What happens after a second FDA Complete Response Letter?

Verrica Pharmaceuticals Form 8-K, filed November 29, 2021

Verrica received a Complete Response Letter (CRL) from the FDA on September 17, 2021 due to open general inspection items at a contract manufacturer (CMO) that were not specific to VP-102. The Company received a General Advice Letter (GAL) from the FDA on September 22, 2021 with recommendations to improve VP-102’s user interface. On November 5, 2021 Verrica was notified that the inspection of the CMO was classified as “voluntary action indicated” (“VAI”), is now closed and that the VAI classification will not directly negatively impact FDA’s assessment of the Company’s NDA. Verrica resubmitted the NDA for VP-102 on November 24, 2021; the resubmission is limited to address the successful resolution of inspection deficiencies identified at the CMO in the CRL, as well as the recommendations included in the General Advice Letter.

FDA Complete Response Letter, August 4, 2022 · page 2

During a recent inspection of the and Rovi Pharma Industrial Services S.A (FEI 3016688535) manufacturing facilities for this application, our field investigators conveyed deficiencies to the representatives of the facilities. Satisfactory resolution of these deficiencies is required before this application may be approved.

CorMedix Form 8-K, filed August 9, 2022

A second Complete Response Letter (CRL) was received from the FDA stating that the DefenCath NDA cannot be approved until deficiencies recently conveyed to the contract manufacturing organization (CMO) and the supplier of the active pharmaceutical ingredient (API) heparin during inspections are resolved to the satisfaction of FDA. There were no other deficiencies related to DefenCath cited in the CRL, and the Company expects that resolution of the site-specific compliance deficiencies will clear a pathway for FDA to approve the DefenCath NDA.

Verrica Pharmaceuticals Form 8-K, filed August 11, 2022

According to the CRL, the only deficiency listed was related to the deficiencies identified at a general reinspection of the contract manufacturing organization (CMO) that manufactures Verrica’s bulk solution drug product. None of the issues identified by FDA during the reinspection were specific to the manufacturing of VP-102.

Verrica Pharmaceuticals Form 8-K, filed August 11, 2022

Verrica has begun working with Piramal Pharma Solutions to manufacture bulk solution for VP-102 at their Sellersville, Pennsylvania site. Verrica will continue to work closely with Piramal and the FDA to facilitate a timely technology transfer and production quality at the facility.

CorMedix Form 8-K, filed April 26, 2023

At the Type A meeting, the FDA informed CorMedix that it is in receipt of the close out report for inspectional observations received from its existing contract manufacturing organization (“CMO 1”), and NDA resubmission with CMO 1 can be done at the Company’s discretion. The FDA may conduct a pre-approval inspection at the facility as part of the NDA review process.

CorMedix Form 8-K, filed June 21, 2023

today announced that the resubmission of the New Drug Application (NDA) for DefenCath has been accepted for filing by the U.S. Food and Drug Administration (FDA). The Agency considers the resubmission as a complete, Class 2 response with a six-month review, and has assigned a Prescription Drug User Fee Act (PDUFA) target action date of November 15, 2023.

Aldeyra Therapeutics Form 8-K, filed June 17, 2025

Per FDA agreement, the only new clinical data included in the resubmitted NDA were from the recently completed dry eye chamber trial, which achieved the primary endpoint.

Outlook Therapeutics Form 10-K, filed December 19, 2025

we resubmitted the BLA application for ONS-5010/LYTENAVA on February 27, 2025, and received a subsequent CRL on August 27, 2025. Following a September 2025 Type A meeting with the FDA, we resubmitted the ONS-5010/LYTENAVA BLA on November 3, 2025 and received a PDUFA goal date of December 31, 2025 from the FDA.

Outlook Therapeutics Form 10-K, filed December 19, 2025

On August 27, 2025, we received a second CRL from the FDA. This CRL included only one deficiency, for a lack of substantial evidence of effectiveness. In the CRL, the FDA advised that, because ONS-5010 did not meet the primary efficacy endpoint in NORSE EIGHT, it is recommended that confirmatory evidence of efficacy be submitted to support the application for ONS-5010. Additionally, the FDA reiterated that NORSE TWO met its primary endpoint for effectiveness.

CorMedix Form 10-K, filed March 5, 2026

On November 15, 2023, we announced that the FDA approved the new drug application (“NDA”) for DefenCath, an antimicrobial catheter lock solution (“CLS”) (a formulation of taurolidine 13.5 mg/mL, and heparin 1000 USP Units/mL) indicated to reduce the incidence of catheter-related bloodstream infections (“CRBSI”) in adult patients with kidney failure receiving chronic hemodialysis through a central venous catheter (“CVC”). We launched DefenCath commercially in April 2024 in the inpatient setting and July 2024 in the outpatient hemodialysis setting, and it is the largest contributor to our net sales.

Verrica Pharmaceuticals Form 10-K, filed March 11, 2026

On July 21, 2023, YCANTH (VP-102) (cantharidin) 0.7% topical solution was the first product approved by the FDA for the treatment of molluscum in adult and pediatric patients two years of age and older. We commercially launched YCANTH (VP-102) in August 2023 in the United States for the treatment of molluscum.

