Outlook Therapeutics, Inc. has received FDA approval for LYTENAVA (bevacizumab-vkg) to treat wet age-related macular degeneration (AMD).
Notably, this news comes just a month after the federal agency acknowledged receipt of the company’s fourth submission attempt for this Biologics License Application (BLA).
First up: Can I get a refresh on its regulatory path?
You bet. Check out the multi-year journey encompassing four BLA submissions, three complete response letters (CRLs), and one appeal (to the FDA) for a fourth (and final) package resubmission.
Regarding the latest BLA submission: The federal agency had set July 29 as its Prescription Drug User Fee Act (PDUFA) target action date.
Now for a rundown on this therapeutic.
Here’s a brief recap of we’ve covered (extensively) since Outlook submitted its first BLA back in 2022:
- The basics: LYTENAVA is an ophthalmic formulation acting as a vascular endothelial growth factor (VEGF) with bevacizumab as its active ingredient.
- About bevacizumab: This is a recombinant humanized monoclonal antibody (mAb) that generally works by identifying and binding to vascular endothelial growth factor (VEGF) to prevent the formation, growth, and spread of potential tumors.
- And in wet AMD: This rundown explains how bevacizumab works in LYTENAVA to neutralize the VEGF’s biologic activity and treat the retinal disease.
And how is it administered?
That would be via an intravitreal (IVT) injection—on a monthly basis (an estimated 28 days)—administered in a single-dose vial only by a qualified physician (ophthalmologist).
- The recommended dosage: 1.25 mg (0.05 mL of 25 mg/mL)
- Take note: The formulation does not contain an anti-microbial preservative
Check out LYTENAVA’s full prescribing information (PI) here.
Before we dive deeper into this PI, let’s talk clinical data.
For the sake of brevity, we’ll refer you to our previous coverage.
One clinical trial worth an honorable mention (and included in its PI): the randomized, multicenter, masked, active-controlled NORSE 2 study (NCT03834753).
Gotcha. Now back to this PI: What should we know?
We’ll start with warnings and precautions. Patient should be monitored—ahead of and up to 60 minutes following the injection—for:
- Endophthalmitis and retinal detachments
- These are generally associated with IVT injections
- Intraocular pressure (IOP) increases
- Arterial thromboembolic events (ATEs)
- Such as nonfatal stroke, myocardial infarction, or vascular death (including deaths of unknown cause)
- Though ATE risk was low in LYTENAVA clinical trials, there is a general potential risk following IVT use of VEGF inhibitors
Any other adverse events to be aware of?
Aside from those mentioned above, the PI also listed adverse events (AEs) based on clinical trial results.
However, because the trials were conducted under widely varying conditions, the AE risks “may not reflect the rates observed in practice,” it emphasized.
As such: The three most common ocular AEs, based on 601 patients exposed to LYTENAVA (compared to ranibizumab 0.5 mg) across five clinical trials:
- Conjunctival hemorrhage (4%)
- Eye pain (2%)
- Vitreous floaters (2%)
How about less common ocular AEs?
Occurring in <1% of LYTENAVA-treated patients in those trials:
- Corneal abrasion
- Dry eye
- Eye irritation
- IOP increase (as previously mentioned)
Duly noted. Tell me what else I should know.
LYTENAVA is now the first and only FDA-approved, on-label ophthalmic formulation of bevacizumab for wet AMD treatment.
- Hear from Outlook CEO Bob Jahr on the significance of this for the U.S. wet AMD community.
And take note: Its U.S. regulatory status is now on par with its status in the European Union (EU) and United Kingdom (UK) where it was previously granted marketing clearance as the first bevacizumab ophthalmic formulation in those regions.
Let’s talk commercial launch plans.
Those are currently in progress, according to Outlook, and will reportedly include offering patient access support services via expanded reimbursement and patient assistance programs.
- The timeframe for this: Before the end of 2027.
And when it is available?
One other significant note: LYTENAVA stands to have an anticipated 12 years of market exclusivity under the Biologics Price Competition and Innovation Act (BPCIA).
What this means: This prevents any generic versions of bevacizumab-vikg from being approved and marketed in the U.S. for that time period.