Lytenava

The company's own announcement of the 12-month NORSE TWO results described the trial as enrolling 228 subjects across 39 clinical trial sites in the United States.

The company's own announcement of the 12-month NORSE TWO results described the trial as enrolling 228 subjects across 39 clinical trial sites in the United States.

The company's own 12-month results announcement described the primary endpoint as met in both an intent-to-treat (ITT) primary dataset (23% ranibizumab vs. 41% bevacizumab-vikg, p=0.0052) and a secondary per-protocol (PP) dataset (24% ranibizumab vs. 41% bevacizumab-vikg, p=0.04).

The company's own 12-month results announcement reported that the secondary endpoint of mean BCVA change from baseline to Month 11 was also statistically significant, at p=0.0043 in the intent-to-treat dataset.

The company's own 12-month results announcement reported only one subject with an ocular inflammation adverse event following exposure to bevacizumab-vikg, one related ocular serious adverse event in the bevacizumab-vikg arm (which resolved), and conjunctival hemorrhage as the most common ocular adverse event, and described the safety database as consistent with previously published bevacizumab safety results.

NORSE TWO compared monthly LYTENAVA dosing for one year against a ranibizumab regimen of three monthly loading doses followed by quarterly dosing, rather than against monthly ranibizumab throughout the study.

The LYTENAVA arm had a mean baseline BCVA of 58.8 ETDRS letters.

Before the label's final analysis, the company's preliminary topline announcement reported a mean BCVA increase of “+4.2 letters” for ONS-5010 versus “+6.3 letters” for ranibizumab at Week 8, a difference it described as “-2.257 BCVA letters” (95% CI -4.044, -0.470); these preliminary figures differ slightly from the final Week 8 result in the approved label (Section 3.1.2.8.3 above).

Mean BCVA improved progressively from baseline for the LYTENAVA arm: approximately +3.3 letters at month 1 (week 4), +4.2 letters at month 2 (week 8), and +5.5 letters at month 3 (week 12). Central retinal thickness decreased by approximately 123.9 microns in the LYTENAVA arm and 127.3 microns in the ranibizumab arm at week 12, an anatomic response the companies described as comparable between arms.

NORSE EIGHT did not meet its pre-specified non-inferiority margin of -3.5 letters for the primary endpoint of mean change in BCVA at Week 8, although the LS mean difference at Week 12 (a secondary, non-primary timepoint) was within the non-inferiority margin.

The company's topline results announcement described the ONS-5010 arm as 25 patients and the ranibizumab arm as 23 patients within the 61-patient trial.

The company's topline results announcement reported that 2 of 25 (8%) patients on the ONS-5010 arm and 5 of 23 (22%) patients on the ranibizumab arm gained more than 15 letters of best corrected visual acuity at Month 11, favoring ranibizumab numerically in this small trial.

Among treatment-naive participants, the announcement reported 2 of 6 (33%) patients on the ONS-5010 arm and 4 of 13 (31%) patients on the ranibizumab arm gaining more than 15 letters at Month 11.

The company's topline results announcement reported no statistical differences in safety between ranibizumab and ONS-5010, and zero cases of ocular inflammation.

NORSE ONE was a small, 61-patient clinical experience trial in Australia, roughly 30 subjects per arm, in which a numerically smaller proportion of the ONS-5010 arm than the ranibizumab arm gained 15 or more letters, a result not repeated in the larger pivotal NORSE TWO trial.

The company's safety results announcement described NORSE THREE as an open-label safety study conducted to ensure an adequate number of safety exposures to ONS-5010 were available for the initial BLA submission to the FDA.

The company's safety results announcement described NORSE THREE as enrolling 197 treatment-naive and previously treated subjects with wet AMD, diabetic macular edema (DME), or branch retinal vein occlusion (BRVO), to add safety exposures ahead of the initial BLA submission.

The company's safety results announcement described NORSE THREE as enrolling 197 treatment-naive and previously treated subjects.

The company's safety results announcement reported that 20 of the 197 enrolled patients (10%) experienced an adverse event in the study eye, most commonly associated with the injection procedure rather than the drug itself.

Of the 197 enrolled patients, 20 (10%) experienced an adverse event in the study eye, most commonly associated with the injection procedure. The company described the safety profile as showing no unexpected trends and as consistent with prior published bevacizumab safety data, including the 2011 CATT study.

NORSE THREE had no comparator or masking, so its adverse-event findings cannot be compared statistically with a control arm; it was designed only to add safety exposures to the overall LYTENAVA safety database ahead of the initial BLA submission.

NORSE SEVEN is a single-arm, open-label study comparing ONS-5010 supplied in vials versus a pre-filled syringe, with no ranibizumab or placebo comparator; ClinicalTrials.gov lists the trial as active, not recruiting, with an estimated primary completion date of December 2027, so its results are not yet available.