Written By: Sheetal Barbade, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Xbrane Biopharma AB a leading Swedish biosimilar developer regarding its Biologics License Application (BLA) for a Ranibizumab biosimilar, developed as a lower-cost alternative to Genentech’s Lucentis. A CRL is a formal communication from the FDA indicating that an application cannot be approved in its current form and requires additional information or corrective actions before possible approval. The CRL was issued to observations following a re-inspection of one of Xbrane’s contract manufacturers.
The FDA’s CRL to Xbrane Biopharma primarily highlights unresolved observations during inspection of one of the company’s contract manufacturing facilities. These findings were observed during the third-quarter 2025 re-inspections of production sites for both the drug substance and drug product. The FDA did not rise any additional scientific, clinical, or biosimilarity concerns, confirming the molecule’s data package and therapeutic equivalence remain intact.
Detailed Analysis of the FDA’s CRL
The unresolved observations concern Good Manufacturing Practice (GMP) compliance at one of Xbrane’s external manufacturing partners. While previous corrective actions were implemented, the FDA concluded that further clarity or documentation was required to confirm adherence to the standards necessary for biologics licensure. This marks a manufacturing-related delay, not a rejection of the drug itself or its biosimilarity data. Such CRLs often seek procedural improvements, facility documentation, or enhanced process control validations rather than clinical or safety data.
Timeline of CRLs Issued to Xbrane for Ranibizumab Biosimilar
Xbrane has faced multiple regulatory hurdles during its FDA BLA process for the ranibizumab biosimilar since 2024. The company first received a CRL from the FDA in early 2024, which led to the withdrawal and subsequent re-submission of the BLA later that year after addressing the agency’s initial manufacturing and documentation concerns. Following re-submissions and inspections, Xbrane received the current CRL in October 2025 citing unresolved manufacturing observations after the third inspection round. Throughout these interactions, the FDA has not questioned the drug’s clinical or biosimilarity data but has focused exclusively on manufacturing compliance issues.
Company Response and Steps Taken by Xbrane
Xbrane Biopharma stated it is collaborating closely with the FDA and its contract manufacturer to fully address the letter’s requirements. The company expects further guidance from the agency and plans to resubmit the BLA once all issues are rectified. The management indicated that internal remediation activities have already begun in coordination with the contract facility. The company intends to discuss these regulatory updates publicly during its Q3 2025 webcast scheduled for October 24.
Leadership Comments
“We are very disappointed about the FDA’s decision to issue a CRL to our BLA. We believe US patients and payors would significantly benefit from a more cost-efficient alternative to existing approved treatments against retinal disorders, and we are committed to work swiftly towards a re-submission of the BLA,” commented Xbrane’s CEO Martin Amark.
About the Drug: Ranibizumab Biosimilar
Xbrane’s ranibizumab biosimilar marketed in Europe as Ximluci / Lucane is a recombinant monoclonal antibody fragment targeting vascular endothelial growth factor-A (VEGF-A). It is used to treat ophthalmic disorders such as age-related macular degeneration (AMD), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV). The drug has already received regulatory approvals from the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and was launched in several European markets in 2023.
Future Direction and Regulatory Path Forward
Following the CRL, Xbrane plans to submit a complete response package to the FDA incorporating additional documentation from the manufacturing site and addressing all inspectional deficiencies. With clinical and analytical data remaining accepted, the company aims to proceed with a standard FDA resubmission and six-month review cycle upon submission. Xbrane continues to position the ranibizumab biosimilar as a cost-effective alternative for retinal disease treatment in the United States, reinforcing its global biosimilar portfolio strategy.
References
Xbrane provides regulatory update on FDA review of its ranibizumab biosimilar candidate, https://xbrane.com/en/mfn_news/xbrane-provides-regulatory-update-on-fda-review-of-its-ranibizumab-biosimilar-candidate-2/
Xbrane to Resubmit BLA for Ranibizumab Biosimilar following FDA CRL, 21 April 2024, Pearce IP, https://www.pearceip.law/2024/04/21/xbrane-to-resubmit-bla-for-ranibizumab-biosimilar-following-fda-crl/
Xbrane Resubmits Ranibizumab Biosimilar BLA to FDA Following Complete Response Letter, https://trial.medpath.com/news/4e9a226804644526/xbrane-resubmits-ranibizumab-biosimilar-bla-to-fda-following-complete-response-letter