A major news story of
the past week was the emergency authorization from the Food and Drug
Administration (FDA) for use of the first COVID-19 vaccine, developed by Pfizer.
A second, similar vaccine from Moderna is expected to receive similar
authorization within the next day or so.
Not surprisingly, during these times of so much discord and distrust, a number of friends have asked me whether I have confidence in this vaccine. This question reminded me of my very first project when I joined Pfizer in 1992.
Tandospirone was in the class of drugs known as selective 5-HT1A receptor partial agonists. Some years earlier, the drug had been shown in clinical trials to be an effective anti-depressant, but its development was halted due to the high rate of troublesome side effects, particularly dizziness. In the early 1990s, it was reformulated using a new modality called the gastrointestinal therapeutic system (GITS), with the thought that this would eliminate, or at least reduce, the side effects. Because the FDA usually requires results from two trials to approve such indications, we conducted two identical clinical trials in patients with moderate depression. Patients were randomly assigned to receive either the active drug or a placebo in a double-blind fashion (neither the patients nor the treating physicians knew which one they were taking), and followed for 12 weeks, with assessments using commonly accepted measures of severity of depression, the primary one being the Hamilton Depression Rating Scale (Ham-D).
When all the patients had completed the twelve weeks of observation, the data was collected and the blind broken. When we plotted the change in Ham-D over time for each study, the graphs were basically two nearly horizontal lines right on top of each other: in other words, the patients treated with active drug were no better off than those who had received a placebo. Further, the rates of dizziness in the patients on the active arm remained unacceptably high.
When it came time to present these results to our Senior Management, the medical director on the project asked me to make the presentation. I suppose he did not want to be associated with this “negative” study. I, perhaps naively, saw it as a good chance to interact with Senior Management. When I finished my presentation, the head of the department said (I’m paraphrasing here, these were probably not her precise words), “I know these results are disappointing, but you set out to answer a question and you answered the question. You did a fine job.”
Granted that the stakes for this or any of the other compounds on which I worked were not nearly so high as with the coronavirus vaccine, but throughout my 20-year career in research in the pharmaceutical industry I was fortunate to work with devoted scientists and clinicians who truly did strive to provide the best for patients. I certainly recognize that pharmaceutical companies sometimes market their products in aggressive ways; it is a business, after all. But in the face of a global pandemic to which all of us are vulnerable, it is inconceivable to me that anyone has cut corners or been less than honest. It is clear from having watched the FDA advisory panel evaluating the Pfizer vaccine last week that there are still some unanswered questions. That is not surprising given the speed at which this study was designed, carried out, and analyzed. At the end of the day, the potential benefit of having vaccines is unquestionably enormous, and the risk relative to that benefit seems quite small.
As I was writing this, I wondered whether anything had ever happened with tandospirone. I typed it into Wikipedia and found this:
Tandospirone (brand
name Sediel) is an anxiolytic and antidepressant drug used in China and Japan, where it is marketed by Dainippon Sumitomo Pharma. It is a member of the azapirone class of drugs and is closely related to other
azapirones like buspirone and gepirone.
In an on-line search, I
also found this:
A group of researchers from Queensland
University of Technology, Australia has identified a drug that could
potentially help our brains reboot and reverse the damage caused by heavy
alcohol consumption.
This is the first time tandospirone has been
shown to reverse the deficit in brain neurogenesis induced by heavy alcohol
consumption. Tandospirone acts selectively on a serotonin receptor.
The researchers are constantly looking at new
treatment strategies for alcohol abuse and addiction, which is characterised by
extended periods of heavy alcohol use, binges and abstinence, and anxiety and
depression which contribute to relapse.
According to the researchers, this drug is
relatively new and available only in China and Japan. It is commonly used
there and shown to be highly effective in treating general anxiety and well
tolerated with limited adverse effects
Finally, thinking about this brought to mind my first project in the pharmaceutical industry, during the year I spent at Lederle Laboratories, where I worked on an HIV anti-retroviral drug known as FLT. The drug was in its first phase I study. We had enrolled maybe a dozen or so late-stage AIDs patients when, sadly, three of them died. The trial was halted. It was never 100% clear whether the deaths were due to side effects or simply due to lack of efficacy, but the development was halted. All I was able to find was a description of the trial on a clinical trials registry:
It was at that point that I happened to receive a call from a friend about a job at Pfizer, and the rest, as they say, is history. Thanks to my friend Sy for encouraging me to think and write about this.
So, will I take the vaccine? I am ready to roll up my sleeve as soon as I can!
Meanwhile, stay safe and well.
Love,
Rebecca
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