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 !