President Donald Trump has not officially given his support (“Is this something that people are talking about very strongly? We will see it. We will see,” he told a reporter last week.)
Plain old oleandrin, the non-proprietary botanical product, first appeared in the medical literature in 1949 with a study of its effect on chick embryo hearts, then, five years later, as a possible treatment for human heart problems.
Many reports have focused on the apparent toxicity, which has led to accidental – and sometimes deliberate poisonings, including to suicide. It has also poisoned animals. Consider an article from July 2020 entitled: “Outbreak of Oleander (Nerium oleander) Poisoning in Dairy Livestock: Implications for Clinical and Food Safety” from the Swiss journal Toxins.
In fact, it is the toxicity of both the Nerium oleander plant and its extract, rather than its effectiveness, that dominates the published scientific literature, as well as a leading guide to botany.
On the therapy side, published, peer-reviewed literature on oleandrin is almost all lab-based, non-clinical, providing an initial focus on heart disease to neurological conditions and various cancers, including melanoma, osteosarcoma (a bone cancer), and pancreatic cancer.
The clinical experience in pancreatic cancer and “refractory solid tumors” includes about 100 patients, the only human recipient I have identified in the published literature. One early trial examined toxicity in 18 patients; another in 46 patients.
Next, to investigate possible effectiveness, it was studied in 42 people with advanced pancreatic cancer. In this experiment, the proprietary extract of Nerium oleander showed no benefit but caused a lot of toxicity. Per the investigators, grade three and above “treatment-induced adverse events” (on a scale of one to five, where grade three is a serious adverse event and five are deaths) were seen in 63.2% of patients.
Despite this, the authors, who Drs. Robert Newman, Chief Science Officer of Phoenix Biotechnologies Inc., listed the study medication as “generally well tolerated.” The drug was not further developed for treatment of this cancer.
Another trial, registered at Clinicaltrials.gov in 2012, would be given to patients with lung cancer at MD Anderson Cancer Center. However, the study was withdrawn; no details have been published as to why.
Undiscouraged, Phoenix Biotechnologies, Inc., broadened the scope. The assessment that the combination reaches high levels in the brain has led to consideration of its use for stroke, Parkinson’s disease and other neurodegenerative conditions, such as brain cancers. No clinical data have been published for this theoretical use.
Oleandrin (both the proprietary extract and other formulations) has been studied over the years in the lab for various viral infections, including HIV, hepatitis C, and possibly Marburg virus and Ebola virus.
Most recently, however, a non-peer-reviewed lab study described the results of oleandrin (not described as its own product, although it involved Dr. Newman of Phoenix Biotechnology, Inc.), showed (like many other chemicals) suppression of the coronavirus that causes Covid-19.
Given the absence of other available information, this non-clinical work seems to drive the enthusiasm for oleandrin among these pharmaceutical directors and directors. Whitney, of Phoenix Biotechnology, Inc., claims to have seen “compelling” data – that he can not share, suggesting that additional companies are familiar with the company.
It is unclear whether that enthusiasm was dampened by a recent report that the U.S. Army Institute of Infectious Diseases conducted tests on the effect of oleandrin on Covid-19, which were stopped because of “indecisive” results.
Without question, the proprietary extract of Nerium oleander has a much weaker argument for use in treating Covid-19 than hydroxychloroquine, which came under fire and promoted Trump to a similar non-peer-reviewed list with results in 20 patients.
We have no results from the proprietary extract of Nerium oleander in human Covid-19 infection, only a sobering record of toxicity and therapeutic failure in other diseases.
Plus, as a general rule, any drug that “shows promise” for so many different conditions – heart disease, stroke, Parkinson’s, various cancers, HIV, hepatitis C and now Covid-19 – is probably not all that it’s cracked up to be. It is the pharmaceutical equivalent of a dilettante.
The logical and above next step is to study the proprietary extract of Nerium oleander in well-designed clinical trials.
Unfortunately, the current human trial of the drug to treat and prevent Covid-19 announced by HealthQuilt, a large primary care network in Houston, is a “helter-skelter” study with a non-randomized “parallel assignment” of outpatients.
