South Africa’s drug regulator terminated its controversial COVID-19 ivermectin program. The South African Health Products Regulatory Authority (SAHPRA) will no longer allow importation of unrecovered ivermectin products, nor can health facilities hold bulk ivermectin stock in anticipation of prescriptions for the unregistered products. The controversial “Section 21” approval program is gone, and with it, a piece of South African history. A moment in time when a diverse group of healthcare providers and advocates, civil society activists, and community health workers across the country pushed for low-cost, repurposed treatments in response to the pandemic is over. Culminating in a victorious lawsuit with bittersweet real-world implications, SAHPRA pounded the last nail in ivermectin’s COVID-19 coffin.
Background
TrialSite chronicled how ivermectin was used extensively in the African nation as an early care treatment for SARS-CoV-2, the virus behind COVID-19. Due to the explosion of use during the early stages of the pandemic, by late 2020, the South Africa Health Products Regulatory Authority (SAHPRA) made a draconian move banning its importation and use for COVID-19. Effectively criminalizing a generic drug used to eradicate river blindness in other parts of Africa, raids and arrests were made, including the raid of a hospital in Durban. The regulator’s position was that many illicit products were entering the market, creating a black market threatening the health and safety of the South African population.
Lawsuits and resistance in the form of organizing across the civil society intensified. By January 2021, SAPHRA announced controlled compassionate access to ivermectin for COVID-19 early care. But although the regulator accepted use, access was nearly impossible under “Article 21” as physicians had to apply for compassionate use each and every time, and tens of thousands of people needed the treatment.
A lawsuit ensued, as reported by TrialSite.
By March 2021, the regulator gave in and negotiated a settlement involving the African Christian Democratic Party (ACDP) and an activist group known as AFRI Forum. They authorized the use of ivermectin for COVID-19 as an off-label regimen.
However, as TrialSite chronicled, the victory for ivermectin proponents in healthcare and across civil society was bittersweet.
As it turns out, the ruling hinged the access to the source drug from within the country, which triggers a Section 21 clause, allowing the use of a particular version of ivermectin—a cream then registered with the country’s regulator. Doctors could then prescribe ivermectin without having to apply it to SAHPRA each and every time, but it would involve compounding for human use. Hence, the need for healthcare facilities to hold bulk stock.
While the ruling offered a legal pathway for prescribing physicians and pharmacists to compound ivermectin for purposes of treating COVID-19, the actual practicalities of compounding and distributing the medication at scale during a pandemic made pragmatic implementation challenging. But proponents celebrated as community action had effectively taken on and in some ways, was victorious over the State.
What’s the Rationale for Termination?
Applications for ivermectin were scarce since the summer of 2021. In fact, the agency wrote that since August 2021, no new applications for importation of unregistered ivermectin were received, plus they reported “a marked decline in the number of health facilities applying for permission to hold bulk stock.” Frankly, much of the illicit black-market use of ivermectin continued for the reasons mentioned earlier (e.g., difficulty of scaling the compassionate use terms).
In the regulatory agency’s recent press release, they sought to explain to the public the rationale behind the decision—summarized in bullet points. TrialSite provides a table with bullet points and some comments.
SAHPRA Rational for Termination
Comments
Studies that showed benefit of ivermectin have been retracted
This could be deemed misleading. A couple of studies were retracted, and important meta-analyses showcasing benefits were retracted by one journal, but there are still 84 studies conducted, the great majority showing positive results.
Key Meta-analysis by Hill et al. retracted
There are many questions about the Hill meta-analysis. Hill himself was very bullish on the drug, but the sponsors of the study, Unitaid, appeared to have changed the document to convey a less upbeat recommendation. Other meta-analyses authors stand by their work (e.g., Kory, Lawrie, etc.), but authorities don’t accept these latter meta-analyses.
Findings of two large studies don’t support use.
Data in TOGETHER, as acknowledged by study author Ed Mills does show potentially positive data. Critics point out flaws in TOGETHER, which have been published in TrialSite.
Two other national health organizations updated their guidelines now to include ivermectin.
SAHPRA doesn’t mention which organizations, but TrialSite recently reported that the NIH recently changed their guidance from a neutral stance to recommend only for clinical trials.
FDA cautions against use for COVID-19 except for clinical trials
TrialSite has chronicled questionable behavior from the agency in regard to this drug. While the agency’s mandated with protecting the public, did it meddle too much in the affairs of doctors and their patients? Doctors have always prescribed off-label with proper patient consent. The difference here was the pandemic and a level of top-down controls put in place. Was this an appropriate and acceptable action by the FDA? A lawsuit was recently filed by a few physicians targeting both FDA and HHS.
WHO only recommends for clinical trials
WHO’s behavior during this pandemic raises significant questions. The Uttar Pradesh situation, where a public health program embracing ivermectin as part of a home medicine kit, is a case in point. While WHO publicly praised the program (and its results), they omitted the treatments the Indian state’s public health agency embraced. A legal group in India sued the WHO because of this another behavior associated with ivermectin.
Following the Herd
Essentially, SAPHRA is merely falling in line with the FDA and other leading agencies such as EMA, etc. They declared, “SAHPRA is under duty to consider all the published data and the conclusions of the aforementioned reputable authorities,” thus leading to a lack of “equipoise.”
Plus, vaccines are now widely available, although only about 31% of the South African population is fully vaccinated, according to Our World in Data. Due to Vaccines, available antivirals (although they are expensive for much of the South African population), a lack of demand (which TrialSite predicted due to the cumbersome nature of the program), and the fact that the agency argues “there is no credible evidence to support a therapeutic role for ivermectin in COVID-19,” the program was terminated.
Not mentioned in any mainstream media in North America or Europe was the way a diverse array of human interests in South Africa—multiracial and multicultural across economic class and religious lines came together and advocated bottom up for low-cost available treatments during the pandemic. That organizing effort culminated in the program that SAHPRA just terminated.