What is Outlook Therapeutics working on providing to the retinal disorder treatment space?

Outlook Therapeutics hopes to bring to market an investigational ophthalmic version of bevacizumab, a molecule that has been used to treat retinal disorders for several years but has never received approval from major regulatory agencies to be used as an ophthalmic drug solution. If our ophthalmic bevacizumab is approved, we will potentially enhance the standard of care for patients with disorders like wet AMD, diabetic macular edema, and branch retinal vein occlusion by removing concerns related to off-label repackaged IV product. We firmly believe that if a substance is to be injected into a patient's eye, it should meet the various requirements necessary to earn FDA approval for ophthalmic use. To take this through clinical trials, Outlook Therapeutics had to, among other things, meet certain requirements involving the molecule's stability, pH levels, potency, and osmolarity specifications as well as considerations associated with cGMP requirements and packaging. The importance of meeting such requirements cannot be overstated when it comes to ophthalmic treatments.

How big is the market for this product?

There is a vascular endothelial growth process that creates problems in the back of the eye when it occurs, affecting the patient's central vision. This process leads to wet AMD, the leading cause of vision loss for people aged 50 and up. Approximately fifteen years ago, great discoveries were made in the anti-VEGF category, mitigating the growth of abnormal blood vessels that obstruct vision. Today, off-label repackaged IV bevacizumab accounts for about half the injections that occur per year in the United States, with the other half of the market consisting of FDA-approved but significantly more expensive therapies. The market for this type of medication has grown to approximately US$13 billion globally and US$7 billion within the United States.

In the United States, high-priced anti-VEGF treatment costs nearly US$2,000 per injection. Compounding pharmacies were purchasing IV bevacizumab and separating it into smaller volume vials and syringes and selling it for less than US$100. Doctors were then faced with the unusual choice between paying under US$100 or nearly US$2,000 for drug treatments with potentially very similar performances. As such, Outlook Therapeutics took our target product profile (TPP) to doctors and payers to see whether there was a need for an FDA-approved ophthalmic bevacizumab, considering the off-label version had already captured half the market. An average of 84% of doctors included in the survey indicated they were either interested or very interested, demonstrating a significant market potential for an ophthalmic, FDA-approved bevacizumab. With this in mind, the company received confirmation from the payer research we conducted indicating that they would provide coverage for the drug if it attained FDA approval. We anticipate considerable interest in this drug once it is made commercially available.  

Can you highlight key clinical data that Outlook Therapeutics has obtained for its bevacizumab?

Our Phase 3 NORSE 2 clinical trial was particularly pivotal for our submission with the FDA. It was a randomized masked controlled trial that compared monthly-dosed bevacizumab to ranibizumab dosed consistent with the PIER dosing regimen, involving 228 patients across the United States, over 95% of them being treatment-naive. We were absolutely thrilled with the results. While you hope for a p-value of at least 0.05, indicating a 95% confidence level, for our primary endpoint of percentage of patients gaining 3 lines of vision, we achieved an extra digit with our 0.0052 p-value, demonstrating high statistical significance. Our secondary endpoints also had high statistical significance. For example, we had an average of 11.2 letters gained compared to 5.8 for ranibizumab. Just as importantly, only one out of 340 patients experienced ocular inflammation – aside effect that can occur with this type of treatment. Our NORSE TWO study demonstrated a level of safety and efficacy that we believe could be received positively.

Additionally, we found it important to create a delivery system that will provide doctors enhanced ease of use, since the drug is injected into the patient's eye. Our pre-filled syringe prototypes have tested well so far in advisory boards, and together, our biologic drug solution and delivery system could present a winning combination, if approved.

Where do you hope Outlook Therapeutics will be a year from now?  

Following the submission of our BLA, we hope to receive FDA approval within 12 months of submission. Immediately after, we plan to take the drug to the marketplace. If we can offer the US market an on-label ophthalmic treatment as an anti-VEGF solution, we believe it could be an enhancement to the standard of care in the retina space.