The company is hoping to commercialize the first FDA-approved ophthalmic formulation of bevacizumab-vikg for retinal disease. It expects to receive BLA approval from the FDA by mid-2022.
Outlook Therapeutics recently presented an update on the clinical progress of bevacizumab-vikg (ONS-5010, Outlook Therapeutics Inc.) for the treatment of wet age-related macular degeneration (wet AMD).
If approved, bevacizumab-vikg would be the first ophthalmic formulation of bevacizumab approved to treat retinal conditions. It is a full-length, humanized anti-vascular endothelial growth factor (VEGF) recombinant monoclonal antibody (mAb) that inhibits VEGF and associated angiogenic activity. It is an investigational ophthalmic formulation of bevacizumab under development to be administered as an intravitreal injection for the treatment of wet AMD and other retinal diseases.
Lawrence A. Kenyon, Outlook Therapeutics’ president, CEO and CFO, said the company was pleased to provide an update on the continued clinical progress that it hopes will culminate with the topline readout of pivotal data in just a few months.
Kenyon was joined on a virtual presentation by Terry Dagnon, COO, and Jeff Evanson, CCO, along with retina specialists Mark Humayun, MD, PhD, medical advisor to Outlook Therapeutics, and Firas Rahhal, MD, senior partner at Retina-Vitreous Associates Medical Group and an associate clinical professor of Ophthalmology at the UCLA School of Medicine.
“Together with Drs. Humayun and Rahhal, both of whom are practicing retina surgeons and well-known authorities in the retinal community, we are confident that ONS-5010, if approved, will offer a valuable new treatment option to clinicians and their retina patients and address many of the shortcomings that currently exist in the treatment landscape for wet AMD,” Kenyon said.
For the past 15 years, major retinal diseases such as wet AMD, diabetic macular edema (DME) and branch retinal vein occlusion (BRVO) have been successfully treated with a class of medications called anti-VEGFs. Such retinal diseases are characterized by excessive growth of abnormal blood vessels under the retina, which if untreated leads to vision loss and even blindness. Anti-VEGF medications control this abnormal growth and have become the standard of care for treating these diseases.
Physicians who wish to treat their retinal patients with a less expensive anti-VEGF drug often use unapproved repackaged IV bevacizumab from compounding pharmacists. Bevacizumab-vikg, if approved, will be the first on-label ophthalmic formulation for the treatment of retinal diseases.
The company’s virtual clinical day opened with an in-depth discussion of Outlook Therapeutics’ overall clinical program for ONS-5010. Of the three clinical trials that will form the data submission to the FDA for a new Biologics License Application (BLA), two of them, NORSE ONE and NORSE THREE, have been completed. Topline results for ONS-5010 from the completed trials demonstrated positive proof-of-concept, anticipated safety and efficacy, and a safety profile consistent with that of prior published data on the use of bevacizumab for ophthalmic conditions.
The remaining registration trial, NORSE TWO, is a Phase 3 trial that will provide pivotal data powered for statistical significance. Outlook Therapeutics expects to provide the topline readout of these data in the third calendar quarter of this year.
Dagnon pointed out that in consultation with the FDA Ophthalmic Division, the company has secured agreement to pursue an innovative clinical program as we move our investigational ophthalmic bevacizumab through its registration trials towards BLA filing.
“Based on the positive signals we have seen in NORSE ONE and NORSE THREE, we expect the data from NORSE TWO to show that ONS-5010 behaves the same as Avastin bevacizumab does, as reported in the seminal CATT study and other prior published research on ophthalmic use of bevacizumab,” he said. “Our goal is to provide the retina community with an approved ophthalmic bevacizumab that avoids the known risks of the unapproved repackaged IV bevacizumab currently supplied by compounding pharmacies.”
According to Humayun and Rahhal, the clinical retina community already is comfortable with the safety and efficacy of the bevacizumab molecule itself in treating retinal disease.
The concern with using an unapproved form arises from the ancillary issues that can arise during the repackaging process outside of a cGMP facility when compounding pharmacies repackage large vials of oncologic IV Avastin into dozens of small non-ophthalmic syringes for use in the eye.
Humayun pointed out that bevacizumab is a validated drug with a known target and mode of action.
“We know how well it behaves,” he explained. “The NORSE TWO trial is not attempting to demonstrate new science. The strength of the ONS-5010 clinical program is that it is structured to provide the retina community with an approved ophthalmic formulation of a drug that we already use, but in a form that offers physicians and our patients all the safety, efficacy and consistency that FDA approval and cGMP manufacturing provide.”
Humayun pointed out that if approved, bevacizumab-vikg would likely be a significant improvement over the unapproved bevacizumab that many doctors are currently using.
However, Rahhal described potential problems with using unapproved repackaged IV bevacizumab, including possible lack of sterility, inconsistent potency or availability, syringe malfunctions, and silicone droplets or other particulates inadvertently injected into patients’ eyes.
“Although the compounding pharmacists who repackage IV bevacizumab do the best they can, there are certainly challenges and likely also some limitations on consistency,” he said. “My biggest concern is that both the process of repackaging and the syringes themselves may often result in patients receiving sub-potent dosing.”
Rahhal said he suspects that underdosing is more common than we realize and could lead to suboptimal clinical outcomes for our patients.
“Having a specific ophthalmic syringe prepared in an appropriately credentialed facility would solve this problem,” he said.
Should NORSE TWO move forward according to plan, Outlook Therapeutics said it expects to receive BLA approval from the FDA by mid-2022, giving it the first approved bevacizumab for use in retinal indications. The company also has the financing to get it through the process, having recently closed a $35 million offering.
According to Evanson, Outlook Therapeutics is working to position bevacizumab-vikg to address both unmet clinical and market needs. If approved, bevacizumab-vikg is not only expected to provide retina patients with the safety and efficacy of an FDA-approved bevacizumab, but the company intends to work collaboratively with payors and the retina community to offer it at a responsible price.
Evanson also discussed the potential value to clinicians and patients of providing bevacizumab-vikg in a pre-filled ophthalmic syringe.
“Assuming we receive FDA approval for bevacizumab-vikg in 2022, we plan at that time to file a supplementary application for approval to provide the product in a pre-filled ophthalmic syringe,” he said. “We would expect syringe approval within four to six months of that application submission.”
Based on market research, Evanson said the company believe the retina community will welcome a pre-filled, silicone-free syringe that meets the strict specifications for ophthalmic use.