FDA Filing Fee Waiver for New Drug Application of NRX-100 for Suicidal Depression

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NRx Pharmaceuticals announced the grant of a filing fee waiver by the US Food and Drug Administration (FDA) to exempt NRx from a $4.3 million fee to file its New Drug Application for preservative-free ketamine (NRX-100). NRX-100 is a preservative-free formulation of intravenous ketamine for acute suicidal crises in depression.¹

"We at NRx are encouraged by this important fee waiver from the FDA and by the posture expressed by the new leadership of the Department of Health and Human Services in support of new psychedelic drugs to treat the more than 3 million Americans who consider suicide every year and currently have no approved treatment other than electroshock therapy," said Dr. Jonathan Javitt, CEO and Chairman of NRx Pharmaceuticals. "NRx aims to make its preservative-free ketamine available to physicians who care for patients with suicidal depression."

NRx will submit data from controlled clinical trials that demonstrate ketamine to be superior to both a placebo and an active comparator. Additionally, the company will seek to prove NRX-100 is superior to electroshock therapy in treating various forms of depression, including in patients with active suicidal ideation.

NRX-100 offers a “preservative-free” formulation. Currently available forms of ketamine contain the preservative benzethonium chloride, but its safety for repeated use has never been demonstrated. In fact, the preservative was added back in the 1970s when ketamine was originally formulated as an anesthetic, and although benzethonium chloride has not demonstrated toxicity in anesthesia, the class of preservatives has been shown to be neurotoxic and cytotoxic to eye tissue when incorporated in eye drops.² NRx-100 has now demonstrated stability and sterility for more than 2 years of shelf life.

Also important to note is accessibility. Although ketamine is increasingly being used for treatment-resistant depression and related disorders,³ it is only FDA-approved for use as an anesthetic and is not reimbursed by most insurance carriers for treatment of major depressive disorder or suicidality. By applying for FDA approval to treat suicidal depression with NRX-100, NRX hopes to make this therapy available to all Americans seeking treatment and not just those who can pay out of pocket.

NRX-100 was initially granted Fast Track Designation by the FDA in 2017 for use in combination with NRX-101 (D-cycloserine/lurasidone) for treatment of acute suicidality in bipolar depression.⁴ Today’s waiver, granted at the discretion of the FDA to Small Business Entities and for drugs that are deemed to be necessary for public health, could enable the completion of NRX’s New Drug Application for NRX-100. The NDA filing is anticipated by the end of the second quarter of this year.

References

1. NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) Announces FDA Award of Filing Fee Waiver for Upcoming NRX-100 (preservative free ketamine) New Drug Application to Treat Patients with Suicidal Depression. News release. FirstWord Pharma. May 1, 2025. https://firstwordpharma.com/story/5955621

2. Goldstein MH, Silva FQ, Blender N, et al. Ocular benzalkonium chloride exposure: problems and solutions. Eye (Lond). 2022;36(2):361-368.

3. Bender K. Slow-release oral ketamine formulations show promise for at-home treatment of resistant depression. Psychiatric Times. September 4, 2024. https://www.psychiatrictimes.com/view/slow-release-oral-ketamine-formulations-show-promise-for-at-home-treatment-of-resistant-depression

4. NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) files initial section of U.S. New Drug Application to the FDA for NRX-100 (IV ketamine) for the treatment of suicidal depression. News release. December 30, 2024. https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-inc-nasdaqnrxp-files-initial-section-of-us-new-drug-application-to-the-fda-for-nrx-100-iv-ketamine-for-the-treatment-of-suicidal-depression-302340035.html