This means that participants will receive the proprietary extract of Nerium oleander as no proprietary extract of Nerium oleander. The 100 participants will include both those with proven infection and those without infection who have recently been exposed to an active case.
Unlike all clinical trials in which I am involved or read about, these study participants may “choose” or “not choose” if they want to take the proprietary extract of Nerium oleander, which are given four times in this trial under the tongue a day for five days.
Allowing participants to choose whether or not to receive treatment will run counter to a basic principle in clinical trials: the use of randomization to eliminate potential biases in outcomes.
A HealthQuilt spokesman told CNN, “This was never designed as a randomized study – this was just a feasibility study so we could collect the data.”
He added that the company, which looked at the extract of Nerium oleander as a supplement that could potentially stimulate the immune system – not whether it was a cure or treatment for Covid-19 – would suggest a double-blind randomized study. only if the data from the helter-skelter study are supported.
No information on specific safety measures is mentioned and the data commission charged with overseeing the progress has been housed at the Schull Institute, a small, private foundation in Houston founded in 2001 by geneticist Dr. Jack Schull.
Through their website, they appear to be largely focused on mentoring young leaders in science and medicine. Daniel Twiddy, vice president of the Schull Institute, told CNN that since 2019, the foundation has overseen clinical trials and organization of institutional review boards (IRBs).
Another very unusual element of this study is that the lead researcher for the trial and CEO of HealthQuilt, Dr. Kimberly Dunn, also named as the president of the Schull Institute.
The approach of the same person as a group to lead a study and to be involved in the company that has the task of controlling the security of that study is unique in my experience, given the potential for conflict of interest.
The National Institute of Allergy and Infectious Diseases (NIAID) has guidelines for clinical study behavior and explicitly states that a group of experts, independent of the experimental researchers and others involved in the study, should conduct the trial periodically review to ensure patient safety.
The HealthQuilt spokesman said that Dr. Dunn had plans in March to transfer the presidency of the Schull Institute, but that was delayed due to the coronavirus. She has withdrawn from any discussion of the board’s study, he told CNN, an action that was also noted by Mr Twiddy.
Strictly from the perspective of a study methodology, this is a poorly designed trial. As a feasibility study, the intention is not to focus on scientific rigor, but rather on the practical question of whether a research site can handle the cumbersome and complicated specifications of actually doing a test.
Meaningful information, other than feasibility, should never emerge from such a study.
But the purpose of the trial, I think, is not a generation of useful clinical information, but rather to get a little hint that suggests that maybe, just maybe, the proprietary extract of Nerium oleander can help against mild Covid-19 .
With that wispy “recommendation,” we’ll probably see hydroxychloroquine redux, with a carnival of talking heads hawking it and fresh pressure on the FDA for some sort of approval.
Whether or not the FDA hopes under such pressure does not matter much. The real game here is not whether the proprietary extract of Nerium oleander actually works.
The HealthQuilt spokesperson said, “What anyone does with the data is out of our hands … We never intended to get politics or anything else, and we certainly do not consider this a cure or treatment, but we are just the track data and see where it goes from there. “
No, after witnessing the anti-regulatory zeal of many of those in the administration, my concern is that they are using the Covid-19 crisis as an opportunity to further regulate medical safety calling, which the administration’s recent decision no longer requires premarket review for particular lab test has only been tightened.
And drug approval is a great goal: the scientific enterprise is a deliberately slow and cautious process that relies on cold, hard data to ensure human safety.
How easy it is to deceive those who believe in science into nasty and useless fuddy duddies that move at a rotating speed dial. There are so many sick and dying people and all they want to do is study the problem (go think this).
Typical bureaucratic answer! Or as Whitney jokingly says, “you know (they emphasize) you must have years of study, and you must have this, that, and the other, and so forth.” Note that the administration has leaked the recent Russian Covid-19 vaccine if it lacks sufficient safety data.
Better to go blindly with the MyPillow boy in a utopian regulatory environment where the motto is “what do you have to lose?” To which I would respond, the reported toxicity of oleandrin in humans, “saw your health.”
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