Summary

No 4D-150-specific cost-effectiveness analysis, budget impact model, health technology assessment, announced price, or published analyst price estimate was identified. 4D-150 is in Phase 3 development for wet AMD. The sponsor has not disclosed a price and has said that 4D-150 would likely be priced above a single intravitreal anti-VEGF injection. The sponsor expects 4D-150 to fit the U.S. Medicare Part B buy-and-bill model used by retina clinics, cites flexible pricing enabled by low cost of goods, and describes a value proposition that aligns incentives to long-term disease control. The sponsor estimates the 2025 global branded retinal vascular disease anti-VEGF market at $16 billion, of which approximately $10 billion is wet AMD and approximately $4 billion is DME, and states that more than 600,000 U.S. patients receive regular anti-VEGF therapy across more than 800,000 eyes. Under the Otsuka license, the Asia-Pacific territory represents approximately 10% of the global retinal anti-VEGF market, and 4DMT retains rights to approximately 85% of the commercial potential of 4D-150.

One published U.S. analysis addresses the value of a one-time anti-VEGF gene therapy for nAMD. A discounted cash flow model estimated present values of $208,420.61, $219,093.31, and $17,379.41 for a one-time alternative to lifelong aflibercept, ranibizumab, and bevacizumab, respectively; values ranged from $78,323.19 to $292,449.87 by age at first injection and from $148,422.91 to $388,096.81 by injection frequency. The authors proposed bevacizumab as the base case and recommended reimbursement mechanisms with contingencies for sustained efficacy.

Published U.S. economic evaluations of long-acting anti-VEGF treatments report the following. Over 5 years from a U.S. payer perspective, faricimab dominated aflibercept 2 mg (US$52,797 and 2.80 QALYs versus US$62,367 and 2.72 QALYs; 22.6 versus 34 injections), with a 97% probability of cost-effectiveness at US$100,000/QALY; under a Q8W faricimab regimen the ICER was US$162,175 per QALY. A Regeneron-funded model using 2025 wholesale acquisition costs (aflibercept 8 mg 2677.50 USD and faricimab 2289.65 USD per injection) estimated total 3-year costs for aflibercept 8 mg that were 1978.74 USD lower than faricimab in nAMD (12.25 versus 14.80 injections). For the port delivery system with ranibizumab, one cost-utility analysis found an incremental cost-utility ratio of $75,497/QALY at 1 year, $304,108/QALY at 5 years, and $761,646/QALY at 12 years versus ranibizumab injections; a Medicare cost analysis found that the port delivery system with fixed 6-month refills cost $21,016 over 1 year and $89,218 over 5 years, with break-even at 10.8 ranibizumab, 9.3 aflibercept, and 34.5 bevacizumab injections in year 1. An 11-year cost-utility analysis found aflibercept not cost-effective compared with bevacizumab ($1,151,451/QALY incremental).

Medicare Part B payment limits for July to September 2026 were $743.605 per 1 mg for aflibercept (J0178), $298.683 per 1 mg for aflibercept HD (J0177), $803.255 per 1 mg for aflibercept-ayyh (Q5147), $32.381 per 0.1 mg for faricimab (J2777), $51.090 per 0.1 mg for ranibizumab (J2778), $359.713 per 1 mg for brolucizumab (J0179), and $74.823 per 10 mg for bevacizumab (J9035). At labeled nAMD doses these limits correspond to $1,487.21 per aflibercept 2 mg injection, $1,606.51 per aflibercept-ayyh 2 mg injection, $2,389.46 per aflibercept 8 mg injection, $1,942.86 per faricimab 6 mg injection, $255.45 per ranibizumab 0.5 mg injection, and $2,158.28 per brolucizumab 6 mg injection (calculated). In 2025, Medicare Part B spending was $2,378,138,734 for Vabysmo (J2777; 213,777 beneficiaries), $1,537,858,049 for Eylea (J0178; 222,280 beneficiaries), $1,140,248,051 for Eylea HD (J0177; 99,161 beneficiaries), and $522,266,027 for the aflibercept biosimilar Pavblu (Q5147; 80,140 beneficiaries); the nine branded and biosimilar ophthalmic anti-VEGF codes listed (bevacizumab not included) totaled approximately $5.67 billion (calculated), across all indications. In 2024, Part B spending on Eylea was $2,365,369,089 (293,280 beneficiaries). From 2014 to 2023, Medicare beneficiaries received 36,398,293 intravitreal anti-VEGF injections, and standardized Medicare reimbursement per injection declined for aflibercept from $1527.37 to $1379.54.

