In two phase 3 clinical trials of patients with diabetic macular edema (DME), faricimab (Vabysmo, Genentech) achieved robust vision gains, anatomical improvements, and sustained effect with variable dosing periods ranging up to 16 weeks at the one-year mark.1
The durability of treatment effect, not previously reported in a phase 3 DME trial, demonstrates faricimab’s potential to reduce the treatment burden that accompanies intravitreal anti-VEGF treatment.
NEW OPTION. In January, the FDA approved faricimab for treatment of DME (shown here) and neovascular age-related macular degeneration.
A novel approach. Faricimab is a bispecific monoclonal antibody. It targets two disease pathways, angiopoietin-2 (Ang-2) and VEGF-A, that synergistically drive vascular leakage and inflammation in DME. The FDA approved faricimab for DME earlier this year based on the one-year phase 3 results, which support the hypothesis that inhibiting Ang-2–mediated leakage and inflammation promotes vascular stability beyond anti-VEGF monotherapy.1 (Faricimab also was approved for wet age-related macular degeneration based on results of two other trials.)
The drug’s approval for DME is significant because it offers patients “a new class of medicine that inhibits two disease pathways linked to vision loss and can improve their vision as well as the current standards of care, with potentially fewer injections over time,” said Charles C. Wykoff, MD, PhD, at Retina Consultants of Texas in Houston.
Dr. Wykoff added, “patients with faricimab given at intervals of up to four months achieved noninferior vision gains versus aflibercept given every two months in the first year.” These results held through the second year, with increasing proportions of patients treated via extended dosing, he said.
A tale of two trials. To demonstrate consistency and reproducibility in out-comes, researchers simultaneously conducted two trials at 353 sites worldwide. The studies—YOSEMITE (n = 940) and RHINE (n = 951)—had identical protocols and patient characteristics, with a screening period of up to 28 days, a 96-week treatment period, and a final visit at 100 weeks. Monitoring occurred every four weeks from day 1 to study end.
Patients’ mean age was 61.6 years, and their mean best-corrected visual acuity was 61.9-62.5 ETDRS letters. In YOSEMITE, their mean central subfield thickness was 485-492 μm, versus 466-477 μm in RHINE. Most were treatment-naive, as only 20% to 24% previously received anti-VEGF.
Fixed or adjustable dosing? Patients were randomly assigned to one of three dosing groups:
- faricimab 6 mg every eight weeks, following initial treatment with six monthly loading doses;
- faricimab 6 mg, determined by a personalized treatment interval (PTI) algorithm, following initial treatment with four monthly loading doses; or
- aflibercept 2 mg at fixed eight-week intervals, following five monthly loading doses.
Of note, patients in the PTI cohort were managed via a treat-and-extend approach. After the initial loading doses, they received faricimab every four, eight, 12, or 16 weeks based on treatment response. In addition, all participants attended study visits every four weeks and received sham injections during nonactive dosing visits.
Durability of treatment effect. Primary one-year data from both trials demonstrated that faricimab every eight weeks and faricimab PTI offered noninferior vision gains when compared to aflibercept every eight weeks. In addition, faricimab led to improved anatomical outcomes.
With regard to central subfield thickness (CST), in YOSEMITE, the adjusted mean CST change from baseline was –206.6 μm in those who received faricimab every eight weeks and –196.5 μm in the faricimab PTI group, versus –170.3 μm in those who received aflibercept. In RHINE, these CST outcomes were –195.8 μm for faricimab eight weeks, –187.6 μm for faricimab PTI, and –170.1 μm for aflibercept. Moreover, a higher proportion of faricimab-treated patients achieved absence of retinal fluid, and a large proportion of patients treated with faricimab PTI advanced to dosing every 12 or 16 weeks at one year (71% to 74%). This proportion increased to 78% at the end of year 2.
Faricimab was generally well tolerated, and ocular inflammation events were low across both trials.
1 Wykoff CC et al. The Lancet. 2022;399(10326):741-755.
Relevant financial disclosures—Dr. Wykoff: Genentech: C,S; Regeneron: C,S; Roche: C,S.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Hwang Catholic University of Korea: P; Ministry of Education, Republic of Korea: S.
Dr. Manche Alcon: S; Allergan: S; Avedro: C,S; Carl Zeiss Meditec: S; Johnson & Johnson Vision: C,S; NIH: S; Novartis: S; Placid0: P,S; Presbia: S; Research to Prevent Blindness: S; RxSight: U,S; VacuMed: P,S.
Dr. Ten Hulzen None.
Dr. Wykoff Adverum: C,S; Aerie: S; Aldeyra: S; Alimera Sciences S; Allergan: C; Apellis: C,S; Bausch + Lomb: C; Bayer: C,S; Bionic Vision Technologies: C; Boehringer Ingelheim: S; Chengdu Kanghong: C,S; Clearside Biomedical: C,S; EyePoint: C; Gemini Therapeutics: S; Genentech: C,S; Graybug Vision: S; Gyroscope: C,S; Ionis Pharmaceutical: S; IVERIC Bio: C,S; Kato: C; Kodiak Sciences: C,S; LMRI: S; NGM Biopharmaceuticals: C,S; Novartis: C,S; OccuRx: C; Ocular Therapeutix: C; ONL Therapeutics: C,O; Opthea: C,S; Oxurion: C,S; Palatin: C; PolyPhotonix: C,O; RecensMedical: C,O,S; Regeneron: C,S; RegenXBio: C,S; Roche: C,S; Santen: S; Takeda: C; Visgenx: C,O: Xbrane Biopharma: S.
||Consultant fee, paid advisory boards, or fees for attending a meeting.
||Hired to work for compensation or received a W2 from a company.
|Employee, executive role
||Hired to work in an executive role for compensation or received a W2 from a company.
|Owner of company
||Ownership or controlling interest in a company, other than stock.
||Contracted work, including contracted research.
|Lecture fees/Speakers bureau
||Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
||Beneficiary of patents and/or royalties for intellectual property.
|Equity/Stock/Stock options holder, private corporation
||Equity ownership, stock and/or stock options in privately owned firms, excluding mutual funds.
||Grant support or other financial support from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and\or pharmaceutical companies. Research funding should be disclosed by the principal or named investigator even if your institution receives the grant and manages the funds.
|Stock options, public or private corporation
||Stock options in a public or private company.
|Equity/Stock holder, public corporation
||Equity ownership or stock in publicly traded firms, excluding mutual funds (listed on the stock exchange).
More from this month’s News in Review