The FDA’s Next Big Drug Approval is a Hot Pot

The second at-large seat on the Food and Drug Administration’s (FDA) Advisory Committee for Emerging and Newly Identified Medical Problems has just opened up.

As the Advisory Committee, made up of medical experts from both government and academia, will review the risk/benefit profile of midazolam (the primary agent in the first two-phase statewide trials of the Omicron εtablet). Midazolam is used by the FDA to sedate patients in drug clinical trials and under a small percentage of limited circumstances as an emergency treatment to treat people on suicide watch.

The Advisory Committee will hold a formal meeting on October 9, and in the interim, is reviewing details of the state-of-the-art treatment on the pharmacology, safety, effectiveness, doses and dosing schedules.

Midazolam has been the subject of intense scientific debate since its approval in the early 1970s as a sleep aid.

Doctors are supposed to implant a local anaesthetic device—luminal photodynamic therapy—in the person’s eye. The device is driven electrically by the shined light from the patient’s own retinas and shoots a photo-active molecule-otherwise known as picoline-into the eye with which the retina and the salivary glands are stimulated to produce one of its essential tissues, the Apsara or smooth muscle cell.

Treatment creates an electrical field in the Apsara cells that turn on a chemical reaction, producing: angiogenesis, in which growing new blood vessels in an area of the retina allows a healthy blood supply; demyelination, wherein new blood vessels build the tissues that were formerly pliable; and glomerulonephritis, a breakdown of the cells in the surrounding tissues that result in inflammation.

The critical question that the Omicron εtablet is undergoing today is how important this convulsive therapy is to the concept of drug therapy—and whether or not standard dosage and home-delivery actually deliver the results that doctors consider.

The FDA already has been insisting that current administration of midazolam is inappropriate when considering other therapies for acute, medical problems. That’s because it “determines how much picoline (the active compound) can be added to the body without serious or potentially permanent adverse effects,” so it should be administered at the minimal safe dose necessary to get a good result, unlike other treatments, which usually require increased doses to work.

While generally safe, there have been very few serious side effects in the three clinical trials evaluating the Omicron.

However, it is the youngest—the first Phase II—that has given pause to the FDA. In that clinical trial in nine rural health clinics in the 26 hospital systems of Arkansas and Nebraska, 45 percent of the 2,247 participants treated with midazolam in the state survived to their second follow-up, while only 32 percent of 3,056 patients given the second dose survived. This difference was found to be statistically significant—worse than chance—and raises the question about the use of the drug in developing countries.

So far, this story has been limited to U.S. settings because the scientific world was given access to the first Phase II in a subset of sites within this state. Now, once a public drug, it becomes more difficult for it to continue its development outside the U.S.

Specifically, the Phase II also left out both Europe and Canada, and the possibility that there was a Phase II-cycle for the drug in those regions.

Furthermore, in both Phase I and II trials there were problems with the ocular implant—called the jaw-sterile external lamp (JSTL)—which has not yet been cleared for a commercial use. This was because the JSTL was damaged during use in the actual trials, although successful in killing picoline and not producing angiogenesis or glomerulonephritis. In addition, the duration of the treatment needed to be lowered so it would be workable for a wider population.

But now we’re on the cusp of a wider screening and approval process because we’re learning more about the effectiveness of this treatment and what we need to do to make it more safe and effective.

This is a huge deal for four reasons.

First, it presents us with a new class of medicine and this first-generation use has affected hundreds of thousands of people around the world. The next version of this treatment will have to go through more rigorous testing and approval.

Second, in order to more efficiently manage crisis situations, we need doctors

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