As Outlook Therapeutics announced top-line results from the first of two registration clinical trials evaluating the safety and efficacy of its formulation of bevacizumab-vikg, ONS-5010, its stock price took a plunge from which it has yet to recover. Yet, the company is looking forward to more data to validate the program.
Lytenava, the brand name for ONS-5010, is for the treatment of wet age-related macular degeneration (AMD). Outlook is seeking US Food and Drug Administration approval under a new Biologics License Application (BLA) of what would be the first injectable ophthalmic formulation of the cancer drug with the brand name Avastin (Genentech/Roche), widely used off-label in retinal disease.
In the 60-patient NORSE 1 trial, ONS-5010 demonstrated anticipated safety, efficacy, and positive proof-of-concept results, according to the company, and there were no statistical differences between the study agent and ranibizumab (Lucentis, Genentech/Roche). The company’s medical adviser, Mark Humayun, MD, PhD, noted that the data observed were “consistent with previously published results for ophthalmic bevacizumab.”
Investors Not Impressed
ONS-5010 may have performed as expected according to the company, but investors may have had different expectations. Outlook’s stock price plunged 37% when the news broke, and it’s only worsened since. Investors may have been looking for bevacizumab-vikg to show statistically significant efficacy superior to ranibizumab.
“NORSE 1 was a clinical experience trial that we undertook according to direction from the FDA, because ONS-5010 had not been tested in the eye,” said Lawrence Kenyon, president, CEO, and CFO of Outlook Therapeutics. “We knew it was not going to show statistical significance.
“The heavy lifting for our BLA will be coming from the NORSE 2 trial, which will include more than 220 patients,” he continued. “NORSE 1 showed signs of efficacy, which we were pleased with, and supports our NORSE 2 clinical trials design.”
Did Investors Miss Message?
Investors likely did not fully understand the purpose of the proof-of-concept NORSE 1 and may have had a reflexive reaction to the results, Kenyon stated. “We have been clear on our messaging: This was not a typical Phase III clinical trial,” he said.
“From our perspective, we have confirmed that ONS-5010 behaves very similar to bevacizumab, which was the thesis all along,” he added. “We are even more encouraged with the possibilities from NORSE 2, and what we expect to see with those results next summer.”
Kenyon noted that NORSE 1 did reveal positive trends for ONS-5010 with 3-line visual acuity gains and no ocular adverse events associated with inflammation, a concern with other anti-VEGF agents.
There were no statistical differences between ranibizumab and ONS-5010 in NORSE 1. Overall, two of 25 patients assigned ONS-5010 achieved better than 15-letter best-corrected visual acuity (BCVA) at month 11 versus five of 23 ranibizumab patients.
In the subgroup analysis of treatment-naïve subjects, six in the ONS-5010 group achieved 15-letters or more BCVA at month 11 versus four of 13 in the ranibizumab arm.
The subgroup analysis of patients who had a baseline visual acuity of <67 letters (20/50 or worse) included two of four patients in the ONS-5010 arm and four of nine in the ranibizumab arm achieving >15 letters at month 11. These key subgroups represent the enrollment criteria for patients in the pivotal NORSE 2 clinical trial.
The second trial excludes patients with vision better than 20/50 at baseline and those who have received prior wet AMD treatment. NORSE 2 is powered for statistical significance, and by excluding such patients, Outlook believes that NORSE 2 has enrolled the optimal patient population for meeting the study endpoint.
The company says it has been in close communication with the FDA, and that it believes that the results from the two trials plus a third safety study – NORSE 3 – will be enough to back a BLA submission in the second half of next year. Kenyon said Outlook will be using the 351(a) PHSA regulatory pathway for the treatment of wet AMD.
Plans are also in the works to aim for regulatory approvals in other parts of the world, including Europe, the UK, and Japan.
Outlook hopes that as the first and only on-label ophthalmic formulation of bevacizumab-vikg approved for treating retinal diseases, ONS-5010 will vie for a share of the more than $9 billion anti-VEGF market. Although it’s early to be talking price, Kenyon said Outlook’s agent will likely be the least expensive FDA-approved anti-VEGF for use in wet AMD and other retinal diseases.