Ari Gershman, DO - PFF Summit · Paula Belloni, Ari Gershman, Andrew Ackrill, Ramona Doyle, Laurie...
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Transcript of Ari Gershman, DO - PFF Summit · Paula Belloni, Ari Gershman, Andrew Ackrill, Ramona Doyle, Laurie...
Saturday, December 7, 2013 Overview of Lebrikizumab Program in
Idiopathic Pulmonary Fibrosis (RIFF Study) Ari Gershman, DO
www.pffsummit.org | www.pulmonaryfibrosis.org
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Overview of lebrikizumab program in Idiopathic Pulmonary Fibrosis (RIFF Study) Paula Belloni, Ari Gershman, Andrew Ackrill, Ramona Doyle, Laurie Katugampola, Janusz Kaminski
Ari Gershman, DO Medical Director, Genentech, Inc. South San Francisco, CA
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Rationale for targeting IL-13 in IPF patients
Lebrikizumab:
• Novel, humanized, Mab with high specificity and affinity for IL-13
• Inhibits IL-13 functions with high potency
• Prevents formation of the active heterodimer receptor, blocking downstream signalling
• Monthly SC dosing via a prefilled syringe
IL-4Rα
IL-13Rα1
STAT-6 signaling: *IPF-Epi/EMT transition,
myofibroblast activation, collagen and matricellular protein, profibrotic
growth factors TGFb and PDGF M2 activations
IL-13 Role of IL-13 in fibrosis: • Disruption of IL-13 signaling in
mice reduces fibrosis
• Transgenic over-expression of IL-13 in lung induces fibrosis in mice
• IL-13 levels correlate inversely with disease severity (FVC and Dlco)
• IL-13 biomarkers shown to be elevated and inversely correlated with severity/prognosis
– Periostin (FVC and Dlco) – CCL18 (FVC and mortality)
IL-13 is a potent inducer of fibrogenic responses in vitro and in vivo
Park et al. 2009, Okamoto et al. 2011, Prasse et al. 2007,2009
RIFF - Study Design Event driven trial
Lebrikizumab (N=125)
Placebo (N=125)
Week 0 Week 52
18wk
≤4-wks
≥ 75 PFS events + LPE @ Week 52
End of study
Randomization
Extended treatment period
Safety follow-up period
No treatment
Screen
Minimum treatment period
Primary Endpoint
• Progression-Free Survival
Key Secondary/Exploratory Endpoints
• Annualized rate of change in FVC (L)
• Categorical decline in FVC and Dlco
• Acute IPF exacerbations
• HRQL – ATAQ-IPF and SGRQ
• Quantitative HRCT scoring
• Functional activity – (6MWT and biosensor)
• Potential predictive biomarker (serum periostin)
Key Inclusion criteria Targeted patient: Definite IPF
• Definite IPF diagnosed by 2011 ATS/ERS/JRS/ALAT criteria – HRCT/SLB eligibility assessments made by centralized review – New onset or established disease (≤ 4 years since diagnosis)
• Age ≥40 years
• FVC ≥40% - ≤90% predicted
• DLCO ≥25% - ≤90% predicted
• FEV1/FVC > 0.7
• Ability to walk ≥100 m unassisted (6MWT)
• No background therapy for IPF
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Study Enrollment
• Target enrollment ~ 250 patients
• Countries participating
– United States, Canada, Australia, France, Poland, Italy, United Kingdom, Germany, Mexico, Peru, Spain
• Total number of sites ~ 100
• Estimated patient recruitment 12 months through October 2014
• Estimated study completion June 2016
THANK YOU !