Balancing regulation and innovation in the race for a coronavirus cure

23 April 2020

In the Pharmaceutical industry, both innovation and regulation are vital; whilst innovation results in the development of new or improved treatments, regulation ensures medicines developed are safe for human consumption. These two elements of drug research and development go hand in hand, however, with the drug approval process averagely taking 12 years from early innovation stages to approval, what happens when a sudden outbreak occurs which requires a solution – and fast?

Currently, we are facing the COVID-19 pandemic. This is testing the world’s ability to develop tests and treatments for the virus, as well as challenging bodies such as the FDA and MHRA to approve such treatments efficiently. Already, the FDA has been criticised for delays in approving testing kits, with suggestions that prevention efforts were hindered as a result. On the other hand, others are concerned that the processes for evaluating drugs may go away during a public health crisis, which could lead to consumption of unsafe drugs; after all, regulations are stringent for a reason. This is not the first time the balance between a duty to treat patients and the need to learn as much as possible about the treatment has occurred.

Ebola’s “Magic Serum”

The Ebola epidemic in the summer of 2014 quickly spiralled out of control in West Africa. There was enormous pressure on health services, with no proven safe therapeutic treatments or vaccines available. To paint a picture of how serious this was, the fatality rate was 57-59% in hospitals where the most unwell patients were, and around 40% fatality rate overall.With this in mind, the international community began to consider the use of experimental products to treat patients.

Initially, the World Health Organisation (WHO) were opposed to the use of untested products due to understandable mistrust. However, when two American aid workers became critically ill with the infection and fully recovered following treatment with ZMapp – an experimental type of biologically engineered, genetically modified tobacco plant - public perceptions were changed. The product had previously been proven effective on Rhesus Macaques monkeys, with a 100% success rate if administered in the first five days of treatment; however, the drug had not been tested on humans. Naturally, this caught media attention worldwide, ZMapp being declared as a miracle cure. Despite this, it is important to note that it was unknown what effect the product had on the patients due to it being untested; without such evidence, it was unclear if the drug helped, hindered or made any difference at all on the recovery.Some cynics suggested it was instead the superior care international workers received, backed up by the statistic that 22 of 27 patients evacuated to Europe or America during the pandemic survived due to state-of-the-art care.

Either way, whether ZMapp was a miracle drug or not, it caused more controversy than simply the debate of its effectiveness. Upon hearing Americans were being treated with this “magic serum”, African health authorities questioned why the two Americans had access to a cure, when they had been told no such treatment exists for the thousands of Africans suffering. Additionally, there was a debate about the wider use of experimental treatments in general – should as many patients as possible be treated due to the high mortality rate, or should clinical trials be carried out quickly, so more was understood about the drug? Though ZMapp appeared to have no side effects for the Americans, without randomised trials and decisions based on more than just two successful cases, it could not be deemed safe for all. On the other hand, is it ethical to research at all, with people dying due to lack of treatments, pressure on frontline staff and continued spreading of the epidemic? The WHO declared that it was, to be sure of positive patient outcomes and ensure resources were used efficiently.

Expanded Access Exemption

Despite this, it is still possible to receive experimental therapies outside of a clinical trial. If we use the FDA as an example, under section 564 of the FD&C Act, an Emergency Use Authorisation (EUA) can be used against biological threats, whereby the FDA can authorise the use of unapproved new products, or uses of existing products, if the Secretary of the US Department of Health declares an emergency threat. This was declared on March 24th for COVID-19.

The FDA approval process for any potential treatment would be made through an Investigational New Drug application (IND), for an expanded access exemption (also known as compassionate use). Typically, for the application to be approved, the patient must have an immediately life-threatening illness with no alternative therapy, the benefits of said treatment must outweigh risks and the drug development program must not be compromised. The rules around this are strict for all regulatory bodies, and it is not frequently used on large populations due to the risk factor and as it can be seen as a threat to drug evaluation processes, which requires vast amounts of evidence.

The FDA had previously approved a widespread expanded access exemption during the Swine Flu outbreak in 2009-2010. Peramivir was used for between 1,200-1,500 severely ill patients, though eventually, a randomised trial failed to show any benefit of the drug for the Swine Flu compared to a placebo; it was however subsequently approved for uncomplicated influenza only.

Where does this leave COVID-19?

For the coronavirus, drugs such as Remdesivir – an investigative antiviral drug – have already been granted expanded access. Over a thousand patients outside of clinical trials to date have taken this drug - a number which is only likely to increase over the coming months. In addition, on an FDA press release on 24th March 2020, researchers were encouraged to submit requests for the investigational use of convalescent plasma – where the antibody-rich liquid part of blood donated by those recovered from the virus is administered to patients for whom there is no alternative treatment. Individual patients with serious infections can seek expanded access to this if their doctor applies for a single-patient emergency IND.

As a result of expanded access and approval of investigative drugs, the most vulnerable patients should not be denied the innovative new potential treatment, providing some balance between regulation and innovation. However, this depends on if the applications are actually approved and there still has to be some consideration of potential unwanted side effects. Additionally, many still consider the process as taking too long, the media speculating it could take over a year for a cure to be developed and approved.