Outlook Therapeutics Inc (NASDAQ:OTLK) said it has re-submitted its biologics license application (BLA) to the US Food and Drug Administration (FDA) for ONS-5010, an investigational ophthalmic therapy which, if approved, will be branded as LYTENAVA (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD).
Outlook Therapeutics CEO Russell Trenary said the company has worked diligently over the past three months to provide additional required information not included in its March 2022 submission. This will address requests from the FDA to ensure the BLA is complete for acceptance and review.
"We believe that this re-submission addresses each of the comments and recommendations from the agency, and we are confident in the revised BLA application," Trenary noted in a statement. "We remain committed to bringing ophthalmic bevacizumab to market, which if approved, can provide retina patients with an on-label treatment option that helps patients avoid the health risks associated with unapproved repackaged oncologic IV bevacizumab."
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Terry Dagnon, chief operations officer of Outlook Therapeutics, said: "Our NORSE TWO pivotal trial for ONS-5010 showed compelling efficacy and clinical relevance coupled with a robust safety profile, and we are confident that our investigational drug, if approved, will be a valuable therapeutic option to treat retina diseases.”
Dagnon noted that ONS-5010 is designed and manufactured to be fully compliant with the FDA's criteria for ophthalmic biologics to meet the public health need for an FDA-approved ophthalmic formulation of bevacizumab.
In anticipation of potential FDA marketing approval in 2023, Outlook Therapeutics said it has continued its commercial launch planning. These activities include establishing best-in-class partnerships with FUJIFILM Diosynth Biotechnologies for drug substance, and with drug product manufacturer Ajinomoto Bio-pharma Services for finished drug product. Outlook Therapeutics is also actively building out its distribution and commercial capabilities.
The BLA re-submission is based on the totality of data from Outlook Therapeutics' wet AMD clinical program for ONS-5010, which consists of three completed registration clinical trials, as well as a phase one pharmacokinetic clinical trial and the necessary pre-clinical testing.
NORSE ONE was a clinical experience trial involving 61 wet AMD participants at nine trial sites in Australia. It compared ONS-5010 to ranibizumab (LUCENTIS) as a treatment for wet AMD.
NORSE ONE showed the first markers of efficacy and safety in humans for ONS-5010 ophthalmic bevacizumab. In the trial, ONS-5010 efficacy and safety data were consistent with historical published studies of bevacizumab in ophthalmology. NORSE ONE also supported the trial design and inclusion/exclusion criteria established for NORSE TWO, the pivotal phase three registration clinical trial.
The NORSE TWO phase three pivotal trial enrolled a total of 228 wet AMD patients at 39 clinical trial sites in the United States. It was designed as a superiority study comparing the safety and efficacy of ONS-5010 ophthalmic bevacizumab dosed monthly against ranibizumab (LUCENTIS) dosed according to the PIER dosing regimen described in the LUCENTIS label.
Trial data has clinical relevance
The trial data met both their primary and secondary endpoints with high statistical significance and clinical relevance. For its primary endpoint, 41.7% of patients gained at least 15 letters of vision, and for its secondary endpoints 56.5% of subjects gained 10 letters of vision and 68.5% gained at least five letters.
The key secondary endpoint was met: mean change from baseline to month 11, which was 11.2 letters gained compared to 5.8 letters gained in the ranibizumab arm. The NORSE TWO data also showed that the drug was well-tolerated, consistent with previously reported data for ONS-5010 and prior research.
NORSE THREE was an open-label safety study of ONS-5010 in 197 patients conducted in the United States to provide the necessary number of retina patients dosed with ONS-5010 to complete the requirements for the BLA submission.
Safety results across the first three NORSE trials demonstrated a strong benefit-to-risk safety profile. Across all three ONS-5010 registration trials, there was only one ocular inflammation adverse event, which was reported in NORSE TWO, and the event was treated topically and resolved without sequelae.
The most common adverse reaction (>= 5%) reported in patients receiving ONS-5010 was conjunctival hemorrhage associated with the needle injection procedure (5%). These safety findings continue to support minimal ocular inflammation and safety signals consistent with what was previously reported in the 2011 CATT trial (National Eye Institute) and other large adequate and well-controlled ophthalmic studies of bevacizumab.
As previously announced, if ONS-5010 receives FDA approval, Outlook Therapeutics said it plans to submit a supplementary application (sBLA) for approval to provide the product in a filled syringe that is free from liquid silicone oils and that meets the FDA's specifications for ophthalmic use.
NORSE SEVEN trial compares treatment options
To support the anticipated submission of this sBLA, Outlook Therapeutics is conducting its NORSE SEVEN clinical trial to compare the safety of ONS-5010 in vials versus ONS-5010 in filled syringes.
NORSE SEVEN is expected to enroll approximately 120 subjects with visual impairment due to retinal disorders. Patients will be treated for three months, and patient enrollment in the arm of the study receiving ONS-5010 in vials has already been completed.
Because no currently approved ophthalmic formulations of bevacizumab are available, clinicians wishing to treat retinal patients with bevacizumab have had to use unapproved repackaged IV bevacizumab provided by compounding pharmacies, products that have known risks of contamination and inconsistent potency and availability.
If approved, ONS-5010 can replace the need to use unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.
Contact the author at susie@proactiveinvestors.com