Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Bispecific Anti-VEGF/Angiopoietin-2 antibodies

13 evidence topics · 6 sources

AAO Preferred Practice Pattern: faricimab

“Faricimab-svoa, a humanized bispecific monoclonal antibody for intravitreal use that acts through dual inhibition of both angiopoietin-2 and VEGF-A, was approved by the FDA for the treatment of patients with neovascular AMD.” (opens the source at this quote in a new tab)
“Approximately 80% of eyes could be dosed every 12 weeks or more, and 45% could be dosed every 16 weeks in year 1 and increased to 63% in year 2. Through year 2, the median number of injections in the faricimab group was 10, compared with 15 for aflibercept.” (opens the source at this quote in a new tab)

Faricimab: FDA-approved dosing

“The recommended dose for VABYSMO is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly) for the first 4 doses, followed by optical coherence tomography and visual acuity evaluations 8 and 12 weeks later to inform whether to give a 6 mg dose via intravitreal injection on one of the following three regimens: 1) Weeks 28 and 44; 2) Weeks 24, 36 and 48; or 3) Weeks 20, 28, 36 and 44.” (opens the source at this quote in a new tab)

Faricimab: TENAYA and LUCERNE primary results

“Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept).” (opens the source at this quote in a new tab)
“BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]).” (opens the source at this quote in a new tab)

Faricimab: TENAYA and LUCERNE 2-year results with treat-and-extend dosing

“At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing.” (opens the source at this quote in a new tab)
“Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112.” (opens the source at this quote in a new tab)

Faricimab: label dosing-interval distribution and FDA caveats

“At week 48, after 4 initial monthly doses in the VABYSMO arm, 45% of patients received the Weeks 28 and 44 dosing, 33% of patients received the Weeks 24, 36 and 48 dosing, and the remaining 22% of patients received dosing every 8 weeks.” (opens the source at this quote in a new tab)
“The disease activity criteria, which was instrumental in determining dose frequency, is unvalidated.” (opens the source at this quote in a new tab)
“The clinical efficacy for the second year of the study has not been reviewed.” (opens the source at this quote in a new tab)

Faricimab: safety

“The most common adverse reactions (≥ 5%) reported in patients receiving VABYSMO were cataract (15%) and conjunctival hemorrhage (8%).” (opens the source at this quote in a new tab)

“Recently, case reports of intraocular inflammation (excluding endophthalmitis) with faricimab were as high as 2% and retinal vasculitis with or without occlusion were 0.17 per 10,000 injections (vasculitis) and 0.06 per 10,000 for occlusive vasculitis.” (opens the source at this quote in a new tab)

Faricimab: real-world use in previously treated eyes (TRUCKEE)

“Six-month results included 376 eyes, 337 of which had been previously treated with other anti-VEGF agents with an average of 31.1 prior injections.” (opens the source at this quote in a new tab)

NICE technology appraisal TA800: faricimab

“If patients and their clinicians consider faricimab to be 1 of a range of suitable treatments (including aflibercept and ranibizumab), choose the least expensive treatment.” (opens the source at this quote in a new tab)
“Evidence from clinical trials shows that faricimab is as effective as aflibercept. An indirect comparison of faricimab with ranibizumab also suggests similar clinical effectiveness.” (opens the source at this quote in a new tab)

Network meta-analysis of anti-VEGF agents and regimens

“Forty‐nine RCTs including 23 257 eyes of 23 257 patients were included. No anti‐VEGF drug or treatment regimen provided a better BCVA response compared to the reference.” (opens the source at this quote in a new tab)
“When results are considered simultaneously, faricimab 6.0 mg or aflibercept 8.0 mg in a treatment regimen with an LD followed by either a treat‐and‐extend regimen or a fixed 12‐ or 16‐week regimen appears to provide the optimal balance between visual outcomes, anatomical outcomes and the lowest treatment burden.” (opens the source at this quote in a new tab)

Fixed dosing without rescue treatment in TENAYA and LUCERNE

“From day 1, patients randomly assigned to the faricimab group initially received intravitreal faricimab 6·0 mg every 4 weeks up to week 12 (four injections) and patients in the aflibercept group received intravitreal aflibercept 2·0 mg, per its international label guidance, every 4 weeks up to week 8 (three injections), followed by fixed 8-week dosing to study end, without allowing rescue or additional treatments during the study.” (opens the source at this quote in a new tab)
“Patients in the faricimab group who did not have active disease at weeks 20 and 24 received faricimab at week 28 and continued a 16-week regimen up to week 60.” (opens the source at this quote in a new tab)

Intraocular inflammation and endophthalmitis in TENAYA and LUCERNE at week 48

“Rates of intraocular inflammation were low across both trials.” (opens the source at this quote in a new tab)
“In TENAYA and LUCERNE, at week 48, rates of intraocular inflammation were low and on average reported in 2·0% of patients receiving faricimab and 1·2% of patients receiving aflibercept” (opens the source at this quote in a new tab)
“There was one report of endophthalmitis in the aflibercept group of LUCERNE, which was culture negative.” (opens the source at this quote in a new tab)

Treat-and-extend interval rules and maintenance of extended intervals in year 2

“In brief, dosing intervals could be extended by 4 weeks (up to Q16W) if the patient achieved stable anatomic features, vision, and no new macular hemorrhage.” (opens the source at this quote in a new tab)
“The interval was reduced by 4- or 8-week increments (as low as Q8W) if worsening vision or anatomic features were found, or new macular hemorrhage occurred” (opens the source at this quote in a new tab)
“On average, 71% of patients who achieved the extended dosing interval of Q12W or longer during the fixed-dosing phase in year 1 maintained Q12W or longer dosing without a reduction to Q8W dosing during the T&E PTI dosing phase through year 2” (opens the source at this quote in a new tab)
“Similarly, 69% of patients receiving Q16W dosing during the fixed-dosing phase in year 1 continued to receive that treatment interval without deviation during the T&E PTI dosing phase” (opens the source at this quote in a new tab)

Serious ocular adverse events and intraocular inflammation through week 112

“The proportion of patients with serious ocular AEs in the study eye through week 112 was low and comparable across study arms in TENAYA (faricimab up to Q16W, 14 patients [4.2%]; aflibercept Q8W, 13 patients [3.9%]) and LUCERNE (faricimab up to Q16W, 15 patients [4.5%]; aflibercept Q8W, 16 patients [4.9%]).” (opens the source at this quote in a new tab)
“The incidence of intraocular inflammation (IOI) events through week 112 was low and comparable between patients receiving faricimab up to Q16W (TENAYA, 11 events [3.3%]; LUCERNE, 9 events [2.7%]) and aflibercept Q8W (TENAYA, 5 events [1.5%]; LUCERNE, 10 events [3.1%]; Table 5)” (opens the source at this quote in a new tab)
“All IOI events except 1 were nonserious.” (opens the source at this quote in a new tab)
“Also, no new retinal vasculitis or noninflammatory occlusive events were reported, in line with their absence at the primary analysis.” (opens the source at this quote in a new tab)