Israeli company offers new hope for treating severe depression

Dr Jonathan Javitt photo|: Alon Ron

NeuroRX, run by brothers Jonathan and Daniel Javitt, is based on research spurred by a close friend's suicide.

Columbia University last week published data about a trial with eight patients suffering from clinical depression that is resistant to drugs. The global media gave extensive coverage to the trial, although with mixed feelings. Some talked about the potential for a breakthrough in treatment of depression, while other claimed that the trial was too small and the celebrations premature. In any case, both the professional journals and the mainstream press reported the story mainly because it involved ketamine. This material, used in combination with other drugs, is one of the promising solutions in the treatment of depression.

A combination of three drugs

The trial included a combination of a number of drugs: ketamine, known as a recreational drug and anesthetic used primarily by veterinarians; an old drug for tuberculosis no longer in common use, and an anti-psychotic drug.

The trial is being conducted independently by Columbia University, but NeuroRX, a company recently founded by brothers Jonathan and Daniel Javitt, holds a patent for the combination of the three materials. The company was incorporated in Delaware, and the parent company is currently located in Israel.

Although the trial was conducted in an academic framework without any involvement by the brothers, it in effect proves the technological feasibility of the company's drug. It is likely to lead the company to a broader Phase IIb trial on a US Food and Drug Administration fast track designed for registration of new combinations of existing drugs.

If all goes well, Jonathan Javitt said in a "Globes" interview, the product is likely to reach the market within 4-5 years.

Jonathan Javitt is currently in the middle of immigrating to Israel, joining his brother Daniel, who came several years ago. Jonathan is an expert heath consultant for public institutions and drug companies, and the founder of a number of medical information companies sold to other parties, such as medical equipment company Siemens and insurance companies Aetna and United Insurance. He is also a part-time venture partner in Israeli venture capital fund Pontifax.

Several years ago, one of Javitt's close friends committed suicide as a direct result of bipolar disorder. "His case was classic," Javitt says. "He suffered from deep depression and suicidal thoughts. Many depressives suffer from suicidal thoughts, but also from inertia, meaning that they are unable to summon enough energy even to carry out their planned suicide. Sometimes, when they are treated with drugs, the energy and motivation aspect is 'treated' before the negative and suicidal thoughts disappear. These drugs are therefore liable to increase the danger of suicide.

"That's exactly what happened to my dear friend. He went back to the doctor, and said that Zoloft didn't work, that his thoughts were still negative. So they tripled the dosage, and that's what gave him the energy to carry out his suicide plans."

Javitt says this incident caused a turnaround in his attitude towards depression. "I once thought that these people could have made a different decision in their lives, but I now realize that it's not so simple."

Psychotic attacks

Several decades earlier, in the 1980s, Daniel Javitt, Jonathan's brother, began researching the effect of a drug called angel dust (PCP) on the brain.

The hospital in which he worked, Albert Einstein Hospital in Philadelphia, was in exactly the same area in which the phenomenon began, and many patients came to the young doctor with psychotic attacks that continued for many months, long after the drug itself was no longer in the body.

Daniel's advisor told him to research what exactly this drug was doing to the brain, which led to Javitt becoming a partner in the discovery of the NDMA receptor in the brain, which is apparently essential to the control of moods and thought patterns among various types of patients with depression and among healthy people as well.

Over the years, Daniel Javitt researched various ways of activating and deactivating the NMDA receptors in the brain, and their effects, and also continued this as a researcher at Columbia University.

After the death of Jonathan Javitt's friend, he told his brother that it was time to put the program into action. Daniel Javitt proposed founding a company that would test the combination of the three drugs (none of which was the psychotic drug angel dust, even though it was the basis of the discovery).

The first of the three, ketamine, blocks the receptor, thereby providing immediate relief from depression, but its effect lasts only 4-7 days, and is liable to be accompanied by psychotic attacks.

The second drug, D-Cycloserine, is a drug for treatment of tuberculosis, which also blocks the NMDA receptor. It begins operating a little later, but blocks the receptor for a longer period, without psychotic attacks or nightmares.

The third drug, Lurasidone, operates on a different receptor. It reduces psychotic attacks, and apparently contributes to the activity of Cycloserine.

Jonathan Javitt says that one of the next challenges will be finding the right dosage of Cycloserine for the trial, since a low dosage encourages the NMDA's activity (and is therefore liable to exacerbate depression) - only a higher dosage blocks it - a course of action that is not easy to provide in a clinical trial.

The result of the small trials conducted at Columbia University on eight patients with bipolar disorder showed 50% remission of depression and 75% in suicidal thoughts. The good results appeared within a few hours and lasted for several weeks. There was no control group for the trials.

The great hope

The reason that the company's treatment is causing such a stir is apparently the use of ketamine, currently considered the great hope for treatment of both depression and bipolar disorder. Johnson & Johnson has developed a ketamine inhaler aimed at providing immediate (but temporary) relief of depression. According to the company, the remission is likely to remind patients suffering from depression what it means to feel good, to give them hope, and help them persist in longer treatment that requires time for being adapted to the patient and several more weeks before it becomes effective.

Another company, Naurex, has developed a molecule similar to ketamine, which also acts on the NMDA receptors.

"They're trying to make 'a more pleasant ketamine, but they're on a long drug development track. That means that it probably will take them 8-9 years, a timetable that's completely different from ours," Jonathan Javitt says.

Naurex recently raised $80 million on the basis of its Phase II results. Both large companies like AstraZeneca and younger companies have conducted trials (unsuccessfully) with ketamine derivatives.

NeuroRX is not yet disclosing how much money it has raised, but Jonathan Javitt says, "We have all the seed money we need." The company raised money from biomedical people, including Chaim Hurvitz, son of the late Teva Pharmaceutical Industries Ltd. (NYSE: TEVA; TASE: TEVA) chairman and CEO Eli Hurvitz. Chaim Hurvitz is listed as one of the company founders.

Jonathan Javitt: "Eli Hurvitz was a close friend of mine, one of the great friendships in my life. That 's also how I came to invest in the Pontifax fund." He added, "I brought the best investors I know to the company, and so far, none of them has said no to me."

Published by Globes [online], Israel business news - www.globes-online.com - on July 1, 2015

© Copyright of Globes Publisher Itonut (1983) Ltd. 2015

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Dr Jonathan Javitt photo|: Alon Ron
Dr Jonathan Javitt photo|: Alon Ron
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