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Ivermectin has been approved for use in treating Covid-19 in South Africa on a limited basis. This follows an urgent court application by lobby group AfriForum to force the regulatory authority to allow the use of the drug most commonly used for treating parasites in animals in the country for human use. First, you will hear Professor Helen Rees, chair of the SA Health Products Regulatory Authority (SAHPRA) board, explain why the regulator cannot give full registration to the drug for human use in relation to Covid-19. SAHPRA CEO Boitumelo Semete-Makokotlela sets out more detail on how access to the drug will work and next steps as a university works on approval for a human trial on the use of Ivermectin to treat Covid-19. They were speaking to journalists at the Pretoria Press Club. – Jackie Cameron
“The Drug Regulatory Authority SAHPRA has been in existence now since the beginning of twenty nineteen and a drug regulatory authority’s primary responsibility is about the safety, quality and efficacy of health products of all health products. So that’s why it includes, for example, vaccines. But we also take into account when we think about the benefit risk, we take into account the national context in which we’re operating and working. But it’s a very strongly evidence based response that comes from the Drug Regulatory Authority … We’ve looked at lots and lots of clinical trials, credit to the researchers of this country. People have really been pushing through clinical trials to the regulator. We’ve had a dedicated committee that’s really looked at this and fast tracked that.” said Professor Reese.
“I think we all appreciate in the midst of an emergency, which we’re in, in the midst of… the pandemic, there are things that will present to the regulator that are not necessarily in the routine course of business where the regulator really has to think very hard and think of the context in which they’re working while still absolutely adhering to the issue of ensuring safety, quality and efficacy. So that is the balance. There is such a lot of understandable concern, emotion, questions about Ivermectin, which we completely understand, that it would be important for us to explain what we’re doing and where we’re going with this and what our portfolio of work is, in relation to something like Ivermectin”, she added when explaining the timing of the media briefing.
“We’re acutely aware [that] at the moment, we don’t have many options for prevention, for treatment of ambulant patients who are not too sick and to prevent them from getting sicker. And although we’ve got now some good evidence based options for hospitalised patients, everyone would like more. We totally appreciate that. And we also are very supportive of our health care providers who are on the front line, who are really desperate and looking for solutions. And it’s against that backdrop that the Ivermectin discussion needs to take place. So we’re very sensitive. We’ve had many conversations about this with expert committees, technical advisors and the board specifically on the on the issue of Ivermectin and how we should proceed with it.”
Doctor Semete added that the regulator hoped to clarify its role and the driving factors behind some of the decisions made around Ivermectin and its use in the treatment of Covid-19 patients.
“…We thought we could easily issue a press statement. But, because of the sensitivity of this matter, we thought, let’s have an engagement. I think it would be preferable for us to be engaging with the media, with the public, so that they understand the basis for some of the decisions that we make as a regulator. But also quite important… What we wanted to communicate is that we have listened and we have heard. We have been in a number of media interviews. We have engaged with the scientific community. We’ve had many discussions internally on this very pertinent matter.”
Dr Semete went on to explain that although the drug has been registered for use by the Food and Drug Administration, it has not been registered in South Africa for the specific use in treating people with Covid-19.
“So there was a comment that says this is a product that has been registered by the FDA for human use. That’s correct. But it’s not for the treatment or for prophylaxis, of Covid- 19, but it’s a registered product. What we have done since we communicated on the 6th of January, we’ve reviewed an extensive piece of data that has emerged. Firstly, we engaged with the World Health Organisation and there’s a statement that they have issued around this product. Again, they also indicate that there is currently limited data. They are working with Unitaid to review the currently ongoing clinical trials for them to be able to give sufficient data to provide us with a guideline on this matter. We must also indicate that we’ve engaged with other regulators that we work closely with, as SAHPRA, such as the FDA, the European Medicines Agency, the Medicines and Healthcare products Regulatory Authority in the UK. They have indicated a very similar position to us. We have also looked at recent data that was published as a follow on from the PowerPoint presentation that was made by Dr Andrew Hill. I want to highlight that it indicates that there is not yet sufficient scientific data that is robust enough to justify a regulator making a decision on this product and that the current studies that are ongoing need to continue and that more data needs to be generated from that. We attended the webinar that was hosted by Dr Hill on the 11th of January. The Ministerial Advisory Committee also released an advisory where they concluded again that there is insufficient data to recommend for the use of this product for the treatment or prophylaxis.”
