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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

Limitations of current therapies

22 evidence topics · 23 sources

Summary

Current therapies control exudation but do not cure neovascular AMD, and all FDA-approved options require ongoing intravitreal injections or, for the port delivery system, surgery and refills every 24 weeks. Efficacy observed in registration trials is not reproduced in routine practice. In a US database of 49,485 treatment-naive eyes, participants received a mean of 7.3 injections in year 1 and gained a mean of 0.95 letters, and in SIERRA-AMD (98,821 eyes) mean visual acuity change was -5.2 letters by year 4. In the 1,208-participant CATT trial, 5-year mean change was -3 letters from baseline and -11 letters from year 2, and in SEVEN-UP 34% of study eyes had declined by 15 letters or more at a mean of 7.3 years. Treatment burden contributes to undertreatment: a systematic review of 37 studies reported nonpersistence in up to 50% of patients by 24 months and nonadherence in 32% to 95%; loss to follow-up was 22.2% among 9,007 participants in one US practice cohort; and 48.8% of 130 Norwegian survey respondents received 9 or more injections per year, with 37.7% requiring caregiver support at every appointment. Response is heterogeneous, and there is no consensus definition of non-response. Safety constraints limit some options: brolucizumab carries warnings for retinal vasculitis and retinal vascular occlusion, and the port delivery system carries a boxed warning for an up to 3-fold higher rate of endophthalmitis. Payer step therapy requiring bevacizumab first can delay access to FDA-approved agents.

Real-world visual outcomes and injection frequency: US database of 49,485 eyes

“At 1 year, after a mean of 7.3 anti-VEGF injections, there was a mean gain of 1 letter (0.95 letter; 95% confidence interval [CI] for change in VA, +0.77 to +1.13 letter; P < 0.001).” (opens the source at this quote in a new tab)

“Real-world nAMD patients receive fewer anti-VEGF injections and experience worse visual outcomes compared with patients receiving fixed, frequent therapy in randomized controlled trials.” (opens the source at this quote in a new tab)

Real-world visual outcomes over 4 years: SIERRA-AMD

“A total of 98 821 eyes from 79 885 patients receiving intravitreal anti-VEGF therapy.” (opens the source at this quote in a new tab)

“In eyes with 4-year follow-up, VA changes from baseline (ETDRS letters) were least squares means of +1.1 (95% confidence interval [CI], 1.0;1.3), -1.3 (95%CI, -1.5;-1.0), and -3.1 (95%CI, -3.5;-2.7), and -5.2 (95%CI, -6.0;-4.3) for years 1-4. Mean±SD number of injections was 7.5±1.9, 6.7±2.1, 6.6±2.3, and 6.4±2.3 for years 1-4.” (opens the source at this quote in a new tab)

Undertreatment in real-world practice: literature review

“In real-world practice, patients are usually undertreated, accounting for the VA decline over time. Reasons for undertreatment include the burden of injections and monitoring visits imposed on patients/caregivers.” (opens the source at this quote in a new tab)

Real-world injection number and outcomes: AURA and LUMINOUS

“Patients who received >7 injections (in 1 year) or >14 injections (over 2 years) gained more letters and demonstrated greater vision maintenance (loss of <15 letters) than patients who received fewer injections.” (opens the source at this quote in a new tab)

“At Year 1 (n = 10,168), the mean (SD) VA change was −1.6 (12.6) letters (baseline VA: 58.3 [19.0] letters) with a mean (SD) of 4.7 (3.1) ranibizumab injections.” (opens the source at this quote in a new tab)

Real-world outcomes in the United Kingdom: systematic review

“Twenty-six studies (n=25,761 eyes) were included” (opens the source at this quote in a new tab)

“Longer-term studies reported that the visual gains achieved in the first year of treatment were rarely maintained, with under-treatment a likely contributing factor.” (opens the source at this quote in a new tab)

Long-term visual decline: CATT 5-year follow-up

“VA was obtained for 647 (71%) of 914 living patients with average follow-up time 5.5 years.” (opens the source at this quote in a new tab)

“Mean change in VA was -3 letters from baseline and -11 letters from 2 years.” (opens the source at this quote in a new tab)

“Vision gains during the first 2 years of the trial were not maintained at 5 years.” (opens the source at this quote in a new tab)

Long-term visual decline: SEVEN-UP 7-year follow-up

“Forty-three percent of study eyes had a stable or improved letter score (≥0-letter gain) compared with ANCHOR or MARINA baseline measurements, whereas 34% declined by 15 letters or more, with overall a mean decline of 8.6 letters (P<0.005).” (opens the source at this quote in a new tab)

“Macular atrophy was detected by FAF in 98% of eyes, with a mean area of 9.4 mm(2); the area of atrophy correlated significantly with poor visual outcome (P<0.0001).” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: real-world treatment and loss to follow-up

“Real-world treatment tends to fall short of clinical trial guidelines and protocols, and it results in worse outcomes.” (opens the source at this quote in a new tab)

“Loss to follow-up is not uncommon in patients with neovascular AMD.” (opens the source at this quote in a new tab)

“Risk factors included increased age, male sex, unilateral involvement, diabetes, Medicaid insurance, and race and ethnicity.” (opens the source at this quote in a new tab)

