Five months after the FDA issued its third rejection of Outlook Therapeutics, Inc’s new drug application (NDA) for ONS-5010 (LYTENAVA; bevacizumab-vikg) to treat wet age-related macular degeneration (AMD), the company secured a major win this week:
The federal agency has granted its appeal to resubmit (for a fourth time) its BLA following the completion of a Federal Dispute Resolution (FDR) process.
Let’s start with the basics of this situation.
- Get the rundown on ONS-5010 / LYTENAVA, an intravitreally (IVT)-administered ophthalmic formulation
- For a recap of the candidate’s clinical trial outcomes, see here.
- And for a reminder of Outlook’s three prior BLA submissions (and subsequent FDA rejections) over the last 3 years:
- Click here for details on its first complete response letter (CRL)
- Click here for more on its second CRL
- And click here for the most recent CRL.
The crux of these rejections: Really came down to the need for more clinical data to support LYTENAVA’s submission packages.
Does that same request apply to the third and most recent BLA rejection?
Not quite, as Outlook did include additional data. Rather, the FDA’s latest rejection was on the basis that the revised submission package still didn’t resolve “lack of substantial evidence of effectiveness” stipulated in prior CRLs.
- See here for more on this situation.
Where does that FDR process come into play?
As we reported in late April, Outlook’s response to this was to, essentially, disagree with the federal agency’s BLA rejection via a formal, federally-regulated process. See what this entailed.
How this was done: Outlook submitted a comprehensive presentation consisting of clinical, functional, and pharmacodynamic data as well as safety findings supporting LYTENAVA for wet AMD treatment.
And this clearly worked, right?
Indeed. Per the company, the FDA granted its appeal after concluding “substantial evidence of effectiveness" had been established for the wet AMD candidate.
So what convinced the agency of this evidence?
As Outlook noted, the specific data that did the convincing stemmed from the NORSE TWO trial coupled with confirmatory evidence from “NORSE EIGHT, natural history, and mechanistic and pharmacodynamic data.”
- Check out the findings from the NORSE TWO trial.
- And get a closer look at this positive data from the NORSE EIGHT trial.
And does that mean a fourth BLA submission is expected?
Yup, it does. In fact, Outlook expects to resubmit ONS-5010 / LYTENAVA’s package next month.
To note: This will be a Class 1 resubmission (reserved for submission following CRLs), which means the BLA will feature any one or more of the following pertaining to the candidate:
- Final printed labeling
- Draft labeling
- Safety updates (including original and new data with changes indicated)
- Stability updates
- Plans to perform phase 4 studies
- Assay validation data
See here for more potential items.
What happens once after resubmission?
The waiting period begins (yet again), with the FDA expected to assign a new Prescription Drug User Fee Act (PDUFA) target action date and make a decision within 60 days of the resubmission.
… and the potential?
Pending a successful BLA submission and subsequent FDA review, LYTENAVA could become the first on-label bevacizumab product specifically formulated for IVT retinal use in the United States.
And with this: Outlook previously noted that the formulation would also receive 12 years of regulatory exclusivity—preventing any generic versions of bevacizumab-vikg from being approved and marketed in the U.S. for that time period.