Dr. Semete went on to explain SAHRPA’s approach to the controlled use of Ivermectin in humans and why the regulator decided to implement a Compassionate Access programme for the controversial treatment.
“The approach that we will be taking going forward is that we will facilitate a controlled compassionate access program for Ivermectin. This does not mean that our position changes around the availability or the lack of availability of scientific data, but we had to, as a regulator, have very in-depth discussions around the context which we find ourselves in with the pandemic, with limited options being available. It’s on that basis that we are saying we will facilitate a controlled access program that will enable us to monitor the use of this and to get the health care professionals reporting to us.”
In conclusion, SAHRPA’s CEO defined the role of the scientific community and medical practitioners in reporting data on efficacy, safety and side effects in patients permitted to use Ivermectin.
“The framework that we will be putting in place will be an evolving framework. We had an engagement yesterday with the scientific community, with some of the medical practitioners. We also had the GPs associate represented through the association. And we listened to what they had to say. We will again be looking at a longer term access protocol while we await for scientific data within this group of scientists that we engaged with. Universities will very soon be submitting their clinical trial applications so that we also then as a country generate our own data. We are saying we have heard you. We’re putting in place a compassionate access program that will be controlled. We’ve considered the risk benefit of having this product available. We will have to work very closely with the medical practitioners because they will be very important in the reporting of any safety effects, any adverse side effects, but also of reporting on any positive benefits of this.”
Members of the media asked Prof. Reese and Dr Semete questions relating to Ivermectin and the approval of Covid-19 vaccines in the country.
With the rollout of the AstraZeneca vaccine due to start next week, what do you say to those who still do not want the vaccine? And are there any other applications in the pipeline?
Prof. Rees: AstraZeneca vaccine, we will outline the processes that we go through. But this has been granted emergency use and there’ll be a press conference later with the minister of health on on this. But what do we do about those who don’t want it? And I think this is a real concern because vaccines are certainly going to be just about our most powerful tool to break the grip of this pandemic. And we are going to have to at the moment and we heard the president say yesterday and complain about the lack of access of low income countries to purchasing vaccines. That is incredibly important because we are going to have to at the moment get which vaccines are available to us and we need to use them to protect, in the first instance, the health care workers. There are other vaccines that are that have been applied for, and that includes Pfizer. The J&J Vaccines and other vaccine developers have also been in conversation with SAHPRA about putting in an application. This is actually exciting and it’s good. But what do we do about those who don’t want it? I think that we’ve just got to really, really discuss this and push and push and push. On a call of some of the countries, the scientists this morning, without exception, everyone is saying that we all want these vaccines. We would all take these vaccines and we want them rolled out as quickly as possible because that rollout is not only going to stop deaths, but it’s also going to stop the emergence of variants if we can get sufficient coverage. So it’s incredibly important. So I think we have to build confidence in vaccines and we have to build confidence and Covid- 19 vaccines in particular, and the fact that although they have been developed very rapidly, that they are effective. We know how effective they are in clinical trials. We know their safety profile and clinical trials. And of great importance is that we will be monitoring safety and effectiveness once they are rolled out into the community. We need to get spokespeople, other than scientists and regulators. We need to get young people that are willing to take it. We need to get celebrities. And we’ve obviously got a president and a health minister who are backing this. But we do need to get many more spokespeople to really push the importance of of being vaccinated.
Has any medical practitioner attempted to use of ivermectin on a Covid- 19 patient despite the ongoing court case?
Dr Semete: Are we aware of any GPS that have attempted to use this product? We have anecdotal evidence, but obviously because this is an unregistered product, it’s not easy for us to track all of that. But we’ve got anecdotal evidence of the use thereof. As we’ve indicated, we see widespread use and we’re seeing an emerging black market. And we hope that this compassionate use, controlled access will at least enable us to ensure that this product is used adequately and that we can get reporting on this product. A number of drugs have been repurposed… It’s very much around a specific indication. So you’ve seen around Covid- 19 with Hydroxy Chloroquine and Chloroquine. Those are drugs that would be repurposed, purpose of clinical trials that went on and you saw written about. So we are very much not throwing away anything, but we’re are for a specific indication, for specific doses, et cetera. There needs to be further studies that are conducted.
