28 April 2020

COVID-19 Dissecting the Therapeutic and Vaccine Landscape

Anti-virals? Antibodies? Immunomodulators? Vaccines? If you have a functioning pair of eyes and ears, you will have more than likely heard some of the following verbiage in the media or directly from the US President himself – ‘hydroxychloroquine’, ‘Remdesivir’, ‘Tamiflu’ or possibly the more obscure arthritis drugs ‘Actemra’ or ‘Kevzara’.

There are several drugs which have been touted as possible curative therapies to treating COVID-19 – but how impactful are these therapies expected to be? When will we know whether they are effective or not? Are they just a means to an end before a vaccine is eventually found?

Repurposing Current Therapies – an Increasingly Competitive Landscape

There is generally positive sentiment around potential COVID-19 cures coming in the form of treatments that are already available in other disease areas. While regulators have not yet approved treatments per se, there are a number of treatments now receiving approval for compassionate (emergency) use, for example anti-HIV drug Kaletra and anti-malarial Chloroquine. In the EU, France and Italy joined the US in authorizing emergency use of Chlroroquine and hydroxychloroquine, making the drugs available to more COVID-19 patients.

In the near term, clinical data is expected from in-human trials of Gilead’s MERS/Ebola drug, Remdesivir, as well as legacy anti-inflammatory, Chloroquine, both of which are expected to come in late April. Encouraging Remdesivir compassionate use data demonstrated clinical improvement and no new safety signals in severely ill COVID-19 patients. However, it recently came to light that Remdesivir failed its first randomised clinical trial in 237 patients, which was “accidentally published” by the WHO. The Chinese trial showed that the drug did not improve patients’ condition or reduce the pathogen’s presence in the bloodstream. However, Gilead have since responded by playing down the outcome suggesting the Chinese trial was underpowered to enable conclusions as it was terminated early due to low enrolment. The company, who is conducting its own studies of the drug, expects to announce data from a trial in severe COVID-19 patients at the end of April. Should these results prove to be positive in a larger population (potentially ~6000 participants), the implication is that it could lead to lowering overall mortality rates but will depend on access and availability. Gilead has already requested that the FDA rescind Remdesivir’s newly requested orphan drug status following backlash. This would allow the company to supply the drug at a much cheaper price than its current price tag of upwards of $100 per dose (once daily 100 mg dosing, following an initial 200 mg intravenous loading dose), with the aim of making the drug more accessible upon approval.

Another pharma big hitter, Novartis, has also recently entered the fray having obtained the FDA’s go ahead to proceed with a company-sponsored Phase 3 clinical trial of anti-malarial hydroxychloroquine in ~440 hospitalized COVID-19 patients. Evidence supporting this generic drug, touted as a “game-changer” by Donald Trump, so far has been limited, so Novartis and its generic partner Sandoz, are hoping to generate robust data to bring this drug into the COVID-19 fold. The company has already announced its intention to donate up to 130 million doses of the drug globally to fight the pandemic and admits it has little to gain financially from conducting the large Phase 3 clinical trial, which will begin enrollment in the next few weeks.

For more moderate forms of COVID-19, in addition to potential Remdesivir results in May, flu anti-viral Avigan is also touted as a potentially effective option. Japanese developer Fujifilm, famous for film and camera products as well as now healthcare products, has ramped up development of this agent and boosting its supply chain capabilities to have 100,000 treatment courses readily available by July. Phase 3 clinical trial results are anticipated in the May-June timeframe.

Promising DNA/RNA Vaccine Approaches

Despite early promise of repurposed drugs as potential COVID-19 cures, vaccine-makers are still coming through in swathes, with DNA/RNA-based approaches leading the pack. Moderna and Inovio are two of the key players both in the clinic and hoping that when immune data begins to emerge this will provide clarity on the type of immune response to be most effective for a COVID-19 vaccine. However, the timelines for potential vaccines are further out with Phase 1 data not due until mid-late 2020 timeframe. It’s worth mentioning that vaccine experts like Inovio are well positioned for rapid turnaround of a candidate as the company has vast experiencing in developing vaccines for other viruses such as MERS-CoV, Ebola and Zika. Another key advantage and string to Inovio’s bow is that its candidate INO-4800 is stable at room temperature and could therefore be quickly manufactured in large quantities – a significant differentiator to other vaccine candidates.

Uncertainty is Certain for a Bit Longer…

Despite positive sentiment about these developments there is still a lot of uncertainty and many unanswered questions – what will the Phase 3 data for the existing therapeutics end up looking like and how will they compare? Will companies be able to ramp up supply chains to accommodate pandemic-levels of cases? What do we know about the COVID-19 virus itself? Is it mutating and able to evade a vaccine? Of course, at this time it is still unclear and the landscape is ever-changing. This is also a very brief glimpse into a few of many potential therapeutic and vaccine options that could prove to be impactful in improving COVID-19 clinical outcomes and have broader societal/economic impact.

There are however a few certainties looking ahead: healthcare companies will continue to get involved with the COVID-19 landscape and many will continue to question their integrity around pricing. A recent UK-based study showed that many existing drugs with the potential to fight coronavirus could be produced and sold at a profit for as little as $1 a day or less. Pharma companies such as Gilead scoffed at the findings saying they do not accurately reflect the true cost of manufacturing. But it just goes to show the pressure these developers are under to make drugs accessible in light of a global pandemic.