Outlook Therapeutics Form 8-K, filed March 16, 2026

Moreover, on December 31, 2025, we reported that we had received a third Complete Response Letter, or CRL, with respect to our Biologics License Application, or BLA, for ONS-5010, and the U.S. Food and Drug Administration, or FDA, has again recommended that confirmatory evidence of efficacy be submitted to support the application. However, the FDA did not indicate in the CRL what type of confirmatory evidence would be acceptable, and it is possible that we may need to conduct additional clinical and/or non-clinical studies of ONS-5010 in order to satisfy the FDA’s requirements

Outlook Therapeutics Form 8-K, filed April 7, 2026

today announced that it submitted a formal dispute resolution request (FDRR) to the U.S. Food and Drug Administration (FDA) as a follow-up to its recent Type A meeting regarding the December 30, 2025 Complete Response Letter (CRL) for the Biologics License Application (BLA) for ONS-5010/LYTENAVA™ (bevacizumab-vikg) for the treatment of neovascular age-related macular degeneration. The FDA has accepted the FDRR and has granted a meeting with the deciding official to be conducted in April 2026.

FDA Complete Response Letter, April 10, 2026 · page 1

This BLA resubmission primary clinical review team, supervisory leadership in the Office of Therapeutic Products, and subject matter experts from Oncology Center of Excellence unanimously determined data presented are insufficient to conclude substantial evidence of effectiveness of vusolimogene oderparepvec for treatment of unresectable advanced cutaneous melanoma.

FDA Complete Response Letter, April 10, 2026 · page 6

To address these deficiencies, you must conduct and provide the results from adequate and well-controlled clinical trial(s) which demonstrate substantial evidence of effectiveness.

Outlook Therapeutics Form 8-K, filed May 26, 2026

today announced that the U.S. Food and Drug Administration (FDA) has granted the appeal following completion of the Formal Dispute Resolution (FDR) process with the Office of New Drugs (OND). The FDA concluded that substantial evidence of effectiveness has been established for LYTENAVA™ for the treatment of neovascular age-related macular degeneration (nAMD). As a result, Outlook Therapeutics expects to resubmit the ONS-5010/LYTENAVA™ (bevacizumab-vikg) Biologics License Application (BLA) in June 2026.

Outlook Therapeutics Form 8-K, filed June 1, 2026

The FDR decision directed the Division of Ophthalmology and Office of Specialty Medicine to work with Outlook Therapeutics to focus on reach ing an agreement on final product labeling. Additionally, as indicated in the formal decision, this will be a Class 1 resubmission with a PDUFA date and decision expected within 60 days of FDA’s receipt of the resubmission.

Outlook Therapeutics Form 8-K, filed June 1, 2026

today announced the resubmission of its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ONS-5010/LYTENAVA™ for the treatment of neovascular age-related macular degeneration (nAMD).

Replimune Form 10-K, filed June 29, 2026

We announced on May 29, 2026, that following collaborative communications with the FDA, the Company and the FDA aligned on a path forward for resubmission and reconsideration of the BLA for RP1 in combination with nivolumab for the treatment of advanced melanoma.

Replimune Form 10-K, filed June 29, 2026

On June 26, 2026 we announced the FDA accepted the BLA resubmission as a Class 1 resubmission with an action date of August 2, 2026. The FDA also stated that they would convene an advisory committee meeting in late July 2026.

Replimune Form 8-K, filed July 31, 2026

The committee then voted 10 to 3, on the question: "Are the efficacy results from IGNYTE evaluable and clinically meaningful?"

Replimune Form 8-K, filed August 7, 2026

today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for TUDRIQEV TM (vusolimogene oderparepvec-wtpg), previously referred to as RP1, in combination with nivolumab for the treatment of adults with unresectable advanced cutaneous melanoma who experienced disease progression on an anti-PD-1 antibody-based regimen.

Aldeyra Therapeutics Form 8-K, filed September 29, 2026

The FDRR, which is expected to be reviewed by the FDA’s Office of New Drugs (OND), is designed to appeal the March 16, 2026 Complete Response Letter that denied approval of a New Drug Application (NDA) for reproxalap for the treatment of dry eye disease. Submission of the FDRR and a meeting with the OND are expected in the fourth quarter of 2026.

Aldeyra Therapeutics Form 8-K, filed September 29, 2026

Following an NDA submission and two NDA resubmissions of reproxalap for the treatment of dry eye disease, Aldeyra has received three Complete Response Letters, the first two of which recommended an additional clinical trial to “demonstrate a positive effect on the treatment of ocular symptoms of dry eye” and the most recent of which did not request further clinical trials but stated that the “totality of evidence from the completed clinical trials does not support the effectiveness of the product.” Over the course of the three NDA submissions, Aldeyra has provided data from nine adequate and well-controlled clinical trials, five of which achieved all multiplicity-controlled primary endpoints, consistent with or greater than the success rates of clinical trials conducted for approved dry eye disease products.

Aldeyra Therapeutics Form 8-K, filed September 29, 2026

We are aware of two FDRRs in 2026 for ophthalmological drug products: one FDRR resulted in an Appeal Granted decision, and one FDRR is awaiting an advisory panel.