Rapid spread of the novel coronavirus, SARS-CoV-2, presents an enormous challenge for the global community. Containing the virus, and treating the resulting disease, COVID-19, has become top priority for governments and health organisations around the world.
How have science and industry responded? Several months into the outbreak with seemingly hundreds of news stories appearing every day, and as a follow-up to our previous article, here we distil some of the most promising clinical candidates. Casting an eye to the future, we consider how the areas that hold the most potential for success will shape the intellectual property landscape for years to come.
Vaccines: one path out of the pandemic
An effective vaccine that provides long-lasting protection against new infections and halts the spread of COVID-19 is undoubtedly the ultimate goal.
At the start of March 2020, the World Health Organisation (WHO) listed a total of 35 candidate vaccines in preclinical evaluation for use in COVID-19. That number now stands at 94, with at least 8 more candidates having advanced to clinical trials.
First to begin clinical trials of a COVID-19 vaccine was Moderna, with their vaccine “mRNA-1273”. The vaccine contains mRNA encoding the coronavirus spike protein which, when introduced to the subject, induces the body’s own cells to produce viral antigens and initiate the immune response. If successful, Moderna’s mRNA vaccine could be the first-ever mRNA vaccine to receive approval for use in disease, and could provide a roadmap for other developers using this technology.
Also among the group of candidates already in clinical trials is “INO-4800”, developed by Inovio Pharmaceuticals. Using their proprietary DNA medicines platform technology, Inovio designed their vaccine in just three hours following publication of the novel coronavirus genetic sequence. In China, other frontrunners have been developed by CanSino and Sinovac, whilst in the UK, human studies are underway for Oxford University’s ChAdOx-1 vaccine.
If a safe and efficacious vaccine is found, how will this be produced on a global scale? DNA and RNA-based vaccines have never been tested against a backdrop of such widespread international demand. Beyond vaccine development, further challenges of manufacture, scalability and preservation in countries with little access to refrigeration emerge. We expect to see pioneering new technologies rise to meet these challenges.
New applications for old drugs
For a new drug, the road to clinical approval is a long one. Although government-sanctioned emergency measures may accelerate availability for those most at risk, it is likely to be 12 to 18 months before a vaccine is commercially available.
In the nearer term, repurposing of existing drugs for treating COVID-19 remains the most promising option.
Remdesivir, an antiviral drug from Gilead, was originally developed for treatment of Ebola virus but had not previously received approval for use in any application. Preliminary data from a Phase III clinical trial now shows remdesivir shortened the time to recovery for COVID-19 patients by approximately four days, compared to those not receiving the drug. Remdesivir has now received emergency authorisation from the FDA for use in severely ill patients with COVID-19, and seems the most promising treatment lead so far.
Remdesivir is one of four treatment options currently being trialled by over 100 countries, as part of the WHO’s “Solidarity” clinical trial. Also part of this global mega-trial are the antimalarial drugs chloroquine and hydroxychloroquine. While much has been made of these drugs in the media, there is as yet insufficient data to show they are effective. Both drugs appear to be associated with serious cardiac arrhythmias, and it remains to be seen whether they will prove safe in seriously ill patients.
Another arm of the Solidarity trial will test the anti-viral combination of lopinavir/ritonavir, approved in the US for treatment of HIV. Some patients will also receive the anti-inflammatory agent interferon β1a in combination with the anti-virals. Ideally, such a combination would both kill the virus and alleviate symptoms of COVID-19. Is there a magic bullet that could encompass both activities with one drug? That is the thinking behind Nearmedic International’s novel synthetic peptide, which has both antiviral and immunostimulatory activity and is currently undergoing preclinical testing.
Using known compounds can still lead to new discoveries. Each success or failure of a known therapy teaches us incrementally more about the virus, and elucidates new disease mechanisms that can be used for invention creation in years to come. As previous coronavirus outbreaks such as SARS and MERS have fizzled out, so too has funding and interest. Given the scale of the current crisis, it is likely to be a different story this time.
The fast route: antibodies and plasma
Although repurposing an existing drug is faster than creating a new one, perhaps the quickest and most immediately available treatment option is to use plasma obtained from those who have contracted COVID-19 and recovered. The approach has been successful in reducing mortality in Ebola and MERS, and preliminary studies in COVID-19 have shown promising effects in severely ill patients.
The use of convalescent plasma to counter viral infection is based on the assumption that plasma contains antibodies against the virus, which suppress viral replication in the body. One drawback of this therapy is the potentially high variation in the quantity of antibodies found in plasma collected from different individuals. Typically, the higher the antibody concentration, the more effective the treatment. Antibody specialist, SAB Biotherapeutics, may have found a way to overcome this issue with their DiversitAb platform, which uses genetic engineering to obtain fully human polyclonal antibodies from cows. By generating large amounts of plasma and with antibody concentrations reportedly far higher than that obtained in convalescent plasma, this technology has potential for rapid scaling up, whilst avoiding the delays associated with screening human plasma donors. SAB’s human polyclonal antibody for COVID-19, SAB-185, is expected to begin clinical testing in early summer 2020.
Innovation in diagnostics
Effective containment of any infectious disease requires rapid and accurate diagnosis of infected patients.
Researchers at the Broad Institute and the McGovern Institute have harnessed the power of CRISPR technology to provide a new diagnostic tool in the form of a simple paper strip test. The test uses the CRISPR/Cas13 construct which selectively cleaves viral RNA. Similar to a pregnancy test, a line appears on the paper strip if the virus is present. Sherlock Biosciences Inc. are expected to develop this test commercially, with Mammoth Biosciences also developing a CRISPR/Cas12 based test using their “DETECTR” platform, which reportedly takes as little as 40 minutes from sample to result.
Antibody-based diagnostics, which provide the advantage of diagnosing those who have had COVID-19 in the past but are no longer infected, are also now being produced at impressive pace. Particularly promising among these is Roche’s Elecsys® immunoassay, demonstrating excellent specificity and sensitivity. Bio-Rad, Cellex and Abbot have also all received FDA emergency use authorisation for their antibody test kits.
Highly efficacious antibody tests could pave the way for so-called “immunity passports”, potentially allowing an individual to return to work following a positive COVID-19 diagnosis. Tech firms, such as UK based Onfido, have the capability to connect an individual’s facial biometric data with their diagnosis, creating a powerful and highly secure digital certificate. Currently, questions remain about long-term immunity to COVID-19 following infection. Judging by the rapidity with which the scientific community has acted so far, we anticipate answers to these questions will come swiftly.
Urgent unmet needs remain for viable treatment options for COVID-19, and in the longer-term, for its prevention. Clinical studies continue apace and we are encouraged by global collaboration and promising early data. Accurately diagnosing COVID-19 infections, both current and past, is a critical facet of many national government’s strategies to safely ease social distancing measures. With increasingly accurate tests coming through the pipeline to commercial availability, we are hopeful these tests will help societies advance out of 'lockdown' and edge closer to normality.
Working in intellectual property, we are privileged to see first-hand the speed and innovation with which the pharmaceutical industry and scientific community have responded to this global emergency. We are excited to see what further inventions this enormous investment of resources and attention yields in the future.
If you have any questions, please contact our Life Science and Chemistry team members Tom Leonard or Jessica Duncombe, or your usual Kilburn & Strode advisor.