You are here

  • Home
  • Archive
  • Volume 105, Issue 5
  • APEX: a phase II randomised clinical trial evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular degeneration

Article Text

Article menu
Download PDFPDF
Clinical science
APEX: a phase II randomised clinical trial evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular degeneration
  1. Michael N. Cohen1,2,
  2. Denis O’Shaughnessy3,
  3. Kate Fisher4,
  4. Jennifer Cerami3,
  5. Carl C Awh5,
  6. Daniel E Salazar3,
  7. Philip Rosenfeld6,
  8. Jeffrey S Heier1
  1. 1 The Retina Service, Ophthalmic Consultants of Boston, Boston, Massachusetts, USA
  2. 2 New England Eye Center, Tufts University School of Medicine, Boston, Massachusetts, USA
  3. 3 Tyrogenex, Inc., Rockville, Maryland, USA
  4. 4 IDDI, Inc., Raleigh, USA
  5. 5 Tennessee Retina, Nashville, Tennessee, USA
  6. 6 Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
  1. Correspondence to Michael N Cohen, Ophthalmic Consultants of Boston, 50, Staniford Street, Suite 600, Boston, MA 02114, USA; mcohen{at}midatlanticretina.com

Abstract

Purpose The safety and efficacy of X-82, an orally administered inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor, was investigated for treatment of wet age-related macular degeneration (AMD) in a phase II clinical trial.

Methods This phase II, randomised, double-masked, placebo-controlled trial enrolled subjects with a prior diagnosis of exudative AMD having received at least two intravitreal injections of anti-VEGF therapy. Subjects were randomised equally into four groups that received either daily 50mg, 100mg or 200mg dosages of X-82 or a placebo tablet. At each 4-week interval visit for 52 weeks, subjects were to be assessed to determine if rescue treatment was needed with anti-VEGF therapy.

Results 157 patients were enrolled. Due to gastrointestinal and hepatobiliary adverse events and the fulfilment of the primary endpoint, the trial was stopped prematurely after a second interim analysis. The primary endpoint of non-inferiority of visual acuity compared with placebo was demonstrated in all groups receiving X-82 (p<0.001). There was a dose-dependent trend in the number of injections over a 52-week period, with the 50 mg (n=40), 100 mg (n=39), 200 mg (n=39) and placebo (n=39) group requiring 6.7, 6.0, 4.7 and 8.1 injections, respectively.

Conclusions X-82 oral therapy in combination with pro re nata anti-VEGF injections showed non-inferiority in visual acuity outcomes while achieving a dose-dependent decrease in the number of anti-VEGF injections compared with placebo. Given the limited tolerability and safety issues observed, X-82 does not have a sufficient benefit to risk profile in treatment of patients with AMD.

  • Vitreous
  • Retina
  • Macula
  • Angiogenesis
  • Choroid
  • randomized controlled trial
  • Macular Degeneration
  • oral
  • exudative macular degeneration

https://doi.org/10.1136/bjophthalmol-2020-316511

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Twitter MichaelNCohenMD.

    • Contributors Data collection: DOS, JC, CCA, DES, PJR, JSH. Article composition: MNC. Statistical analysis: KF, DOS, DES, JC. Draft review and critical revision: MNC, DOS, KF, JC, CCA, DES, PJR, JSH.

