Step Therapy to Biosimilars, Branded Anti-VEGF Costs More, Data Show

Patients with neovascular age-related macular degeneration (nAMD) who transitioned from off-label bevacizumab to a biosimilar and then to a branded anti-VEGF agent had longer injection intervals around transitions and higher modeled costs than patients who transitioned directly to either a biosimilar or branded drug, according to a retrospective cohort study of the IRIS (Intelligent Research in Sight) Registry published in the Journal of Vitreoretinal Diseases.¹

Bevacizumab-to-biosimilar-to-branded transitions delayed nAMD care and cost up to 36% more than direct switches, a 182,757-eye registry study found. | Image Credit: Orawan - stock.adobe.com

“The present analysis found concerning differences in nAMD medication transitions,” wrote the researchers. “In addition to demographic differences in medication transitions, biosimilar use was associated with delays in care, and economic modeling suggests that multiple transitions may not be cost-effective.”

Anti-VEGF injections have transformed outcomes for nAMD, but their use carries a substantial economic burden. Medicare Part B claims data have estimated annual expenditures of roughly $10,000 per beneficiary for agents such as ranibizumab and aflibercept, contributing to interest in lower-cost alternatives such as bevacizumab.

Researchers analyzed IRIS Registry data from 2015 through 2024 for patients with nAMD who received intravitreal anti-VEGF injections. Eyes with gaps of 6 months or more between injections were excluded.

Among 182,757 eyes meeting the inclusion criteria, 136,451 received bevacizumab only, 2,184 transitioned from bevacizumab to a biosimilar, 43,787 transitioned from bevacizumab to a branded agent, and 335 transitioned from bevacizumab to a biosimilar and subsequently to a branded agent. Overall, 24.56% of eyes underwent at least 1 medication transition.

The researchers considered the bevacizumab-to-biosimilar-to-branded sequence a potential real-world step-therapy cohort, although the registry did not establish whether individual transitions were specifically required by payers.

Transitions Were Associated With Longer Injection Intervals

Compared with the injection interval immediately preceding transition, the interval increased by 9.849 days after switching from bevacizumab to a biosimilar, 6.192 days after the bevacizumab-to-biosimilar-to-branded sequence, and 0.982 days after switching directly from bevacizumab to a branded agent (all P < .001).

The researchers also found that newer branded agents, including faricimab and aflibercept 8 mg, were associated with an additional 8.6-day delay around transition compared with aflibercept 2 mg (P < .001). However, interval extension after transition did not differ significantly between the newer agents and aflibercept 2 mg.

Patients with Medicaid or Medicare coverage were less likely to undergo medication transition than patients with commercial insurance, with log odds of −0.384 and −0.208, respectively (P < .001). The bevacizumab-only cohort had the lowest proportion of commercially insured patients and the highest proportion of patients with Medicaid.

Multistep Transitions Were the Costliest Pathway

In a Monte Carlo economic simulation using medication costs over a 2-year horizon, the bevacizumab-to-biosimilar-to-branded pathway had an average cost of $26,699 per patient. This was 36.3% higher than the $15,525 cost of a direct bevacizumab-to-biosimilar transition and 11.62% higher than the $21,593 cost of a direct bevacizumab-to-branded transition (both P < .001).

Bevacizumab-only treatment had an average modeled cost of $1,043. The higher cost of the multistep pathway persisted in 5- and 10-year projections.

A sensitivity analysis using Medicare average sale prices also found the multistep pathway to be the most expensive. However, the difference between the multistep pathway and direct bevacizumab-to-branded treatment was only 1.6% and was not statistically significant (P = 1), whereas direct bevacizumab-to-biosimilar treatment was 49.4% less costly than the multistep pathway.

The step-therapy cohort also had the highest injection frequency and the shortest interval extension after transition, findings that may help explain its higher modeled cost. However, the observational study could not establish that payers required a specific number of biosimilar injections or that loading-dose requirements caused the additional costs.

Visual acuity improved across all cohorts, with improvement peaking at approximately 5 months after the first injection before gradually declining. Central subfield thickness decreased across treatment groups. The authors characterized differences in visual acuity as having uncertain clinical significance and concluded that there were minimal clinically significant differences in visual acuity or central subfield thickness among the pathways.

A separate prospective study of 9 US retina practices found that 96.2% of 2225 eligible anti-VEGF prior authorization requests were approved, but 59.6% of the approved requests resulted in a delay in care of more than 24 hours.² The study also found that the median staff time required to obtain a single authorization was 100 minutes.

Together, the findings suggest that medication transitions involving biosimilars and branded anti-VEGF agents may be associated with longer injection intervals and higher modeled costs, particularly when patients undergo multiple sequential transitions.¹ However, the IRIS study was observational, and its economic analysis was a simulation rather than an assessment of actual patient-level costs. The findings therefore do not establish that step therapy itself caused treatment delays, higher costs, or differences in clinical outcomes. The authors called for further research into the clinical and economic consequences of different anti-VEGF treatment pathways before broader step-therapy policies are adopted.

“Given the current use of step therapy mandates and the potential for irreversible vision loss with delays in care, the findings here suggest that multiple transitions can inadvertently promote higher-cost, lower-value approaches than physician-directed care,” wrote the researchers. “The true societal or payer perspective of cost savings will depend on the proportion of patients ultimately requiring multiple transitions, which cannot be determined from this cohort.”

References

1. Berkowitz ST, Gilbert JB, Ross CJ, et al. Intravitreal anti-VEGF injection transitions across bevacizumab, biosimilar, and branded medications: the IRIS Registry study. J VitreoRetin Dis. Published online 2026. doi:10.1177/24741264261455206
2. Dang S, Parke DW, Sodhi GS, et al. Anti-VEGF pharmaceutical prior authorization in retina practices. JAMA Ophthalmol. 2024;142(8):716-721. doi: 10.1001/jamaophthalmol.2024.2217