For one-time ocular gene therapy, Spark Therapeutics set the wholesale acquisition cost of voretigene neparvovec at $425,000 per eye in January 2018 and introduced an outcomes-based rebate arrangement with short-term efficacy (30 to 90 days) and long-term durability (30 months) measures, a direct-to-payer contracting model, and a proposal to CMS for installment payments.

Economic evaluation or health technology assessment of 4D-150

No evidence found.

Sponsor statements on pricing, reimbursement, and practice economics of 4D-150

“Pricing was not disclosed, but the company said 4D-150 would likely be priced well above a single intravitreal anti-VEGF injection.” (opens the source at this quote in a new tab)
“Management argued that the higher upfront reimbursement could still be attractive because the therapy may reduce long-term treatment burden and help capture patients who otherwise disappear from follow-up care.” (opens the source at this quote in a new tab)
“I think as many as your audience members, I’m sure, are aware that retina clinics today largely fit within a Medicare buy and bill model.” (opens the source at this quote in a new tab)
“I think what we remind folks is that today, the economics of a practice is driven by the price of the medicine, right?” (opens the source at this quote in a new tab)
“We’ve seen data that as early as 18 months, 40% of patients that started on anti-VEGF therapy have fallen off for a variety of reasons.” (opens the source at this quote in a new tab)

Sponsor commercial model: payers, practice economics, and cost of goods

Stakeholder	Quoted statement
Payers	“Unique value proposition aligns incentives to long-term disease control and vision protection”
Payers	“Buy & bill model fit (U.S.)”
Payers	“Flexible pricing enabled by low COGS”
Practice workflow and economics	“Practice economics enhanced”
Practice workflow and economics	“Clinic capacity increased”
Global scalability	“Favorable COGS margin”

“In addition, we expect the relatively low doses required to allow for favorable manufacturing scalability, cost of goods sold, and pricing flexibility compared to conventional IV genetic medicines.” (opens the source at this quote in a new tab)

Sponsor estimates of the anti-VEGF market and addressable population

“Bolus anti-VEGF treatment of retinal vascular diseases represents global branded therapeutic markets of over $16 billion, with wet AMD and DME comprising approximately $14 billion.” (opens the source at this quote in a new tab)

Market segment (2025E)	Quoted estimate
Global branded retinal vascular disease anti-VEGF market	“$16B Global Branded Retinal Vascular Disease Anti-VEGF Market (2025E)”
Wet AMD	“~$10B”
DME	“~$4B”
Other indications	“Other (Inc. RVO, DR) ~$2B”
Otsuka license territory	“APAC territory represents ~10% of global retinal anti-VEGF market”

“In the United States, more than 600,000 patients receive regular anti-VEGF therapy across more than 800,000 eyes.” (opens the source at this quote in a new tab)
“Then by definition, 4DMT, we retain the global commercial rights for the balance, call it 85% or so of what we think is the total commercial potential of 4D-150.” (opens the source at this quote in a new tab)

Sponsor statement on coverage and reimbursement uncertainty for genetic medicines

“Significant uncertainty exists as to the coverage and reimbursement status of any newly approved product, particularly for genetic medicine products” (opens the source at this quote in a new tab)
“For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs.” (opens the source at this quote in a new tab)

Value of a one-time anti-VEGF gene therapy for nAMD: discounted cash flow analysis

“To use discounted cash flow (DCF) analysis to estimate the value creation associated with anti-vascular endothelial growth factor (VEGF) genetic therapy for neovascular age-related macular degeneration (nAMD).” (opens the source at this quote in a new tab)
“Discounted cash flow analysis of intravitreal anti-VEGF treatment for nAMD resulted in a base-case valuation of $208 420.61, $219 093.31, and $17 379.41 for a 1-time alternative treatment to aflibercept, ranibizumab, and bevacizumab, respectively.” (opens the source at this quote in a new tab)
“This figure covaried significantly with anti-VEGF agent according to the patient age at first injection ($78 323.19-$292 449.87) and frequency of injections ($148 422.91-$388 096.81).” (opens the source at this quote in a new tab)
“Instead, bevacizumab should be the base case ($17 379.41), with additional value driven from an improvement in quality of life through clinical superiority.” (opens the source at this quote in a new tab)
“This model can serve as a basis for assessing the price ceiling of myriad gene therapy approaches.” (opens the source at this quote in a new tab)
“Given the high present values for these therapeutics, innovative costing and reimbursement mechanisms should be further explored, with contingencies for sustained efficacy.” (opens the source at this quote in a new tab)