    • Funding MNC— Allergan: Consultant/Advisory Board. DO—Tyrogenex Inc.: Employee. KF—None. JC – Tyrogenex Inc.: Consultant. CCA—Allergan: Advisory Board, Honoraium; Apellis Pharma: Investigator, Research Grant; ArcticDX: Consultant, Stockholder; Bausch+Lomb: Consultant, Honoraium; Genentech: Consultant, Investigator, Research Grant, Honoraium; GlaxoSmithKline: Investigator, Research Grant; Hoffman-LaRoche: Investigator, Research Grant; Katalyst Surgical: Consultant, Stockholder, Royalties; Merck Pharma: Investigator, Research Grant; Ophthotec: Investigator, Research Grant; PanOptica: Investigator, Research Grant; Regeneron: Investigator, Research Grant; Volk: Consultant, Honoraria. DES—Tyrogenex Inc: Consultant; Brace Pharma Capital (investor in Tyrogenex Inc.): Consultant PJR—Apellis: Consultant/Advisor, Equity Owner; Boehringer-Ingelheim: Grant Support, Consultant/Advisor; Carl Zeiss Meditec: Grant Support, Consultant/Advisor; Chengdu Kanghong Biotech: Consultant/Advisor; Healios K.K.: Consultant/Advisor; Hemera Biosciences: Consultant/Advisor; Isarna Pharmaceuticals: Consultant/Advisor; Lin Bioscience: Consultant/Advisor; MacRegen: Consultant/Advisor; Ocudyne: Consultant/Advisor, Equity Owner; Ocunexus: Consultant/Advisor; Stealth Biotherapeutics: Grant Support; Tyrogenex Inc.: Grant Support, Consultant/Advisor; Unity Biotechnology: Consultant/Advisor; Verana Health: Equity Owner. JSH—4D Molecular Technologies: Consultant/Advisor; Adverum: Consultant/Advisor, Equity Owner; Aerie: Consultant/Advisor, Grant Support; Aerpio: Consultant/Advisor, Grant Support; Aldeyra: Consultant/Advisor, Equity Owner; Alkahest: Consultant/Advisor; Allegro: Consultant/Advisor, Equity Owner; Allergan: Consultant/Advisor; Annexon: Consultant/Advisor; Apellis: Consultant/Advisor, Grant Support; Array: Consultant/Advisor; Asclepix: Consultant/Advisor; Clearside: Grant Support; Daiichi Sankyo: Grant Support; Eloxx: Consultant/Advisor; Galimedix: Consultant/Advisor; Genentech/Roche: Consultant/Advisor, Grant Support; Generation Bio: Consultant/Advisor; Graybug: Grant Support; Gyroscope: Grant Support; Interface: Consultant/Advisor; iRenix: Consultant/Advisor; Hemera: Grant Support; Janssen R&D: Consultant/Advisor, Grant Support; jCyte: Consultant/Advisor, Equity Owner; Kala: Consultant/Advisor; KalVista: Grant Support; Kanghong: Consultant/Advisor; Kodiak: Consultant/Advisor; NGM Biopharmaceuticals: Consultant/Advisor; Notal Vision: Consultant/Advisor; Novartis: Consultant/Advisor, Grant Support; Ocugenix: Consultant/Advisor; Ocular Therapeutix: Consultant/Advisor, Equity Owner; Board of Directors Member; Omeicos: Consultant/Advisor; Ophthotech: Grant Support; Optos: Grant Support; Optovue: Grant Support; Orbit/Gyroscope: Consultant/Advisor; Regeneron: Consultant/Advisor, Grant Support; Regenxbio: Consultant/Advisor, Grant Support; Retrotope: Consultant/Advisor; Santen: Consultant/Advisor; Scifluor: Consultant/Advisor; Shire: Consultant/Advisor; Stealth Biotherapeutics: Consultant/Advisor, Grant Support; Takeda: Consultant/Advisor; Thrombogenics: Grant Support; Tyrogenex Inc.: Grant Support; Voyant: Consultant/Advisor.

    • Competing interests None declared.

    • Data sharing statement Data are available upon reasonable request.

    • Ethics statement Each study site received institutional review board approval and adhered to the principles outlined in the Declaration of Helsinki. All patients provided his/her written informed consent prior to enrolling.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    Linked Articles

    • At a glance
      Highlights from this issue
      Frank Larkin
      British Journal of Ophthalmology 2021; 105 i-ii Published Online First: 22 Apr 2021. doi: 10.1136/bjophthalmol-2021-319374