NRx Pharmaceuticals, Inc. announced a strategic acceleration of its plans to develop a commercial form of NRX-100 (intravenous ketamine) to treat acute depression and suicidality, based on recent data cooperation agreements and on changes in the regulatory environment. As previously announced, the Company has signed a Data Sharing Agreement to gain access to the patient level (anonymized) data from a major Ketamine study in France (BMJ 2022; 376). The findings of this trial demonstrate a dramatic effect of intravenous ketamine in reducing acute suicidality and depression, particularly in patients with bipolar depression.

The findings of this trial confirm the results reported by Grunebaum and coworkers (Am J Psychiatry 2018;175:327) and numerous smaller trials. Two simultaneous and unexpected developments augment NRx's renewed focus on offering a commercial form of intravenous ketamine: A long-awaited trial of nasal ketamine for the same indication failed to meet its primary endpoints. The FDA issued a second warning letter on October 10, 2023 cautioning against the compounding of ketamine, which follows its February 16, 2022 warning letter regarding the compounding of nasal forms of ketamine.

Sequential warning letters of this nature are frequently followed by enforcement actions, particularly in the case of a DEA scheduled, dangerous drug, such as ketamine. Without an approved form of intravenous ketamine for acute suicidality, its benefits will only be available to patients able to pay cash for off-label treatment, because unapproved therapies are not suitable for insurance reimbursement. Moreover, FDA's clear position regarding the illegality of compounded forms of ketamine is likely to further limit access to what appears to be a lifesaving drug.

Although NRx has long held the belief that ketamine is not suitable as a long-term treatment for depression and suicidality because of its potential for neurotoxicity, addiction, and hallucination, the company has have long-recognized ketamine's unique ability to provide rapid remission from acute suicidality, provided a safe, oral drug can be implemented to maintain the life-saving effect. With the availability of what are now two clinical trials that demonstrate clinically-meaningful and statistically significant benefit of ketamine vs. both placebo and midazolam (active comparator), the company hope that a path to accelerated approval of NRX-100 (IV ketamine) as an agent for rapid reversal of suicidality as a prelude to long-term oral therapy can be identified.

Preliminary estimates of this regulatory focused work show that this effort is within the company's current budget.