The primary concerns per Evaluate Vantage are shown below in italics.
The dosing schedule seems to be the biggest concern: monthly dosing is better than quarterly. To which I say, of course! OTLK could have done a non inferiority study monthly-vs-monthly (requiring more patients) or a superiority study monthly-vs-quarterly requiring fewer patients. This is a regulatory strategy that the FDA has already approved in OTLK's other disease indications.
Outlook’s job for now is to get ONS-5010 approved, and the Norse Two data might have smoothed the path ahead. The 228-patient study found that the proportion of patients gaining 15 or more letters in best-corrected visual acuity (BCVA) at 11 months, the primary endpoint, was 41% with ONS-5010 versus 23% with Lucentis. The difference was statistically significant with a p value of 0.0052.
ONS-5010-treated patients also gained a mean of 11.2 letters versus 5.8 letters with Lucentis, a secondary endpoint.
However, when asked, Outlook declined to give details of the baseline visual acuity in each arm, and it will be interesting to see if there are any differences here when full data are reported.
A bigger question hovers around the dosing schedules used in Norse Two. ONS-5010 was administered monthly, while Lucentis was given monthly for the first three months, followed by quarterly dosing. Outlook rightly pointed out that this Lucentis dosing schedule is detailed on the drug’s label. However, the label also states that this regimen is not as effective as once-monthly dosing, the recommended schedule, and in fact leads to an average five-letter loss in visual acuity benefit versus monthly dosing.
Finally, the drug to beat these days is not Lucentis but Regeneron/Bayer’s Eylea. If ONS-5010 does make it to market, Outlook could have more cut-price rivals soon: Eylea is set to lose US patent protection in 2023.
ONS-5010 has already shown non-inferiority to Lucentis in the smaller Norse One trial, and Outlook now plans a filing with the FDA in the first quarter of 2022. Perhaps getting approval will be an easier hurdle to clear than marketing the drug, particularly as Outlook only had $37m in cash at the last count.
The fact that the company needs to raise money explains why Outlook’s stock, after soaring 45% in early trading, ended closing up a more muted 7% yesterday – and is down 10% this morning.