Loss to follow-up: US retina practice cohort

“Among the 9007 patients (mean [SD] age, 81.2 [8.8] years; 5917 [65.7%] female; 7905 [87.8%] white), 2003 (22.2%) were LTFU.” (opens the source at this quote in a new tab)

Loss to follow-up: systematic review and meta-analysis

“We included 52 studies.” (opens the source at this quote in a new tab)

“LTFU rates ranged from <5% to >75% over up to 10 years.” (opens the source at this quote in a new tab)

“Patients who were LTFU had worse visual outcomes even after resuming care.” (opens the source at this quote in a new tab)

Nonadherence and nonpersistence: systematic review

“Nonpersistence occurred early, with up to 50% of patients stopping treatment by 24 months. High rates of nonadherence were similarly reported, occurring in 32% to 95% of patients.” (opens the source at this quote in a new tab)

Nonadherence increases with treatment duration

“NA with gaps of >56 days after the scheduled appointment was detected in 39%, 89%, and 100% of patients in group 1, 2, and 3, respectively (groups 1 and 2 vs group 3, p < 0.001).” (opens the source at this quote in a new tab)

Treatment burden: patient-reported survey

“In total, 130 patients responded to the survey. The majority of patients reported to receive nine or more injections per year (48.8%), and many patients needed caregiver support for every treatment appointment (37.7%).” (opens the source at this quote in a new tab)

“Responders included 910 patients and 890 caregivers” (opens the source at this quote in a new tab)

“Most patients and caregivers reported a number of obstacles in managing wAMD, including the treatment itself (35% and 39%, respectively). Sixteen percent of patients also missed a clinic visit.” (opens the source at this quote in a new tab)

ASRS Preferences and Trends survey: reasons for real-world undertreatment

“The most popular reason given was patient non-compliance with visits, at 35 percent” (opens the source at this quote in a new tab)

Heterogeneous response and lack of a consensus definition of non-response

“Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies.” (opens the source at this quote in a new tab)

NICE guideline NG82: limited benefit of switching agents

“Consider switching anti-VEGF treatment for people with late AMD (wet active) if there are practical reasons for doing so (for example, if a different medicine can be given in a regimen the person prefers), but be aware that clinical benefits are likely to be limited.” (opens the source at this quote in a new tab)

Injection counts associated with vision loss, linear gain, and plateau in United States practice

“At the lower range, those patient eyes that received 4 anti-VEGF injections or fewer in the first year of treatment generally lost vision, approximately 2 to 3 letters at 1 year.” (opens the source at this quote in a new tab)

“In the mid range, a linear relationship was found between mean letters gained and mean number of anti-VEGF injections, up to 10 injections over 1 year, after which the relationship plateaued at approximately 3 to 4 letters gained.” (opens the source at this quote in a new tab)

Older age and worse baseline visual acuity among eyes receiving the fewest injections

“Patient eyes that received 4 anti-VEGF injections or fewer over 1 year generally showed worse mean baseline VA than those patient eyes that received a greater number of injections over 1 year.” (opens the source at this quote in a new tab)

“Those who received 1 anti-VEGF injection had a mean baseline age of 81.1 years, whereas those who received 13 injections over 1 year had a mean baseline age of 78.4 years (Fig 3; Table 3).” (opens the source at this quote in a new tab)

One-year visual acuity change by baseline visual acuity at similar injection frequency

“Specifically, patients with baseline VA of 20/200 or worse, 20/70 to 20/200, 20/40 to 20/70, and 20/40 or better received 6.5, 7.4, 7.5, and 7.3 anti-VEGF injections, respectively, over 1 year.” (opens the source at this quote in a new tab)

“Patients with baseline VA of 20/40 or better tended to lose VA at 1 year, regardless of anti-VEGF injection frequency.” (opens the source at this quote in a new tab)

Adherence, missed visits, and visual acuity in routine anti-VEGF care

“In unadjusted univariable analyses, treatment adherence was related to a higher most recent VA (β = 8.98 letters; CI, 1.34–16.62) and lower odds of VA below driving vision (≤69 letters vs. ≥ 70 letters) (OR = 0.50; CI, 0.25–1.00) among nAMD patients.” (opens the source at this quote in a new tab)

“Number of missed visits was associated with lower most recent VA and lower odds of VA below driving vision in nAMD patients.” (opens the source at this quote in a new tab)

“nAMD patients who received more injections had better self-reported NEIVFQ-25 composite scores in unadjusted analyses.” (opens the source at this quote in a new tab)

Retina specialist views on monitoring and injection frequency as a resource burden

“When asked about the impact of activities for monitoring and injection administration on staff time, the majority of the surveyed retina specialists (62%, 35 of 57) felt that frequency of patient monitoring placed a significant burden on staff time.” (opens the source at this quote in a new tab)

“Forty-nine percent (28 of 57) of retina specialists reported that the frequency of injections was an impactful burden on office space, including waiting rooms and examination rooms.” (opens the source at this quote in a new tab)

“Over one-third of physicians (35%, 20 of 57) considered frequency of patient monitoring to be an important motivator in choosing a treatment to prescribe. Two-thirds of physicians (38 of 57) stated they would find it very desirable to reduce office visits.” (opens the source at this quote in a new tab)