Cost-utility of faricimab versus aflibercept in nAMD from a U.S. payer perspective

“A Markov model of five health states defined by best-corrected visual acuity (BCVA) simulated disease progression over 5 years.” (opens the source at this quote in a new tab)
“The model was conducted from a healthcare payer perspective in the US and developed over a 5-year time horizon in the base-case analysis.” (opens the source at this quote in a new tab)
“Faricimab costs were calculated using HCPCS J2777 (payment limit per 0.1 mg) multiplied by 60 units to represent a 6.0-mg dose.” (opens the source at this quote in a new tab)
“In the base case, faricimab yielded 2.80 QALYs for US$52,797, whereas aflibercept produced 2.72 QALYs at US$62,367.” (opens the source at this quote in a new tab)
“Faricimab required markedly fewer injections over 5 years (22.6 vs 34).” (opens the source at this quote in a new tab)
“Under the Q8W regimen, faricimab was more costly than aflibercept (US$76,008 vs US$62,368) despite higher effectiveness (2.801 vs 2.716 QALYs; incremental QALYs 0.084).” (opens the source at this quote in a new tab)
“The resulting ICER of US$162,175 per QALY exceeded commonly cited WTP thresholds, indicating that faricimab was not cost effective at this dosing interval.” (opens the source at this quote in a new tab)
“Probabilistic analysis showed a 97% probability of faricimab being cost effective at US$100,000/QALY.” (opens the source at this quote in a new tab)

Direct and indirect costs of aflibercept 8 mg versus faricimab in the United States

“Direct costs were estimated based on modeled mean injection numbers and 2025 wholesale acquisition costs per injection (aflibercept 8 mg: 2677.50 USD; faricimab: 2289.65 USD) plus medical monitoring costs.” (opens the source at this quote in a new tab)
“Over a 3-year time horizon, the mean number of injections was lower with aflibercept 8 mg versus faricimab for nAMD (12.25 vs. 14.80 injections) and DME (11.80 vs. 15.65 injections).” (opens the source at this quote in a new tab)
“Total costs (direct and indirect) associated with aflibercept 8 mg were 1978.74 USD lower than faricimab for nAMD and 6032.90 USD lower than faricimab for DME.” (opens the source at this quote in a new tab)

Cost-utility of the port delivery system with ranibizumab

“One-year direct PDS ophthalmic costs totaled $21 825 with 2 ranibizumab fills, whereas ranibizumab injection therapy totaled $18 405 with 11.8 injections.” (opens the source at this quote in a new tab)
“The 1-year incremental PDS $/QALY versus injections was cost effective at $75 497/QALY.” (opens the source at this quote in a new tab)
“Five-year PDS therapy was not incrementally cost effective at $304 108/QALY, nor was the 12-year therapy at $761 646/QALY.” (opens the source at this quote in a new tab)

Medicare cost of the port delivery system versus intravitreal injections

“The mean (SD) number of ranibizumab, aflibercept, and bevacizumab injections to break even with the cost of ranibizumab PDS with 1 refill was 10.8 (1.3), 9.3 (1.1), and 34.5 (4.2), respectively.” (opens the source at this quote in a new tab)
“Ranibizumab PDS with fixed 6-month refills over 1 year cost $21 016 ($2102).” (opens the source at this quote in a new tab)
“In scenario analyses, ranibizumab PDS with refills as needed offered cost savings compared with real-world intravitreal ranibizumab or aflibercept use at 5 years but not at 1 year.” (opens the source at this quote in a new tab)

Cost-utility of bevacizumab, ranibizumab, and aflibercept monotherapy for nAMD

“Aflibercept conferred greater QALY gain for less cost than ranibizumab but was not cost-effective compared to bevacizumab ($1,151,451/QALY incremental CUR).” (opens the source at this quote in a new tab)
“The average ophthalmic cost perspective CUR for bevacizumab was $11,033/QALY, $79,600/QALY for ranibizumab, and $44,801/QALY for aflibercept.” (opens the source at this quote in a new tab)

