Spotlight Q&A: Outlook Therapeutics — Developing First Ophthalmic Formulation of Bevacizumab for FDA Approval

Larry Kenyon

LaVoieHealthScience Client Spotlight

Following is a Q&A with Lawrence Kenyon, President, CEO and CFO of Outlook Therapeutics (NASDAQ: OTLK), a late-stage clinical biotech company focused on developing the first FDA-approved ophthalmic formulation of bevacizumab-vikg to treat wet age-related macular degeneration (wet AMD) and other retinal diseases.  By way of background for our readers, age-related macular degeneration, AMD, is a common eye condition and a leading cause of vision loss among people age 50 and older. It causes damage to the macula, a small spot near the center of the retina and the part of the eye needed for sharp, central vision.

Wet AMD is a form of advanced AMD in which abnormal blood vessels grow underneath the retina. These vessels can leak fluid and blood, which may lead to swelling and damage of the macula, causing vision loss. With wet AMD, abnormally high levels of vascular endothelial growth factor (VEGF) are secreted in the eyes. Anti-VEGF injection therapy blocks this growth. Outlook Therapeutics is developing an anti-VEGF therapeutic to treat wet AMD and other retinal diseases.

Retinal diseases, including wet AMD, diabetic retinopathy/diabetic macular edema, and retinal vein occlusion, have a prevalence of 34.5 million patients in the United States, United Kingdom, Europe, Japan, China and Australia in 2020. The global market for anti-VEGF drugs in these markets is expected to be in excess of $13 billion in 2020.

NOTE: Outlook Therapeutics will participate in a Virtual Investor KOL Roundtable on Thursday, October 29, 2020 at 10:00 AM ET.  The Company’s executive team and Firas M. Rahhal, MD, of the UCLA Geffen School of Medicine will discuss the current market for retinal disease management and how the Company’s Phase 3 product candidate, if approved, will address current unmet patient needs.  A live video webcast of the KOL roundtable discussion will be available on the Events page of the Investors section of Outlook Therapeutics’ Website ( A Webcast replay will be available two hours following the live presentation and will be accessible for one year.

Thank you for joining us today, Mr. Kenyon. To familiarize our readers with Outlook Therapeutics, could you give us an overview of how the company grew to where it is today, and where you see it heading?

Please call me Larry. Outlook Therapeutics actually grew out of the Company’s previous incarnation as Oncobiologics Inc. In December of 2018, senior leadership made the strategic decision to relaunch as Outlook Therapeutics, and to focus on our lead pipeline drug, ONS-5010 / LYTENAVA™ (bevacizumab-vikg), to pursue the development of this compound as the first ophthalmic formulation of bevacizumab. We intend to seek new BLA approvals in several retinal diseases for LYTENAVA™.

Can you tell me more about how and why this decision was reached?

Although unapproved repackaged IV bevacizumab (Avastin®) is already very widely used off-label to treat wet AMD and other retinal diseases, there is no approved formulation specifically for ophthalmology. We realized that developing an approved ophthalmic formulation of bevacizumab for retinal diseases offered a significant commercial opportunity. Bevacizumab is an anti-VEGF medication, and the global market for treating retinal disease with anti-VEGF therapeutics is currently in excess of $13 billion.

Although there are currently three approved anti-VEGF drugs available for ophthalmic use (LUCENTIS®, EYLEA® and BEOVU®), they are extremely expensive. Due to cost issues, roughly 50% of the wet AMD patients in the United States are treated with unapproved, repackaged IV bevacizumab (Avastin®) that is supplied by compounding pharmacists. These repackaged drugs carry significant risks of contamination, inconsistent potency and problematic availability. We felt that patients would be better served by having the option to use an FDA-approved ophthalmic formulation of bevacizumab that avoided the risks of unapproved repackaged IV bevacizumab, commercialized under a responsible pricing policy that potentially could expand patient access to treatment.

What kinds of problems have emerged with repackaged IV bevacizumab when it is used in treating retinal patients?

With some regularity, the FDA and the professional retinal societies issue warnings about particular compounding pharmacies or batches of repackaged IV bevacizumab from compounders that are contaminated or whose potency is inaccurate, or for syringes that do not function properly or have silicone contamination. The results of impurities, improper drug potency and faulty syringes can have very serious outcomes for patients, including severe ocular inflammation or even blindness.

So is ONS-5010 / LYTENAVA™ a biosimilar then?

