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AXPAXLI (axitinib intravitreal implant)

Neovascular age-related macular degeneration

Also known as OTX-TKI
Manufacturer
Ocular Therapeutix
Last updated
309 sources

Product information and disease descriptionPlace of product in therapyApproaches to treatmentCurrent treatment options and standard of care

Anti-VEGF monoclonal antibodies and antibody fragments

29 evidence topics · 25 sources

AAO Preferred Practice Pattern: anti-VEGF therapy as first-line treatment

“Anti-VEGF therapies have become first-line therapy for treating and stabilizing most cases of neovascular AMD, and a Cochrane systematic review demonstrates the effectiveness of these agents to maintain VA.” (opens the source at this quote in a new tab)

“(I++, Good quality, Strong recommendation)” (opens the source at this quote in a new tab)

“Adverse events for all anti-VEGF agents include rare risks of arterial thromboembolic events, endophthalmitis, and elevated intraocular pressure.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: management options and agent selection

“Anti-VEGF agents are cost-effective for the management of neovascular AMD, and the choice of which agent to use should be individually tailored based on discussion between the patient and physician.” (opens the source at this quote in a new tab)

“Management options for AMD include observation, antioxidant vitamin and mineral supplements, intravitreal injection of anti-VEGF agents, PDT, and laser photocoagulation surgery.” (opens the source at this quote in a new tab)

Cochrane systematic review of anti-VEGF agents versus control and bevacizumab versus ranibizumab

“We included 16 RCTs that had enrolled a total of 6347 participants with neovascular AMD (the number of participants per trial ranged from 23 to 1208) and identified one potentially relevant ongoing trial.” (opens the source at this quote in a new tab)

“Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same RCTs compared the same regimens with respect to gain of 15 or more letters of visual acuity (RR 0.95, 95% CI 0.81 to 1.12; high-certainty evidence) and loss of fewer than 15 letters of visual acuity (RR 1.00, 95% CI 0.98 to 1.02; high-certainty evidence)” (opens the source at this quote in a new tab)

“Researchers reported endophthalmitis in less than 1% of anti-VEGF-treated participants and in no cases among control groups.” (opens the source at this quote in a new tab)

Ranibizumab: FDA-approved dosing in neovascular AMD

“LUCENTIS 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).” (opens the source at this quote in a new tab)

“Although not as effective, patients may be treated with 3 monthly doses followed by less frequent dosing with regular assessment.” (opens the source at this quote in a new tab)

“Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses. Patients should be assessed regularly.” (opens the source at this quote in a new tab)

Ranibizumab: label efficacy in the pivotal trials

“Almost all LUCENTIS-treated patients (approximately 95%) maintained their visual acuity. Among LUCENTIS-treated patients, 31% to 37% experienced a clinically significant improvement in vision, defined as gaining 15 or more letters at 12 months.” (opens the source at this quote in a new tab)

Ranibizumab: warnings and precautions

“Endophthalmitis and retinal detachments may occur following intravitreal injections. Patients should be monitored following the injection (5.1).” (opens the source at this quote in a new tab)

“There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors (5.3).” (opens the source at this quote in a new tab)

Ranibizumab: MARINA sham-controlled trial

“We enrolled 716 patients in the study. At 12 months, 94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost fewer than 15 letters, as compared with 62.2% of patients receiving sham injections (P<0.001 for both comparisons).” (opens the source at this quote in a new tab)

“During 24 months, presumed endophthalmitis was identified in five patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab.” (opens the source at this quote in a new tab)

Ranibizumab: ANCHOR trial versus verteporfin photodynamic therapy

“Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison).” (opens the source at this quote in a new tab)

“Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison).” (opens the source at this quote in a new tab)

Bevacizumab: off-label intravitreal use

“Bevacizumab is a full-length monoclonal antibody that binds all isoforms of VEGF. It is FDA approved for intravenous use in the treatment of metastatic colorectal, metastatic breast, and non-small cell lung cancer.” (opens the source at this quote in a new tab)

“Because preliminary reports appeared favorable, ophthalmologists began using intravitreal bevacizumab off-label to treat MNV.” (opens the source at this quote in a new tab)

“The off-label status of bevacizumab for neovascular AMD should be included in the discussion; information and a consent form are available from the Ophthalmic Mutual Insurance Company.” (opens the source at this quote in a new tab)

Bevacizumab versus ranibizumab: CATT 1-year results

“In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation.” (opens the source at this quote in a new tab)

“Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively.” (opens the source at this quote in a new tab)

“The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66)” (opens the source at this quote in a new tab)

Bevacizumab versus ranibizumab: CATT 2-year results

“Among patients following the same regimen for two years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference: −1.4 letters; 95% confidence interval (CI): [−3.7, 0.8]; p=0.21).” (opens the source at this quote in a new tab)

“The proportion of patients with ≥1 systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio 1.30; CI [1.07, 1.57]; p=0.009).” (opens the source at this quote in a new tab)

Bevacizumab versus ranibizumab: IVAN 2-year results

“610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses.” (opens the source at this quote in a new tab)

“For BCVA, bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference -1·37 letters, 95% CI -3·75 to 1·01; p=0·26).” (opens the source at this quote in a new tab)

“Ranibizumab and bevacizumab have similar efficacy.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: comparative efficacy and safety of bevacizumab and ranibizumab

“Presently, there does not appear to be a significant difference in efficacy between ranibizumab and bevacizumab.” (opens the source at this quote in a new tab)

“The systemic safety data in the CATT and IVAN studies are inconclusive and two Cochrane systematic reviews have also concluded that if a difference in safety between these anti-VEGF drugs exists, it is minimal.” (opens the source at this quote in a new tab)

Bevacizumab, ranibizumab, and aflibercept: IRIS Registry real-world comparison

“Of 13 859 patients, 6723 received bevacizumab, 2749 received ranibizumab, and 4387 received aflibercept only for 1 year.” (opens the source at this quote in a new tab)

“There was no statistical difference in the age-adjusted or multivariate-adjusted mean logMAR VA change (standard deviation) at 1 year among treatment groups (-0.048 [0.44] bevacizumab, -0.053 [0.46] ranibizumab, -0.040 [0.39] aflibercept; P = 0.46).” (opens the source at this quote in a new tab)

Bevacizumab: EURETINA guideline recommendation on regimen

“Bevacizumab, as needed, failed to meet NI equivalence to monthly ranibizumab, that is, bevacizumab used in a PRN regimen did not reach the superior visual outcome achievable with monthly ranibizumab. Therefore, choice of the proper (fixed monthly) regimen is relevant when off-label bevacizumab is used.” (opens the source at this quote in a new tab)

NICE guideline NG82: anti-VEGF agents considered equivalent

“Offer intravitreal anti-vascular endothelial growth factor (VEGF) treatment for late AMD (wet active) for eyes with visual acuity within the range specified in recommendation 1.5.6.” (opens the source at this quote in a new tab)

“Given the guideline committee's view that there is equivalent clinical effectiveness and safety of different anti-VEGF agents (aflibercept, bevacizumab and ranibizumab), comparable regimens will be more cost effective if the agent has lower net acquisition, administration and monitoring costs.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: cost-effectiveness of bevacizumab and ranibizumab

“This study estimated the cost utility of bevacizumab treatment (relative to no treatment) at approximately $2,700 per quality-adjusted life year ([QALY] for monthly dosing) and $3,300 per QALY (for PRN dosing). In contrast, the cost-effectiveness of ranibizumab was estimated as $63,300/QALY for monthly dosing and $18,600 per QALY for PRN dosing.” (opens the source at this quote in a new tab)

“Wholesale prices of anti-VEGF medications range from $50 to $1,950 per dose, depending on the medication.” (opens the source at this quote in a new tab)

Brolucizumab: description and approved dosing

“Brolucizumab 6 mg is a single-chain variable fragment (the smallest functional portion of an antibody) that binds VEGF-A and was approved by the FDA for the treatment of neovascular AMD.” (opens the source at this quote in a new tab)

“The recommended dose for BEOVU is 6 mg (0.05 mL of 120 mg/mL solution) monthly (approximately every 25-31 days) for the first three doses, followed by one dose of 6 mg (0.05 mL) every 8-12 weeks (2.2).” (opens the source at this quote in a new tab)

Brolucizumab: HAWK and HARRIER 48-week results

“Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye.” (opens the source at this quote in a new tab)

“At Week 48, each brolucizumab arm demonstrated noninferiority to aflibercept in BCVA change from baseline (least squares [LS] mean, +6.6 [6 mg] and +6.1 [3 mg] letters with brolucizumab vs. +6.8 letters with aflibercept [HAWK]; +6.9 [brolucizumab 6 mg] vs. +7.6 [aflibercept] letters [HARRIER]; P < 0.001 for each comparison).” (opens the source at this quote in a new tab)