Medicare Part B spending on ophthalmic anti-VEGF agents, 2025

HCPCS code	Brand name	Total spending, 2025 (Q1-Q4)	Total beneficiaries, 2025 (Q1-Q4)	Total claims, 2025 (Q1-Q4)	Average spending per claim, 2025 (Q1-Q4)
J0178	“EYLEA”	“1537858048.5”	“222280”	“857976”	“1792.4254857”
J0177	“EYLEA HD”	“1140248051.1”	“99161”	“379249”	“3006.5947467”
Q5147	“PAVBLU”	“522266026.53”	“80140”	“259747”	“2010.6720252”
J2777	“VABYSMO”	“2378138734.4”	“213777”	“994661”	“2390.9037697”
J2778	“LUCENTIS”	“44798421.18”	“21507”	“82587”	“542.43913909”
Q5128	“CIMERLI”	“30172535.31”	“19257”	“34255”	“880.821349”
Q5124	“BYOOVIZ”	“4244844.27”	“2334”	“6009”	“706.41442336”
J2779	“SUSVIMO”	“6102918.48”	“493”	“818”	“7460.7805379”
J0179	“BEOVU”	“10213333.7”	“1113”	“4504”	“2267.6140542”

Medicare anti-VEGF injection volume and reimbursement per injection, 2014 to 2023

“From 2014 to 2023, a total of 36 398 293 intravitreal anti-VEGF injections were administered to Medicare beneficiaries.” (opens the source at this quote in a new tab)
“Faricimab demonstrated rapid early uptake after its introduction in 2022 (65 052-556 512 injections).” (opens the source at this quote in a new tab)
“Standardized Medicare reimbursement per injection declined significantly for ranibizumab ($1234.35-$724.74; τ = -1.00; P < 0.001) and aflibercept ($1527.37-$1379.54; τ = -0.82; P = .001), remained stable for brolucizumab, and increased for bevacizumab ($46.76-$300.73; τ = 0.69; P < 0.01).” (opens the source at this quote in a new tab)

Medicare Part B spending attributable to on-label versus off-label anti-VEGF agent mix

“From 2013-2023, 5,178 providers billed Part B for 34.5 million anti-VEGF injections.” (opens the source at this quote in a new tab)
“Equalizing anti-VEGF mix to that of the highest-poverty quartile would have resulted in approximately $4.2 billion lower spending.” (opens the source at this quote in a new tab)

“If an intraocular bevacizumab biosimilar were to be priced at $500, costs to Medicare would increase by $457 million from $3.01 billion to $3.47 billion (15.2% increase).” (opens the source at this quote in a new tab)

Outcomes-based and installment payment models for a one-time ocular gene therapy: voretigene neparvovec

“On January 3, 2018, Spark Therapeutics, Inc., announced that the wholesale acquisition cost for LUXTURNA™ (voretigene neparvovec-rzyl) is $425,000 per dose or per eye.” (opens the source at this quote in a new tab)
“Spark Therapeutics also announced three new payer programs: an outcomes-based rebate arrangement with a long-term durability measure, an innovative contracting model and a proposal to CMS under which payments for LUXTURNA would be made over time.” (opens the source at this quote in a new tab)

“LUXTURNA is distributed in the United States through two distribution models: (1) the traditional buy-and-bill model where the treatment center purchases and pays for the product and then submits a claim to the payer; and (2) our innovative contracting and distribution model, branded Spark PATH (Pioneering Access to Healthcare), that includes options for direct-to-payer contracting and outcomes-based rebates.” (opens the source at this quote in a new tab)
“Further, we will share risk with certain health insurers by paying rebates if patient outcomes fail to meet specified thresholds, thereby linking the payment for LUXTURNA to both short-term efficacy (30-90 days) and longer-term durability (30 months) measures that are unique to this one-time gene therapy.” (opens the source at this quote in a new tab)
“We cannot predict whether the Blueprint may affect our ongoing discussions with CMS to align on our proposal for an installment payment option and flexibility to offer greater outcomes-based rebates.” (opens the source at this quote in a new tab)

Economic burden of retinal diseases for which gene therapy is emerging

“While many retinal diseases were considered, almost half of the articles related to the costs of neovascular age-related macular degeneration (nAMD).” (opens the source at this quote in a new tab)
“Significant cost variations were observed across the studies as costs ranged from 45 USD to almost 30,000 USD per patient per annum, across all conditions combined.” (opens the source at this quote in a new tab)

Model structure, perspective, and time horizon of a cost-effectiveness analysis of a one-time ocular gene therapy

“In this economic analysis, a health state transition model based on visual acuity and field with a lifetime horizon was developed to estimate the cost-effectiveness of voretigene neparvovec-rzyl.” (opens the source at this quote in a new tab)
“Direct costs were derived from the literature. Indirect costs, including educational attainment, productivity, caregiver burden, and governmental programs, were estimated using published literature and data analysis of public national surveys.” (opens the source at this quote in a new tab)
“Costs and benefits were discounted at 3.0% annually.” (opens the source at this quote in a new tab)
“Our results depended on a lifetime model horizon.” (opens the source at this quote in a new tab)

