Kent Sepkowitz is a CNN medical analyst and a physician and infection control expert at Memorial Sloan Kettering Cancer Center in New York. The views expressed in this commentary are his own. View more opinion at CNN.
President Donald Trump has not officially given his support (“Is it something that people are talking about very strongly? We’ll look at it. We’ll look at it,” he told a reporter last week.) But Mike Lindell, the CEO of MyPillow and chairman of the Minnesota Trump campaign, pronounced the President “enthusiastic” about the unproven therapeutic. Lindell said he hoped the Food and Drug Administration (FDA) would consider its approval soon if not sooner. Dr. Kent SepkowitzThe source of all the headlines is a proprietary extract of oleandrin developed by Phoenix Biotechnology, Inc., a company in San Antonio, Texas. The product has been around for almost 20 years and has been referred to by many names including Anvirzel, PBI-05204, oleandrin and “proprietary extract of Nerium oleander,” the moniker used in the product’s first clinical trial against Covid-19 infection and the term I will use. (Because of the proprietary nature of the product, it is not possible to know if these substances are chemically similar or actually identical.)Mr. Lindell is new to Phoenix’s board of directors — he was added last week, receiving a financial stake in the company — and his upbeat attitude about the proprietary extract of Nerium oleander is shared by company Vice Chairman and Director Andrew Whitney who is “100%” behind the claim that the product cures Covid-19 in 2 days. Read MorePlain 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 its considerable toxicity, which has led to accidental — and sometimes deliberate poisonings, including for suicide. It has also poisoned animals. Consider a July 2020 article titled: “Outbreak of Oleander (Nerium oleander) Poisoning in Dairy Cattle: Clinical and Food Safety Implications” from the Swiss journal, Toxins.For Trump, false claims go way backIndeed, 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 botanicals. On the therapy side, published, peer-reviewed literature on oleandrin is almost all lab-based, not clinical, and careens from an initial focus on heart disease to neurologic 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 recipients I have identified in the published literature. One early trial examined toxicity in 18 patients; another in 46 patients. Next, to examine possible effectiveness, it was studied in 42 people with advanced pancreatic cancer. In this trial, the proprietary extract of Nerium oleander demonstrated no benefit but did cause a great deal of toxicity. Per the investigators, grade three and higher “treat-emergent adverse events” (on a scale of one through five, where grade three is a severe adverse event and five is death) were seen in 63.2% of patients. Despite this, the authors, who included Dr. Robert Newman, Chief Science Officer of Phoenix Biotechnologies Inc., called the study drug “generally well tolerated.” The drug was not developed further for treatment of this cancer. Another trial, registered at Clinicaltrials.gov in 2012, was to 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 its scope. The observation that the compound reaches high levels in the brain has led to consideration of its use for stroke, Parkinson’s disease and other neurodegenerative conditions, as well as brain cancers. No clinical data has yet been published for these theoretical uses.Rushing a Covid-19 vaccine before we get full data would be an enormous mistake Oleandrin (both the proprietary extract and other formulations) also has been studied in the lab for various viral infections through the years, including HIV, hepatitis C, and possibly Marburg virus and Ebola virus. Most recently, though, a non-peer-reviewed lab study described the results of oleandrin (not described as the proprietary product though involving Dr. Newman of Phoenix Biotechnology, Inc.), demonstrating (like many other chemicals) suppression of the coronavirus that causes Covid-19. Given the absence of other available information, this nonclinical work appears to be driving the enthusiasm for oleandrin among these pharmaceutical directors and executives. Whitney, of Phoenix Biotechnology, Inc., claims to have seen “compelling” data — that he is unable to share, suggesting additional results are known to the company.It’s unclear whether that enthusiasm has been dampened by a recent report that the US Army Institute of Infectious Diseases conducted tests on oleandrin’s effect on Covid-19, which were halted due to “inconclusive” results.Without question, the proprietary extract of Nerium oleander has a much weaker argument for use to treat Covid-19 than hydroxychloroquine, which caught fire and Trump promoted after a similar non-peer-reviewed listing showing results in 20 patients. We have no results of 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 — probably isn’t all it is cracked up to be. It’s the pharmaceutical equivalent of a dilettante.The logical and aboveboard 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 that has been announced by HealthQuilt, a large primary care network in Houston, is a “feasibility” study with a non-randomized “parallel assignment” of outpatients.This means that participants will receive either the proprietary extract of Nerium oleander or no proprietary