- Confirmed statistical significance in both objective endpoint (Sign) and subjective endpoint (Symptom)
- Statistical significance achieved for the sign endpoints, CCSS (p=0.0239), a measure of improvement in central corneal damage, and TCSS (p=0.0452), a measure of improvement across all corneal regions.
- Statistical significance achieved for the symptom endpoint, EDS (Eye Dryness Score, p=0.0334)
HanAll Biopharma and Daewoong Pharmaceutical announced topline results from the first US Phase 3 study of HL036 for treatment of dry eye (VELOS-2 study) at a press conference on January 21st.
The VELOS-2 study was conducted in dry eye patients across 12 clinical sites in the United States in collaboration with Ora Inc., a US-based ophthalmic CRO (Contract Research Organization). 637 patients were divided into 2 groups to receive HL036 ophthalmic solution 0.25% or Placebo twice daily for 8 weeks.
For efficacy evaluations, the objective endpoint (Sign) was measured by assessing the improvement of corneal damage at each corneal area including, superior (SCSS), central (CCSS), and inferior (ICSS), and also the total sum of these corneal areas (TCSS). The subjective endpoint (Symptom) was measured by the Ocular Discomfort Score (ODS), a patient-reported assessment of eye discomfort, and Eye Dryness Score (EDS), a patient-reported evaluation of eye dryness. Safety evaluations included all adverse events, not limited to ophthalmic events, that occurred in both groups during the dosing period and analyzed rates between the two groups and association of adverse events to drug exposure.
The VELOS-2 study confirmed statistical significance of HL036 0.25% ophthalmic solution in the endpoints CCSS (p=0.0239), a measure of improvement in central corneal damage, and TCSS (p=0.0452), a measure of improvement across total corneal regions. Achievement of statistical significance in TCSS and CCSS has higher clinical importance than significance observed in ICSS from the HL036 Phase 2 (VELOS-1) study, because TCSS and CCSS reflect ocular surface damage in the most sensitive areas of the cornea and its effect on vision, while ICSS only reflects damage in the lower corneal zone where staining can occur even in normal subjects.
In symptom evaluations, HL036 ophthalmic solution 0.25% demonstrated significant improvement in Ocular Discomfort Score (ODS) from week 2 (p=0.0624) and week 4 (p=0.0570) compared to placebo, but did not achieve statistical significance (p<0.05) at week 8 due to increased placebo effect commonly seen in dry eye studies. However, the study confirmed statistical significance in improving Eye Dryness Score (EDS) at week 8 (p=0.0334), which was used in competitor product Xiidra’s clinical studies as a symptom endpoint.
Most adverse events during the clinical study were mild in severity and there was no difference in rates between the HL036 0.25% ophthalmic solution and placebo groups.
HanAll Biopharma’s CEO, Dr. Seung Kook Park commented, “The VELOS-2 study did not meet the primary endpoint of ICSS, but the achievement of statistical significance in CCSS and TCSS is a compelling milestone in HL036 development as these endpoints are more clinically and commercially meaningful. As a competitor’s product Xiidra was FDA-approved through ICSS (inferior), HL036 has potential to be a more commercially competitive product if HL036 is approved by confirming significance in CCSS or TCSS, which demonstrates efficacy across the total corneal regions.
Based on the results of this study, HanAll Biopharma and Daewoong Pharmaceutical will proceed with a second Phase 3 study as planned, and in parallel, engage in licensing-out to global partners.
The final results of the first Phase 3 (VELOS-2) study will be presented at upcoming international ophthalmologic meetings after completion of biomarker and sub-group analyses.