Health state utilities, direct medical costs, and price assumed in the base case

Base case model input	Quoted value
Age at model entry, y, mean (SD) [range]	“15 (10.9) [4-44]”
Health utility, moderate visual impairment	“0.71 (0.04) [0.63-0.78]”
Health utility, severe visual impairment	“0.62 (0.02) [0.58-0.65]”
Health utility, profound visual impairment	“0.52 (0.03) [0.46-0.57]”
Health utility, count fingers	“0.35 (0.03) [0.30-0.40]”
Health utility, hand motion, light perception, or no light perception	“0.15 (0.05) [0.06-0.24]”
Annual direct medical cost, moderate visual impairment, $	“8818 (882) [7055-10 582]”
Annual direct medical cost, hand motion, light perception, or no light perception, $	“13 737 (1374) [10 990-16 485]”
Annual discount rate for costs and utilities, %	“3.0”
Voretigene neparvovec-rzyl, price per injection, $	“854 535”

“Cost of voretigene neparvovec-rzyl based on published wholesale acquisition cost, cost of administration based on Medicare 2018 average national reimbursement for the Comprehensive Ambulatory Payment Classification for a level 2 intraocular procedure and Current Procedural Terminology 67036, vitrectomy, mechanical, pars plana approach.” (opens the source at this quote in a new tab)
“As a sensitivity analysis, we used health utilities from a large study of patients with a variety of ophthalmologic disorders; these health utilities were derived from time tradeoff research based solely on VA and included patients with count fingers, hand motion, light perception, and no light perception.” (opens the source at this quote in a new tab)

Base case costs and quality-adjusted life-years of a one-time ocular gene therapy versus standard care

Cost component and outcome, base case, discounted	Voretigene neparvovec-rzyl	Standard care	Incremental value
Direct medical costs, $	“301 794”	“406 404”	“−104 610”
Drug, $	“854 535”	“0”	“854 535”
Indirect costs, $	“1 063 739”	“2 373 702”	“−1 309 963”
Total costs, $	“2 220 069”	“2 780 106”	“−560 038”
Quality-adjusted life-years	“18.1”	“8.6”	“9.4”

“In the base case, voretigene neparvovec-rzyl compared with standard care was associated with lower total costs ($2.2 million vs $2.8 million) and higher quality-adjusted life-years (18.1 vs 8.6).” (opens the source at this quote in a new tab)
“When indirect costs were excluded, the cost per QALY was $79 618.” (opens the source at this quote in a new tab)

Sensitivity of the incremental cost-effectiveness ratio to durability of the one-time treatment effect

“Voretigene neparvovec-rzyl remains cost-effective if at least 8.8% of the long-term treatment effect continues after year 3 when including indirect costs and 43.3% when excluding indirect costs, assuming a cost threshold of $150 000 per quality-adjusted life-year.” (opens the source at this quote in a new tab)
“Assuming complete loss of the treatment effect immediately after the last trial observation in year 3 resulted in ICERs of $237 140 and $380 185 per QALY with and without consideration of indirect costs, respectively.” (opens the source at this quote in a new tab)
“Consistent with Table 2, the largest individual driver of the model results involves the assumption around the reduction in the long-term treatment effect.” (opens the source at this quote in a new tab)

Timing of cost and benefit under buy-and-bill payment for a one-time therapy

“The costs were driven by the price of the therapy, which, based on the current buy-and-bill practice in the United States, would be incurred in the first year of treatment. However, the benefits, including incremental QALY gains and indirect cost offsets associated with voretigene neparvovec-rzyl, would be distributed over patients’ lifetimes and driven largely by assumptions around the treatment effect duration.” (opens the source at this quote in a new tab)

One-time cost of treating the eligible United States population and the cost per covered enrollee

“an expected 1-time cost of $1.7 billion, or $5.2 million for a private payer with 1 million enrollees” (opens the source at this quote in a new tab)
“Aside from cost-effectiveness, other factors should guide payers’ decisions on covering voretigene neparvovec-rzyl.” (opens the source at this quote in a new tab)

Independent assessment reaching a different incremental cost-effectiveness ratio

“The US Institute for Clinical and Economic Review (ICER-US) presented a base case cost-effectiveness model of voretigene neparvovec-rzyl from the modified societal perspective with an ICER of $480 130 for a patient aged 15 years.” (opens the source at this quote in a new tab)