Researcher, PhD Centre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia Modena, Emilia-Romagna, Italy
Abstract: In 2015, the European Medicines Agency (EMA) granted conditional market authorization for Holoclar, a treatment based on ex vivo expanded autologous human corneal epithelial cells aimed at restoring the corneal epithelium in patients with limbal stem cell deficiency (LSCD) from ocular burns. Subsequently, a large-scale pan-European trial was conducted to fulfil EMA requirements to confirm efficacy and safety in patients with moderate to severe LSCD and obtain the full market authorization in the EU. This study presents the design and key findings of HOLOCORE and HOLOCORE FU trials, multinational, multicentre, prospective, open-label, uncontrolled phase 4 clinical trials. HOLOCORE enrolled 80 patients (13 female, 67 male), aged 2 to 84 years, who met the specific inclusion criteria for this treatment. Following the withdrawal of some participants, 69 patients were considered suitable for evaluation. HOLOCORE FU produced the results of 6-year follow-up. The primary parameter assessed was the treatment's efficacy, defined as the proportion of patients with fewer than two quadrants of superficial corneal neo-vascularization, no central corneal involvement by neo-vascularisation, and the absence of epithelial defects at day 360 following Holoclar treatment. Efficacy was estimated at 77% by site investigators (based on real clinical assessments) and 50.9% by independent assessors (based solely on 2D images of the ocular surface). The adverse event analysis revealed that 63.8% were unrelated to Holoclar, while only 7.2% were directly associated with treatment failure with no severe adverse events. LSCD symptoms significantly reduced, from 87% at baseline to 55.7% after 12 months, accompanied by improvements in corneal and conjunctival sensitivity and an overall enhancement in quality of life. Most importantly, Best Corrected Visual Acuity improved from 32.7% to 57.8% following transplantation, with 100% of patients without stromal scarring showing visual improvement after treatment. Based on these results, Holoclar received full market authorization in the EU and the UK in 2024. The treatment demonstrated comparable efficacy and safety to previous trials, solidifying its role in managing moderate to severe LSCD and establishing a model for developing other advanced therapy medical products.