Why ban a thirty year history and plenty of studies [of Ivermectin] for human use?
Prof. Reese:[In terms of Ivermectin] This is registered in South Africa for veterinary use, it’s widely used globally for veterinary use. It hasn’t been registered for human use because some of the [most] common conditions that it’s used for just don’t occur commonly here. These are what we call neglected tropical diseases. We have given permission for importation for things, as you mentioned, head lice, scabies on occasions for named patients, which is not being commonly done. When you get a registered drug, it’s because there’s a need in the country. If you have a very small need in the country, which is the case for Ivermectin, there is it’s very unlikely that you’re going to have somebody who would apply for registration of the product because it’s really not going to be a sufficient commercial interest in the way that we deal with that just to this Section 21. So it’s not that this has ever been banned, it’s just that it hasn’t been registered for human use.
We’ve only had Covid- 19 for a year… So we don’t have a 30 year history of anything for Covid- 19. So what we have done, though, and this is how ivermectin has come to the fore and more recently, Colchicine, which we had some potentially exciting data about. We’ve taken old medicines, we’ve taken existing medicines, and in fact, using artificial intelligence, these have been scanned to say which of these have the potential to be active against sars-cov-2. Then they’ll be taken into the laboratory and evaluated and many medicines have looked hopeful in the laboratory, including Chloroquine and Hydroxy Chloroquine, some of the antiretrovirals we use for HIV then sadly, when we’ve come into the clinical field, haven’t lived up to what we hoped. So we have been evaluating these repurposed drugs for just a year. So this [is] not, unfortunately, 30 years of evidence because we’re all running to try and find those medicines that are going to work against this disease.
Why is Ivermectin is not authorised for human use in South Africa, but it is in other countries?
Prof. Rees: I think just as a backdrop to those questions, I want to just stress something, because this is different to the registration of, say, the AstraZeneca vaccine, where we have unequivocal clinical evidence of efficacy. And we have from the clinical trials of about 24000 people, safety data. So what we have here is, is an older medicine, which has been around for a long time, but used for very different indications in its use. In those indications, we have safety data and we have efficacy data for those indications. So which is which is very good news because that gives us some background…. The current data that’s available to us in clinical trials is insufficient to give us convincing evidence of benefit in terms of efficacy, and that what we need is larger, better designed randomised trials that we would all hope we would all very much hope would give us a home run. But unfortunately, we also know that there have been occasions with those big and well done studies didn’t deliver on the earlier messages of the studies. So that is why people emphasise so much having these larger studies. The good news is for Ivermectin that there are studies already underway in a range of countries. These are larger studies and we would hope better design studies that are registered on an international clinical trials register. And that there are a number of first class scientists in South Africa who are also putting their hands up to urgently put forward protocols for studies, for different indications of use.
Explain in detail how compassionate access program for ivermectin will work? How would a doctor or a patient legally obtain the drug?
Dr Semete: In terms of the Compassionate Use Access Program. Let me start with that one. Well, as I’ve indicated, the issuing of very detailed guidelines around this, if we were to discuss it, and I think it will take the bulk of the remaining part of the meeting, that we will provide that detail again within that compassionate access. Those of you who have, you know, the medical practitioners that have used Section 21 before will be familiar because that’s that will be the principles that you’ll be building into this compassionate use access program. This is a program that will be open to all patients. So it’s not only for a certain cohort. To the point around world health care, you know, will they be priority recipients? Definitely not. We will then review the application as it comes through. Indeed, for the compassionate use program [it] will need to be the health care professional. And this is how our Section 21 program works because they will then be taking accountability and responsibility for the safety monitoring of this product, also for monitoring the impact that is having on the patient from an efficacy perspective. So there’s a large onus that we’re putting on the health care professionals to monitor the progression of the patients.
Can SAHPRA please give an update on the AstraZeneca vaccine on its way from the serum institute? Is it true that SAHPRA is currently reviewing the relevant vaccine data with a view to granting it approval for its emergency use in the country?
