Full Press Release Details
Outlook Therapeutics
Provides Regulatory Update on U.S. Food and Drug Administration Review of ONS-5010/LYTENAVA (bevacizumab-vikg) for the Treatment
ISELIN, N.J., December 31, 2025
- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company focused on enhancing
the standard of care for bevacizumab for the treatment of retina diseases, today announced that the U.S. Food and Drug Administration
(FDA) has issued a complete response letter (CRL) to the ONS-5010/LYTENAVA (bevacizumab-vikg) biologics license application (BLA)
resubmission, indicating that the FDA cannot approve the application in its present form for the treatment of wet age-related macular
degeneration (wet AMD).
In the CRL, the FDA noted that
the additional mechanistic and natural history data information provided in the BLA resubmission does not alter the previous review conclusion
that while the one adequate and well-controlled study demonstrated efficacy, the FDA has again recommended that confirmatory evidence
of efficacy be submitted to support the application, however the FDA has not indicated what type of confirmatory evidence would be acceptable.
"Our goal has always been
to provide wet AMD patients and their physicians with a safe, consistent, FDA-approved alternative to compounded Avastin manufactured
in the United States, and that goal has not changed. We are disappointed and disagree with this decision, but we remain fully committed
to taking all necessary steps to receive approval in the United States. We continue to believe strongly in the clinical need and commercial
potential of the first on-label bevacizumab product for patients in the United States that is specifically formulated, manufactured, and
packaged for intravitreal use," commented Bob Jahr, Chief Executive Officer of Outlook Therapeutics.
The ONS-5010 BLA resubmission was
based on the complete data set from the NORSE clinical trial program, which included the successful NORSE TWO adequate and well controlled
pivotal clinical trial as well as confirmatory safety and efficacy data from all other NORSE trials, including NORSE EIGHT, an adequate
and well controlled non-inferiority study evaluating ONS-5010 versus ranibizumab in a 12-week study of treatment na ve patients with
a primary efficacy endpoint at 8 weeks. Outlook Therapeutics continues to believe that the complete data set for NORSE TWO, combined with
the data from the other NORSE clinical trials, provides the required evidence to support approval of the ONS-5010 BLA in the United States.
Outlook Therapeutics is currently
exploring all available pathways for potential approval in the U.S. and intends to continue its efforts to expand into additional
markets in Europe and other regions. As previously announced, LYTENAVA (bevacizumab gamma) was granted Marketing
Authorization by the European Commission in the EU and Marketing Authorization by the Medicines and Healthcare products Regulatory
Agency (MHRA) in the UK for the treatment of wet AMD. In June 2025, LYTENAVA (bevacizumab gamma) became commercially
available in Germany and the UK for the treatment of wet AMD. In addition to current plans to expand its commercial presence in
select countries in Europe, Outlook Therapeutics continues to speak with and explore collaborations with potential commercial and
distribution partners in additional European countries, as well as outside of Europe. LYTENAVA (bevacizumab gamma) is the
first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in adults in the European Union and
Age-related macular degeneration,
AMD, is a common eye condition and a leading cause of vision loss among people aged 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, which lets us see objects that are straight
ahead. Wet AMD, a form of late-stage AMD, is also called neovascular AMD.
In wet AMD, abnormal blood vessels
grow underneath the retina. These vessels leak fluid and blood, which may lead to swelling and damage to the macula, causing vision loss.
Additionally, with wet AMD, abnormally high levels of vascular endothelial growth factor (VEGF) are secreted in the eyes. VEGF is a protein
that promotes the growth of new abnormal blood vessels; anti-VEGF injection therapy blocks this growth and has become the standard-of-care
treatment for wet AMD and other retinal diseases, such as diabetic macular edema and branch retinal vein occlusion.
About ONS-5010 / LYTENAVA
(bevacizumab-vikg, bevacizumab gamma)
ONS-5010/LYTENAVA is an
ophthalmic formulation of bevacizumab produced in the United States for the treatment of wet AMD. LYTENAVA (bevacizumab gamma)
is the subject of a centralized Marketing Authorization granted by the European Commission in the EU and Marketing Authorization granted
by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the treatment of wet AMD.
