September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The novel bispecific monoclonal anti-VEGF/anti-Ang2 antibody RG7716 shows promise in wet age-related macular degeneration patients with suboptimal response to prior anti-VEGF monotherapy
Author Affiliations & Notes
  • Usha Chakravarthy
    Center for Experimental Medicine, Queen's University of Belfast, Belfast, Northern Ireland, United Kingdom
  • Dietmar Schwab
    Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Patrick Cech
    Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Mylene Giraudon
    Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Anne Boulay
    Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Piotr Szczesny
    Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Paul Delmar
    Department of Biometrics, Product Development, F. Hoffmann-La Roche Ltd, Basel , Switzerland
  • Jayashree Sahni
    Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Footnotes
    Commercial Relationships   Usha Chakravarthy, Bayer (F), Hofman La Roche (C), Novartis Pharma (F), Ophthotech (F); Dietmar Schwab, F. Hoffmann-La Roche Ltd (E); Patrick Cech, F.Hoffmann-La Roche Ltd (E); Mylene Giraudon, F.Hoffmann-La Roche Ltd (E); Anne Boulay, F.Hoffmann-La Roche Ltd (E); Piotr Szczesny, F.Hoffmann-La Roche Ltd (E); Paul Delmar, F. Hoffmann-La Roche Ltd (E); Jayashree Sahni, F.Hoffmann-La Roche Ltd (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Usha Chakravarthy, Dietmar Schwab, Patrick Cech, Mylene Giraudon, Anne Boulay, Piotr Szczesny, Paul Delmar, Jayashree Sahni; The novel bispecific monoclonal anti-VEGF/anti-Ang2 antibody RG7716 shows promise in wet age-related macular degeneration patients with suboptimal response to prior anti-VEGF monotherapy. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : A phase 1 study was conducted to investigate RG7716 in patients with wet AMD with prior exposure to multiple anti-VEGF therapies and suboptimal therapeutic response

Methods : Patients with wet AMD with best corrected visual acuity (BCVA) between 20/40 to 20/400 (Snellen equivalent), with persistent CNV activity despite ≥3 intravitreal anti-VEGF treatments in the preceding 6 months, and last IVT ≥4 weeks prior to day 1 were enrolled. The single ascending dose (SAD) enrolled 4 cohorts each with 3 patients (0.5 to 6 mg RG7716). The multiple ascending dose (MAD) enrolled two cohorts each with 6 patients (3 and 6 mg RG7716) who received a total of 3 treatments at 4 weekly intervals.

Results : Both single and multiple administrations of RG7716 were well tolerated in the 24 patients enrolled. Ocular adverse events were reported in 9 study eyes and were generally mild (8), one was classified as moderate severity. Serious systemic adverse events were few (one gastrointestinal hemorrhage was reported 76 days after a single 1.5 mg dose) and one patient was withdrawn for elective cardiothoracic surgery; both were deemed to be unrelated to study drug by the principal investigators. In the SAD and 6 mg RG7716 multiple dose group, BCVA increased from baseline by a median of 7 (range: 0 to 18; n=11) and 7.5 letters (range: 3 to 18, n=6), 28 days after the last dose administration, respectively. Central subfield thickness (CST) decreased from baseline by a median of -42 μm (range: -101 to 10, n=11) and -117 μm (range: -252 to -7, n=6), 28 days after the last dose administration in the SAD and 6 mg MAD group, respectively. Following multiple 3 mg RG7716 doses, no changes were observed in either median BCVA (-0.5, range: -9 to 8; n=6) nor CST (median: -9, range: -188 to -1; n=6).

Conclusions : RG7716 binds VEGF and another key angiogenic factor, angiopoietin-2 (Ang2), as a single molecule. RG7716 was well tolerated and exhibited an overall favorable safety profile. In eyes with wet AMD classified by the investigators as suboptimal responders on multiple anti-VEGF treatments, promising improvements in BCVA and key OCT parameters were observed. Phase 2 studies are underway to evaluate RG7716 in a larger patient population to assess its potential to further enhance anti-VEGF monotherapy efficacy and safety

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

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