Dr Semete: I’ll talk around the process that we follow when evaluating a vaccine or any other medicine. So typically what happens is that we would then receive an application from the applicant who would be the manufacturer, for example, in this case. And we’ve got a very detailed template that they need to plan to compete. That includes aspects of quality, that includes aspects of clinical safety we’re in and also clinical efficacy. We also, quite importantly from a quality perspective look at what we would call good manufacturing practices. So our team would be going off to the facilities and seeing that these facilities comply with good manufacturing practices. We also look at aspects of what we call names and scheduling. So there’s a whole detailed application form that each applicant needs to put in place. And we will then review that in detail. So with the market authorisation, we would receive the full dossier and we would then review it in its totality. We do have mechanisms with other regulators where we can apply reliance and with that we can rely on the decisions of the WHO… It would be under the WHO pre qualification program. So there are all those mechanisms. What we would then do is go through every single aspect of this dossier that is submitted and in every single instance, we need all this information provided. Now, the difference between Section 21 and full market authorisation is the following… With the Section 21 is an instrument that’s made available for emergency use, access of a product that is unregistered. So this is a mechanism that we’ve used and it’s in our act for many, many products, even for Ivermectin itself… And in this case, this is a mechanism that was used for the Serum Institute, AstraZeneca vaccine. And the applicant there was the Department of Health and actually around the question of whether this has been authorised. So there was a public statement that was published by the Department of Health on Friday…We’ll be having a discussion on vaccine where we’ve indicated that the Section 21 authorisation has been granted.
Can SAHPRA please provide an update on the J&J application? When does SAHPRA expect them to get authorisation? And what is outstanding, for example, clinical data, dossier submission or the triple one clinical trial outcomes? Please also clarify if the authorisation being considered is conditional and what does and what those conditions are and why distinct from Section 21. Please give us an update on the pipeline of all vaccine registrations, applications expected. For example, name individual , firms not mentioned Pfizer and how far in process the all are.
Dr Semete: We will be taking the public through what steps we followed, what did we review, what were the considerations… It was quite a detailed review in our pipeline. We also have the J&J application. As we’ve indicated, we are applying what we call a rolling review. So as you’re aware, a number of these vaccines are still under evaluation. These ones in particular, they are at very advanced stages of their phase three studies where we’ve got the initial data that indicates their safety and efficacy. So we’re conducting what we call a rolling review for these. This is a mechanism that we’ve agreed to as a global community of regulators to say we will not wait for the full information to be available, let the information in as it’s generated and we will evaluate. So we’re still at that point with J&J and there’s additional information that is still required. Unfortunately, I can’t go into the details of the actual applications or the one that we’re busy with. The review thereof is the final vaccine. So those are the two that we are currently busy with. And we’ve issued a Section 21 authorisation for the Serum Institute product.
Is it correct that SAHPRA will not consider any vaccine if companies do not agree to share their clinical data with the regulator? And is this the case with Moderna? Therefore, by extension, Moderna vaccine is not being considered for South African use currently. What about the Russian and Chinese vaccines and potential clinical data holes? Are their vaccines being considered by SAHPRA or not?
Dr Semete: The question around the Moderna. The regulator would need to ensure that whatever product that is authorised complies with the requirements for safety, efficacy and quality, and in no way would authorise a product where none of this information is available. So it’s quite important that all this becomes available. It depends on whether we received an application or not. So in the case of Moderna, we have not received an application as the regulator in the country. As soon as they submit that to us we will review that application. An aspect that we’ve included in our processes for review of vaccines is what we call a pre submission meeting that we have with all the applicants, wherein they take us through some of their preliminary data to indicate what it is that you require for them to make available, as part of our regulatory package that they need to complete. We’ve had these discussions with the ones that have submitted. We’ve had discussions with Sinopharm from the Chinese vaccine, we’ve also had the Russians reach out to us and we’ve had discussions. So we’ve been very open to having discussions with many applicants. It’s not only limited to these, it’s a number of applicants that we’ve been engaging with and providing guidance on this.
Listen to Professor Reese on the need for local data generation:
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