South Africa has been making the news quite a bit of late as TrialSite just recently announced the South African Health Products Regulatory Authority (SAHPRA) updated its national COVID-19 guideline while that nation’s Department of Health recently criminalized in the import of the well-known, widely used antiparasitic drug for use off label to treat COVID-19. Even more recently, they introduced on their website the “SAHPRA’s Guidance on the Use of Ivermectin in the Prophylaxis or Treatment of COVID-19.” Again, while TrialSite suggested the criminalization of ivermectin importation was draconian, SAHPRA was commended by us for at least starting to pay attention to accumulating data derived from clinical trials around the world. TrialSite did note that they conveniently precluded most of the clinical trials in the meta-analyses from both the UK’s Dr. Andrew Hill and the U.S.-based Front Line COVID-19 Critical Care Alliance (FLCCC). This was interesting to say the least. For whatever reason, the analysis only used a small subset (4) of the clinical trials as we reported. Now SAHPRA has gone a step further in rationalizing their view. They offer some point of view backing their December 22 position declaring that there is no evidence that the drug should be considered as a treatment for the pandemic. Although we disagree with their point of view, the fact that this regulatory authority at least puts forth its argument and extends an open door for expedited review of any clinical data is more than most regulatory bodies at this point. Of course, another point of view is one of the mounting death tolls from this horrific pandemic. From this vantage, the fact that at least 16 randomized clinical trials, dozens of observational studies and major hospital case series point toward something positive, raises so many questions for any rational mind. With an accumulation of data that a low cost, well-known and widely used drug may actually help, wouldn’t governments want to quickly subsidize research to verify and capitalize on such fortune? As we reported yesterday, apparently some political parties in South Africa are interested in this drug as well. As the story unfolds, TrialSite will continue to offer updates. Ultimately, these decisions are as much guided by vested interests, money and politics as they are science. This has been very apparent in the United States as TrialSite has chronicled ongoing evidence pointing to the confluence of power, politics and drugs. How else could the impulse in America to quickly grant hydroxychloroquine an emergency use authorization only then to revoke; or the convalescent plasma decision where political pressure form an outgoing, and unhinged POTUS pressured the FDA into a decision the NIH was certainly questioning? What about the $13+ billion in taxpayer money going into just a handful of vaccine and novel monoclonal antibody development efforts? These are important, and TrialSite commends the pharmaceutical industry for incredible work accelerating some of these efforts but low cost, generic options should be just as important, especially now.
On to the SAHPRA decision making and justification.
What is a summary of the South Dec 22 decision?
SAHPRA noted on December 22 that “Ivermectin is not indicated nor approved by SAHPRA for use in humans. There is no confirmatory data on ivermectin available as of yet for its use in the management of COVID-19 infections. In terms of safety and efficacy, there is no evidence to support the use of ivermectin and we do not have any clinical trial evidence to justify its use.”
What did “The Essential Medicines List (EML) COVID-19 Sub-committee Rapid Review on Ivermectin” conclude on December 21, 2020?
SAPPRA noted that a sub-committee involved with their Essential Medicines List conducted a rapid review on the topic and determine the following conclusion that first the overall quality associated with the randomized controlled trials involving COVID-19 patients was “extremely low” and second from the subset of studies they selected, they concluded ivermectin was in fact “not superior to placebo in terms of viral load reduction or clinical progression.” They also concluded there wasn’t any evidence from these randomized controlled trials that the drug can reduce mortality rates.
What is their stance on the Andrew Hill ongoing meta-analysis highlighted by TrialSite?
TrialSite commends SAHPRA for taking the time to at least address meta-analyses from both Dr. Andrew Hill in the UK and the Front Line COVID-19 Critical Care Alliance (FLCCC) in the United States. As we have stated, few other regulatory authorities appear to delve into such detail.
The systematic review of the clinical trial data for the treatment of COVID-19 is led by Dr. Andrew Hill working for the University of Liverpool, sponsored by Unitaid, a global health initiative that collaborates with partners to help spur innovation to help prevent, diagnose and treat major diseases in low-and middle-income countries (LMICs). They remind us that the report hasn’t been published in a peer-review scientific journal.
SAPHRA reminds the reader that the data according to Hill shows a trend toward a conclusion that ivermectin could possibly be associated with faster time to viral clearance, shorter duration of hospitalization and higher rates of clinical recovery with somewhat improved survival rates.
However, they remind the reader that not only does the meta-analysis concludes that “additional randomized clinical trial data were needed to confirm clinical benefit in COVID-19 infections as well as define an optimized dosing regimen” but also that Hill identified a number of limitations that TrialSite also included here.
SAPHRA points to Hill’s own conclusion that “well designed clinical trials are required to provide sufficient scientific data for the use of ivermectin for the treatment of COVID-19.”
What About their position on the FLCCC meta-analysis and Hill’s combined?
SAHPRA again reviewed both Hill and FLCC and concluded that 1) based on their review of the studies, the overall quality of the randomized clinical trials are “poor and underpowered.” SAHPRA then declared that based on the “available randomized controlled trial evidence,” the drug “appears not to be superior to placebo in terms of viral load reduction or clinical progression” and as mentioned they don’t see any benefit in reduction in mortality; 2) the existing study variability in terms of size, out-patient, early hospitalization is too wide; 3) lack of uniform dosage; 4) because ivermectin has been trialed “with several other concomitant medicines (proven and unproven, either alone or in combination with other medicines)” hence limiting any conclusions; and 5) that the various authors themselves identify lots of the limitations identified by SAHPRA. They do comment that the regulatory organization “eagerly awaits” new data from three more clinical trials identified by Dr. Hill’s meta-analysis.
Does SAHPRA encourage ivermectin clinical trials in South Africa?
Yes. Although they acknowledge there have been no such applications as of yet, according to their recent posting, “SAHPRA encourages the submission of clinical trial applications designed to establish the safety and efficacy of ivermectin in the management of COVID-19 infections for both treatment and prophylaxis and commits to expediting their review.”
Is SAHPRA monitoring the current pipeline of Ivermectin trials?
What will it take for SAHPRA to authorize Ivermectin for use targeting COVID-19 (treatment or prophylaxis)?
They will seek peer-reviewed publications or data on the use of Ivermectin for the treatment of COVID-19 that they deem sufficient evidence. They would “consider enabling access to approved formulations of ivermectin intended for human use, including through Section 21 authorization, provided such a request is supported by evidence for the indication requested and is justified based on a risk assessment that includes safety and clinical efficacy data.”