“Greater than 50% of brolucizumab 6 mg-treated eyes were maintained on q12w dosing through Week 48 (56% [HAWK] and 51% [HARRIER]).” (opens the source at this quote in a new tab)

Brolucizumab: HAWK and HARRIER 96-week results

“At 92w (last DAA), a 45.4% and 38.6% probability was observed for brolucizumab 6 mg patients of maintaining an q12w treatment regimen in HAWK and HARRIER, respectively.” (opens the source at this quote in a new tab)

“The proportion of patients who were maintained on every 12-week dosing through Week 96 was 45% and 39% in HAWK and HARRIER, respectively.” (opens the source at this quote in a new tab)

Brolucizumab: retinal vasculitis and retinal vascular occlusion warning

“Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of BEOVU. These immune-mediated adverse events may occur following the first intravitreal injection. Discontinue treatment with BEOVU in patients who develop these events.” (opens the source at this quote in a new tab)

Brolucizumab: Safety Review Committee analysis of intraocular inflammation in HAWK and HARRIER

“On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%).” (opens the source at this quote in a new tab)

“Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%.” (opens the source at this quote in a new tab)

Brolucizumab: MERLIN every-4-week dosing terminated for intraocular inflammation

“Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab versus 4.5% (0% and 0%) for aflibercept, respectively.” (opens the source at this quote in a new tab)

“However, incidences of IOI, including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination.” (opens the source at this quote in a new tab)

“Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab versus 6.1% (0% and 0.6%) for aflibercept.” (opens the source at this quote in a new tab)

“therefore, brolucizumab should not be used more frequently than every 8 weeks after the loading regimen.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: brolucizumab safety

“After FDA approval, several cases of occlusive retinal vasculitis occurred after intravitreal brolucizumab injection.” (opens the source at this quote in a new tab)

“Brolucizumab is approved for use every 8 to 12 weeks after the loading period, and more frequent administration should be avoided.” (opens the source at this quote in a new tab)

“Although HAWK and HARRIER found a 2.1% incidence of retinal vasculitis with retinal vascular occlusion, postmarketing surveillance revealed a higher incidence of intraocular inflammation.” (opens the source at this quote in a new tab)

Medicare Advantage step therapy for Part B drugs: CMS policy

“issuing new guidance that recognizes Medicare Advantage (MA) plans may use step therapy for Part B drugs, beginning January 1, 2019, as part of a patient-centered care coordination program.” (opens the source at this quote in a new tab)

Medicare Advantage step therapy: bevacizumab-first payer policy example

“Repackaged Avastin, then Eylea or Eylea HD or Pavblu” (opens the source at this quote in a new tab)

“History of a trial of at least 3 consecutive doses given monthly, resulting in minimal clinical response to repackaged Avastin (bevacizumab); or History of contraindication or adverse event(s) to repackaged Avastin (bevacizumab); or Continuation of prior therapy within the past 365 days.” (opens the source at this quote in a new tab)

Step therapy: bevacizumab-first policies and supply disruption

“Following the 2019 Centers for Medicare and Medicaid Services (CMS) decision permitting Medicare Advantage plans to impose step therapy for Part B drugs, many insurers adopted a bevacizumab (Avastin, Genentech/Roche)-first approach.” (opens the source at this quote in a new tab)

“In addition, with rigid fail-first protocols, patients are often required to receive three monthly bevacizumab injections before a switch can be approved.” (opens the source at this quote in a new tab)

“the problem intensified in 2024 with the discontinuation of bevacizumab production from Optum Specialty Pharmacy, the facility responsible for 45% of bevacizumab repackaging in the United States.” (opens the source at this quote in a new tab)

Step therapy: AAO position

“The Academy opposes the adoption of step therapy in Medicare Advantage, which now covers over half of all Medicare beneficiaries, and commercial payer policies.” (opens the source at this quote in a new tab)

ASRS Preferences and Trends survey: agent switching after suboptimal bevacizumab response

“The survey was given electronically to 2,971 members of the society (2,615 regular members and 356 fellows); 1,057 respondents completed the survey (35-percent response rate).” (opens the source at this quote in a new tab)

“For wet AMD patients who have a suboptimal response to Avastin (bevacizumab, Genentech) treatment, 88.4 percent of the physicians say they’ll switch to Eylea (aflibercept, Regeneron).” (opens the source at this quote in a new tab)