy in non-ambulatory subjects with DMD.
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FG-3019-079Protocol Overview
Trial of FG-3019, a Monoclonal Antibody to Connective Tissue Growth Factor, in Non-
Ambulatory Subjects with Duchenne Muscular Dystrophy
CONFIDENTIAL
Trial Design
n Open label, single arm study of up to 22 non-ambulatory boys 12 years and older § Currently enrolling§ Each patient will receive FG 3019 by IV infusion every 2 weeks for up to 2 years
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Trial Objectives
n Objectives:
§ To evaluate safety, efficacy signals and assess pharmacokinetics (PK) and PD of FG-3019 in non-ambulatory boys with DMD aged 12 years and older
n Efficacy Endpoints:
§ Change in pulmonary function: forced vital capacity, maximum inspiratory flow, maximum expiratory pressure and peak expiratory flow, peak cough flow
§ Change in upper body muscle function tests: PUL, grip strength, pinch strength, Brooke score
§ Change in muscle fibrosis and/or fat by MRI imaging of biceps and heart
§ Changes in quality of life
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Key Inclusion Criteria
§ At least 12 years of age
§ Non-ambulatory;; wheelchair dependent for <5 years
§ Brooke Score for Arms and Shoulders ≤5
§ Able to perform spirometry
§ Able to undergo cardiac and extremity (upper arm) MRI
§ Percent predicted FVC ≥50
§ Estimated annual decline of FVC (% predicted) of ≥5% based upon at least 2 PFTs done in the previous 18 months, in addition to the screening FVC
§ Left ventricular ejection fraction >45% as determined by cardiac MRI at screening or within 3 months prior to Day 0
§ Stable regimen of heart failure cardiac medications for at least 3 months prior to screening
§ On a stable dose of corticosteroids for a minimum of 6 months
§ Adequate renal function, Adequate hematological function,
Adequate hepatic function
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Key Exclusion Criteria
§ Requires ≥16 hours continuous ventilation§ Anticipated back surgery within 1 year§ Severe uncontrolled heart disease § Arrhythmia requiring anti-arrhythmic therapy§ Hospitalization due to respiratory failure in the last 6 weeks§ Poorly controlled asthma or underlying lung disease such as bronchopulmonary dysplasia
§ BMI ≥40 kg/m2 or weight >117 kg§ Exposure to another investigational drug within 28 days prior to start of study treatment
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Participating Centers
§ Washington University in St. Louis, MO (recruiting) § Cincinnati Children’s in Cincinnati, OH (recruiting) § UCSF Benioff Children's Hospital in San Francisco, CA (recruiting)
§ UPMC Children's Hospital in Pittsburgh, PA (recruiting) § University of Iowa in Iowa City, IA (recruiting)
§ UCLA§ University of Southwest-Dallas§ Boston Children’s Hospital
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Additional Information
n For additional information regarding this study and sites please contact Gustavo Lorente (Fibrogen Clinical Program Manager)
n Fibrogen booth (Mission DMD)
[email protected]978-1441
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Acknowledgment
§ Extend our appreciation to our patients, their families and the DMD community
§ We would like to thank PPMD for the opportunity to participate in this webinar
§ Acknowledge the participation of our investigators
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