No, it is not. Biosimilar drugs can only be approved as substitutions for approved branded drugs in the same indication and dosage. Avastin® is approved for multiple oncology indications, but not for ophthalmology; therefore, it is not possible to create an ophthalmic biosimilar to Avastin®, since Avastin® cannot be a reference product for ophthalmic use. ONS-5010 / LYTENAVA™ will be filed with the U.S. FDA as a new biologic under the 351(a) PHSA regulatory pathway, which is reserved for new drugs and which confers 12 years of market exclusivity upon approval.

What is the status of your clinical program for ONS-5010 / LYTENAVA™?

ONS-5010 / LYTENAVA™ is now in late-stage clinical trials for wet AMD. Our pivotal Phase 3 trial is fully enrolled and powered for statistical significance, and a supplemental safety study is underway to ensure an adequate number of patients are exposed to ONS-5010 to support a BLA filing next year. We expect to report data from the pivotal trial in mid-2021, followed by submission of a new BLA to the FDA during 2021. We anticipate approval for ONS-5010 during 2022.

There is quite a bit of activity in the ophthalmology and retinal disease spaces, with several companies investigating new approaches, including gene therapy, genomic medicine and innovative delivery mechanisms. How do you see ONS-5010 / LYTENAVA™, if it is commercialized, fitting into this future model of the market?

Certainly retinal patients, who often face dire prognoses, will benefit from as wide an array of therapeutic options as possible. That being said, anti-VEGF therapy has been the standard of care for decades, and we anticipate that it will continue to serve millions of patients worldwide for many years to come. Our hope is that ONS-5010 / LYTENAVA™ will be approved so that we can offer retinal physicians and their patients a safe and efficacious, approved, cGMP-produced anti-VEGF drug at a responsible price. We anticipate that, if approved, ONS-5010 / LYTENAVA™ will be a viable treatment option across the whole spectrum of retinal care. In addition to wet AMD, this would include diabetic macular edema (DME) and branch retinal vein occlusion (BRVO).

Besides 12 years of market exclusivity for an ophthalmic bevacizumab, do you anticipate any other marketing advantages for ONS-5010?

Yes, in fact the value of bevacizumab in treating wet AMD and other retinal diseases has recently been validated by step-edit clinical guidance from the Centers for Medicare and Medicaid Services (CMS) mandating that bevacizumab be the first-line treatment option for patients newly diagnosed with wet AMD and other retinal diseases. In other words, according to these CMS guidelines, upon diagnosis retinal patients will first be treated with bevacizumab and may only be moved to other approved branded drugs after “failing” on bevacizumab.

Do you expect to seek approval for ONS-5010 / LYTENAVA™ in other diseases beyond wet AMD?

Yes, we expect to start Phase 3 clinical trials for ONS-5010 in treating diabetic macular edema (DME) and branch retinal vein occlusion (BRVO).

Where do you expect to commercialize ONS-5010 / LYTENAVA™, assuming approval?

Although the first approval we are seeking is with the U.S. FDA, we are also in discussions with the regulatory authorities in Europe and the United Kingdom, and expect also to pursue approvals in Japan and Australia. Additionally, during 2020 we signed a joint venture agreement with Syntone Technologies to manufacture and commercialize ONS-5010 / LYTENAVA™ in the Greater China market.

Is there anything else about Outlook Therapeutics that you would like to share with our readers?

Outlook Therapeutics has assembled a first-class management team with extensive experience in ophthalmology, ophthalmic clinical trials and the regulatory requirements for ophthalmic drug approvals. We are moving forward on all fronts in anticipation of a BLA approval of ONS-5010 / LYTENAVA™ during 2022. Our commercial launch planning is underway, including distribution and outreach to our key stakeholders, and we have cGMP manufacturing partnerships in place to produce and package ONS-5010 / LYTENAVA™ for commercial use; we expect to work with Fujifilm Diosynth Biotechnologies and Ajinomoto Biopharma Services. Additionally, we have a supply agreement in place for a best-in-class pre-filled ophthalmic syringe that will provide greater safety to patients than the syringes currently used in unapproved repackaged IV bevacizumab from compounding pharmacies. We expect to commercialize ONS-5010 / LYTENAVA™, if approved, in both unit-dose vials and pre-filled syringes.

We are excited about the prospects for ONS-5010 / LYTENAVA™. We expect that an approved ophthalmic formulation of this already widely used molecule will bring improved safety and efficacy to patients as well as provide a responsibly priced, approved anti-VEGF option that can benefit the healthcare system across the spectrum of care.


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