Every second of every day, someone in the world attempts suicide.

NRx Pharmaceuticals is developing a drug for people whose suicidal thoughts stem from bipolar depression, the low mood phase associated with the severe mood swings of bipolar disorder.

If clinical trials proceed as planned, the company hopes to bring the drug to market in 2024.

Although bipolar depression accounts for only about 10 percent of all people with depression, it accounts for about 40 percent of those who try to harm themselves, says Dr. Jonathan Javitt, founder and chief scientist of NRx, the publicly traded company. Nasdaq which merged with NeuroRx in 2021.

Suicidal bipolar depression is a devastating disease and one that has not been addressed by pharmaceutical companies. Today, there are no FDA-approved medications for people with suicidal bipolar depression.

NRxs multi-patented NRX-101 (Cyclurad) combines two FDA-approved pharmaceuticals: the tuberculosis drug D-cycloserine and the anti-infective drug lurasidone. It is meant to be taken orally at home.

Most conventional antidepressant drugs that can actually increase the risk of suicide target the serotonin pathway in the brain. NRX-101 acts on the NMDA receptor in the brain, a recently validated target for the treatment of suicidal ideation and depressive symptoms, particularly in bipolar depression.

A study conducted at the Herzog Hospital in Jerusalem showed a significant benefit of D-cycloserine (versus placebo) in patients with treatment-resistant depression. And the effect of D-cycloserine in reducing suicide was demonstrated in an independent study in 2019.

The drug candidate NRxs is also useful after an injection of the anesthetic drug ketamine, which reverses depression but only for about four days. Ketamine cannot be administered continuously because it causes psychedelic, addictive, and neurotoxic side effects. NRX-101 sustains the antidepressant effect of ketamine for two months without these unwanted side effects.

Duration of the search

Javitt, an ophthalmologist by training, has led drug development programs for eye disease and diabetes for the past 40 years with Allergan, Eyetech, Merck, Novartis, Pfizer and Pharmacia.

But the research that served as the foundation for NRx’s drug candidate began with his brother, Daniel, a Jerusalem-based psychiatrist.

Early in my brother’s career in the 1990s, he set out to figure out why a drug of abuse called angel dust causes acute psychosis. He found it’s because angel dust binds to the NMDA receptor in the brain, says Jonathan Javitt.

It followed ongoing research in this field, including Dr. Robert Berman’s discovery that drugs that bind to the NMDA receptor can profoundly relieve depression and suicidal thoughts.

Daniel has become one of the most published authors in this field of brain science, says Javitt. What we are doing is a natural consequence of that life of research.

Herzog Hospital, where the first clinical trial of NRX-101 was conducted, is a founding shareholder along with people including Chaim Hurvitz, a former director of Teva and president of Teva International Group.

Commercialization in 2024

When ISRAEL21c first wrote about the newly formed company in 2015, the idea that an NMDA-antagonist drug could treat symptoms of depression was new.

It’s now a well-validated idea, says Javitt. There are drugs in development, two approved by the FDA, so the science has been well accepted.

The company’s progress on the psychiatric drug, however, was sidelined for about three years during the pandemic, when NRx was working with the Israel Institute for Biological Research on Covid-related developments.

The NRX-101 program got back on track about a year ago.

We are still the only company focused on bipolar depression and especially suicidal bipolar depression, Javitt tells ISRAEL21c.

Headquartered in Delaware, NRx completed an initial Phase II study that resulted in a breakthrough therapy designation from the FDA and a special protocol agreement.

We’re now in a recording study of people with suicidal bipolar depression, Javitt says.

He notes that this is the first known study of a new antidepressant that successfully enrolled patients with active suicidal ideation.

We expect to finish by the end of the year and have already completed our production scaleup to be ready for commercialization. We aim for FDA approval to release the drug to market in 2024.

The same drug is also being tested to prevent suicidal ideation in cases of PTSD and chronic pain in depression.

After 9/11, we’ve lost four times as many [US military] veterans and servicemen to suicide rather than combat, notes Javitt, who has served as health adviser to four White House administrations.

NRx estimates the market potential for a treatment for bipolar depression at $2.2 billion, given that approximately 7 million people are bipolar and 9-10% of them experience suicidal thoughts.

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