In the United States, ONS-5010/LYTENAVA
(bevacizumab-vikg) is investigational. In certain European Union Member States ONS-5010/LYTENAVA must receive pricing and
reimbursement approval before it can be sold.
Bevacizumab-vikg (bevacizumab gamma
in the EU and UK) is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human
vascular endothelial growth factor (VEGF) and neutralizes VEGF's biologic activity through a steric blocking of the binding of VEGF
to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding
of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell
proliferation, vascular leakage, and new blood vessel formation in the retina.
About Outlook Therapeutics, Inc.
Outlook Therapeutics is a biopharmaceutical
company focused on the development and commercialization of ONS-5010/LYTENAVA (bevacizumab-vikg, bevacizumab gamma) to enhance
the standard of care for bevacizumab for the treatment of retina diseases. LYTENAVA (bevacizumab gamma) is the first ophthalmic
formulation of bevacizumab to receive European Commission and MHRA Marketing Authorization for the treatment of wet AMD. Outlook Therapeutics
commenced commercial launch of LYTENAVA (bevacizumab gamma) in Germany and the UK as a treatment for wet AMD.
In the United States, ONS-5010/LYTENAVA
(bevacizumab-vikg) is investigational. If approved in the United States, ONS-5010/LYTENAVA , would be the first approved ophthalmic
formulation of bevacizumab for use in retinal indications, including wet AMD.
Forward-Looking Statements
This press release contains
forward-looking statements. All statements other than statements of historical facts are "forward-looking statements,"
including those relating to future events. In some cases, you can identify forward-looking statements by terminology such as
"anticipate," "believe," "continue," "expect," "may," "on
track," "plan," "potential," "target," "will," or "would" the
negative of terms like these or other comparable terminology, and other words or terms of similar meaning. These include, among
others, plans for commercial launch of LYTENAVA in additional markets and the timing thereof, expectations concerning
decisions of regulatory bodies and the timing thereof, including market exclusivity, the future potential to receive approval from
the FDA and the timing thereof, the potential of ONS-5010/LYTENAVA as a treatment for wet AMD, the market opportunity for
LYTENAVA in Europe, the United States and other countries, the ability to successfully launch directly or via partnerships
with other companies, and other statements that are not historical fact. Although Outlook Therapeutics believes that it has a
reasonable basis for the forward-looking statements contained herein, they are based on current expectations about future events
affecting Outlook Therapeutics and are subject to risks, uncertainties, and factors relating to its operations and business
environment, all of which are difficult to predict and many of which are beyond its control. These risk factors include those risks
associated with developing and commercializing pharmaceutical product candidates, including the risk that the data from the NORSE
EIGHT trial does not support the approval by the FDA of the ONS-5010 BLA, the content and timing of decisions by regulatory bodies,
the acceptance of Outlook Therapeutics' products by healthcare professionals and patients as safe, effective, and
cost-effective, the impact of governmental and semi-governmental laws, regulations and guidelines, reliance on third-party service
providers, suppliers, and manufacturers, risks of conducting clinical trials and risks in obtaining necessary regulatory approvals,
the content and timing of decisions by regulatory bodies, the sufficiency of Outlook Therapeutics' resources, as well as those
risks detailed in Outlook Therapeutics' filings with the Securities and Exchange Commission (the SEC), including the Annual
Report on Form 10-K for the fiscal year ended September 30, 2025, filed with the SEC on December 19, 2025, as supplemented by future
reports Outlook Therapeutics files with the SEC, which include uncertainty of market conditions and future impacts related to
macroeconomic factors, including as a result of the ongoing overseas conflicts, tariffs and trade tensions, fluctuations in interest
rates and inflation and potential future bank failures on the global business environment. These risks may cause actual results to
differ materially from those expressed or implied by forward-looking statements in this press release. All forward-looking
statements included in this press release are expressly qualified in their entirety by the foregoing cautionary statements. You are
cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Outlook
Therapeutics does not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of
new information, future events or otherwise, except as may be required under applicable securities law.
Chief Executive Officer JTC Team, LLC