extract of Nerium oleander. The 100 participants will include both those with proven infection and those without infection who have been recently exposed to an active case. What good is a vaccine if Americans won't roll up their sleeves?Unlike any clinical trials I have been involved with or read about, this study allows participants to “elect” or “not elect” whether they want to take the proprietary extract of Nerium oleander, which in this trial will be given under the tongue four times a day for five days. Allowing participants to elect whether or not to receive the treatment runs counter to a bedrock principle in clinical trials: the use of randomization to remove potential bias in results. A spokesperson for HealthQuilt told CNN, “This was never designed as a randomized study — this was just a feasibility study so we can collect the data.” He went on to add that the company, which was looking at the extract of Nerium oleander as a supplement that could potentially boost the immune system — not whether it was a cure or treatment for Covid-19 — would suggest conducting a double-blind randomized study only if the data from the feasibility study supported moving forward.No information on specific safety measures is listed and the data monitoring committee that is charged with overseeing the progress is housed at the Schull Institute, a small, private foundation in Houston founded in 2001 by geneticist Dr. Jack Schull. Per their website, they appear largely focused on mentoring of young leaders in science and medicine. Daniel Twiddy, vice president of the Schull Institute, told CNN that the foundation has been overseeing clinical trials and organizing institutional review boards (IRB’s) since 2019. Another extremely unusual element of this study is that the principal investigator for the trial and CEO of HealthQuilt, Dr. Kimberly Dunn, also is listed as the president of the Schull Institute.The approach of having the same person or group lead a study and be involved with the company tasked with monitoring the safety of that study is unprecedented in my experience, given the potential for conflict of interest.The desperate 'pandemic' among US veteransThe National Institute for Allergy and Infectious Diseases (NIAID) has guidelines for clinical study conduct and explicitly states that a group of experts, independent of the trial investigators and others involved in the study, should periodically review the conduct and results of the trial to assure patient safety.The HealthQuilt spokesperson said Dr. Dunn was scheduled to transfer the presidency of the Schull Institute in March, but that was delayed as a result of the coronavirus. She has recused herself from any discussion of the study from the board of directors, he told CNN, an action also noted by Mr. Twiddy.Strictly from a study methodology perspective, this is a poorly designed trial. As a feasibility trial, it is intended to focus not on scientific rigor but rather on the practical issue of whether a study site can handle the laborious and complicated specifics of actually doing a trial. Meaningful information, other than feasibility, should never arise from such a study.But the goal of the trial, I suspect, is not generation of usable clinical information but rather to get a tiny hint that suggests that maybe, just maybe, the proprietary extract of Nerium oleander can help against mild Covid-19. With that wispy “endorsement,” we are likely to see hydroxychloroquine redux, with a carnival of talking heads hawking it and fresh pressure on the FDA for some sort of approval. Whether the FDA caves or not under such pressure doesn’t much matter. The real game here is not whether the proprietary extract of Nerium oleander actually works.The spokesperson for HealthQuilt said, “What anyone does with the data is out of our hands… We never intended to get political or anything else, and we’re certainly not touting this as a cure or treatment, but we’re just following the data and seeing where it goes from there.”No, having witnessed the anti-regulation fervor of many of those in the administration, my concern is that they are using the Covid-19 crisis as an opportunity to peel away even more drug safety regulations, which the recent administration decision to no longer require premarket review for certain lab test has only sharpened. Get our free weekly newsletter
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And drug approval is a great target: the scientific enterprise is a deliberately slow and cautious process that depends on cold, hard data to assure human safety.How simple it is to miscast those who believe in science into annoying and useless fuddy-duddies moving at a rotary-dial phone pace. There are so many sick and dying people and all they want to do is study the problem (goes this thinking). Typical bureaucratic response! Or as Whitney says derisively, “you know (they insist) you need to have years of studies, and you need to have this, that, and the other, and so forth.” Never mind that the administration denounced the recent Russian Covid-19 vaccine as lacking sufficient safety data.Better to move blindly forward with the MyPillow guy in a utopian regulation-free environment where the watchword is “what have you got to lose?” To which I would respond, considering oleandrin’s reported toxicity in humans, “your health.”
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