FDA approves ranibizumab biosimilar Lucamzi for wet AMD

The FDA approved Lucamzi (ranibizumab-blrz; Xbrane Biopharma), a biosimilar to Lucentis (ranibizumab; Genentech), for neovascular (wet) age-related macular degeneration (AMD) and other serious eye conditions, according to a company announcement. Xbrane said it is finalizing a US launch for 2027 with its partners.¹ The approval followed complete response letters tied to inspection and manufacturing issues, and the application was resubmitted in April 2026, according to trade reports.^2,3

XPLORE phase 3 trial design and end points

Approval rests on XPLORE (NCT03805100), a randomized, double-masked, parallel-group, multicenter phase 3 study of 582 patients with wet AMD conducted at sites in 15 countries between April 2019 and November 2021.^1,4,5 Patients were randomized 1:1 to the investigational ranibizumab biosimilar, registered under the development name Xlucane and published as XSB-001, or to Lucentis, with intravitreal dosing every 4 weeks for 52 weeks.^4,5 Eligible patients were aged 50 years or older with a best corrected visual acuity (BCVA) of 49 to 73 ETDRS letters (20/40 to 20/100 Snellen equivalent).⁴ Mean age at enrollment was 74.1 years, and mean baseline BCVA was 61.7 letters in the biosimilar group and 61.5 letters in the Lucentis group.⁵

Infographic summarizing the XPLORE phase 3 trial of Lucamzi vs Lucentis in wet AMD. 582 patients in 15 countries were randomized 1:1 to monthly 0.5 mg injections for 52 weeks. Mean BCVA gain at week 8 was 4.6 letters with Lucamzi and 6.4 letters with Lucentis, and at week 52 was 6.4 and 7.8 letters. The week 8 difference of –1.8 letters (90% CI, –2.9 to –0.7; 95% CI, –3.1 to –0.5) fell within the ±3.5-letter equivalence margin. No clinically meaningful differences were seen in anatomic secondary end points.

The registered primary end point was change in BCVA from baseline at week 8.⁴ At week 8, the least-squares (LS) mean gain was 4.6 ETDRS letters with the biosimilar and 6.4 letters with Lucentis, for an LS mean difference of –1.8 letters (90% CI, –2.9 to –0.7; 95% CI, –3.1 to –0.5).⁵ Both intervals fell within the prespecified equivalence margin of ±3.5 letters. The 90% CI was the US criterion and the 95% CI applied elsewhere.⁵ At week 52, mean gains were 6.4 and 7.8 letters, respectively (LS mean difference, –1.5 letters; 95% CI, –3.6 to 0.7).⁵

Secondary end points at week 52 included choroidal neovascularization (CNV) size and leakage area on fluorescein angiography, central foveal thickness, subretinal fluid, and retinal pigment epithelium detachment dimensions on OCT.⁴ Additional end points were the proportions of patients losing fewer than 15 letters and gaining 15 or more letters. A subgroup of patients contributed pharmacokinetic samples.⁴ Investigators reported no clinically meaningful differences between groups in central foveal thickness, CNV leakage area, CNV size, or subretinal fluid through week 52.⁵

Safety, labeling, and US launch plans

Through week 52, serious adverse events occurred in 11.3% of patients receiving the biosimilar and 12.1% of those receiving Lucentis.⁴ Investigators reported no clinically meaningful differences between groups in safety or immunogenicity.⁵ Eyes On Eyecare reported the company had not provided prescribing information for Lucamzi.³ The FDA licensed Lucamzi as a biosimilar rather than as an interchangeable product, according to the agency’s Purple Book; the other 4 US ranibizumab biosimilars, Byooviz, Cimerli, Nufymco, and Ranluspec, carry interchangeable designations.⁶

For context, the Lucentis label lists wet AMD, diabetic macular edema, diabetic retinopathy, macular edema after retinal vein occlusion, and myopic CNV, with warnings for endophthalmitis, retinal detachment, and increases in intraocular pressure. Eyes On Eyecare inferred the Lucamzi indications and dosing from the reference product label, so these details are not confirmed for the biosimilar. Wet AMD dosing on the Lucentis label is 0.5 mg monthly, with alternative regimens of 3 monthly doses followed by less frequent injections.³

Serious injection-related adverse reactions occurred in less than 0.1% of intravitreal injections in the Lucentis label, including endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract. These figures describe the reference product and are not Lucamzi data.³

Xbrane is preparing the US launch in partnership with Valorum Biologics, which will handle sales and marketing under a licensing agreement, according to Eyes On Eyecare.³ “FDA approval of Lucamzi is a landmark event for Xbrane, representing a key opportunity to reach many more patients and to realize a return on our development investments,” Martin Åmark, CEO of Xbrane Biopharma, said in a statement.¹ Lucamzi is the same product Xbrane has marketed in Europe as Ximluci since 2023, following European approval in November 2022 based on the XPLORE data.^1,5

References

1. Xbrane Biopharma. FDA approves Lucamzi - biosimilar to Lucentis. News release. October 29, 2026. Accessed November 2, 2026. https://www.xbrane.com/en/fda-approves-lucamzi-biosimilar-to-lucentis/

2. Costa-Ferreira A. After a long wait, Xbrane gets FDA approval for Lucentis biosimilar. Generics Bulletin. October 30, 2026. Accessed November 2, 2026. https://insights.citeline.com/generics-bulletin/products/biosimilars/after-a-long-wait-xbrane-gets-fda-approval-for-lucentis-biosimilar-PNZ6M4JHCBB7RMEIWGSJUBBR5M/

3. Delaney-Gesing A. FDA approves Xbrane Biopharma's Lucentis biosimilar. Eyes On Eyecare. October 30, 2026. Accessed November 2, 2026. https://glance.eyesoneyecare.com/stories/2026-10-30/fda-approves-xbrane-biopharma-s-lucentis-biosimilar/

4. A phase III double-blind, parallel group, multicenter study to compare the efficacy and safety of Xlucane versus Lucentis in patients with neovascular age-related macular degeneration (XPLORE). ClinicalTrials.gov identifier: NCT03805100. Updated November 13, 2023. Accessed November 2, 2026. https://clinicaltrials.gov/study/NCT03805100

5. Loewenstein A, Czumbel N, Ernest J, Dusová J, Pearlman J, Nowosielska A. Randomized trial of biosimilar XSB-001 versus reference ranibizumab in patients with neovascular age-related macular degeneration. Ophthalmol Retina. 2023;7(9):753-761. doi:10.1016/j.oret.2023.05.005

6. US Food and Drug Administration. Purple Book: database of licensed biological products. Ranibizumab. Accessed November 2, 2026. https://purplebooksearch.fda.gov/index.cfm?event=simplesearch&proprietary=Lucamzi&proper=ranibizumab