– Nafis H.
The novel coronavirus pandemic has governments scrambling to declare national emergencies and orders to “shelter-in-place” for residents of major cities. Scientists, both in the public and private sector, are working around the clock to develop a vaccine for this virus, but best case estimates suggest that it is still going to take 18 months for the vaccine to enter the market in quantities that are needed to immunize a majority of the population. At the same time, there is also a race to develop effective treatments for this disease – whether through novel drug discovery using machine learning and synthetic biology, or testing existing antivirals and repurposing other drugs in clinical trials. Most of these efforts in the US are being carried out by the private sector with financial help from the federal government, and stories are already emerging regarding battles over intellectual property (IP) and price-gouging. Given past history and continuing practice of price gouging by the pharmaceutical industry, there is a strong chance that even if the federal government subsidizes the cost of any approved antiviral, such as remdesivir owned by Gilead Biosciences, low-income patients will be unable to afford this medication in the long term. This is manifested in the facts that the Health Secretary Alex Azar recently said that he couldn’t guarantee treatments or vaccines would be affordable for all Americans, the presumptive Democratic nominee Joe Biden refused to embrace the march-in rights which would have made the vaccine/treatment affordable, and that despite Democrats’ push for stronger provisions to make the vaccine/treatment affordable, the pharma lobby was able to get those removed from the coronavirus relief bill. A recent report from epidemiologists at Imperial College, London, suggests that while the pandemic is being treated as an emergency at the moment, the virus itself is not going to go away in a couple of months and will continue to infect populations over the next year or when a vaccine becomes available. This is why it is imperative that low-cost treatment options that are cheap, safe and have existing generics be made affordable and accessible to all by the US government and the World Health Organization (WHO).
This is where the anti-malarial drug chloroquine and its analog hydroxychloroquine can come into play. It has already been used by Chinese and South Korean clinicians and is included in the Chinese treatment guidelines for elderly patients (who have higher mortality risk with this infection). A French clinical trial found that a daily oral dose of 600 mg of chloroquine was also able to effectively reduce recovery time for 75% of coronavirus infected patients. The Dutch Center for Disease Control (CDC) suggests including chloroquine as a treatment option for severe covid19 infections with 600 mg followed by 300 mg after 12 hr on day 1, with 300 mg twice/day for days 2-5. They recommend no more than 5 days of continued treatment based on possible side effects. Similarly, the Chinese and French guidelines also suggest that chloroquine treatment should be limited to 7-10 days. More recently, a US clinical trial has started to test the prophylactic efficacy of chloroquine post covid19 exposure. A meta-analysis found that there are 23 ongoing clinical trials in China on the efficacy of chloroquine and hydroxychloroquine, and that chloroquine has enough preclinical evidence to be moved forward to controlled large randomized clinical trials. Chloroquine’s antiviral activity is believed to be based on it raising the endosomal pH in the cells, thus inhibiting viral entry into the cell and release from the cells, key steps required for increasing viral burden in the patient.
Another possible cheap and safe option that already exists in the market is the anti-helminthic drug Niclosamide. Niclosamide has already been shown to inhibit other positive sense single-stranded RNA viruses such as Zika and SARS-CoV (responsible for the SARS outbreak in China in 2002-2003) in laboratory experiments; its antiviral mechanism is similar to that of chloroquine and hydroxychloroquine. Additionally, Niclosamide has been shown to be well tolerated in cancer patients, who fall into the immunocompromised category, and has almost no contraindications and therefore, may be a better choice than chloroquine which has contraindications with anti-arrythmic and anti-psychotic drugs.
While the preclinical data is encouraging, and the clinical reports are promising, it goes without saying that these drugs should be used only after properly tested in large randomized clinical trials. However, these drugs have already shown clinical safety, are off-patent and therefore can be manufactured widely by any company, and have existing generics that are cheaper. For example, generic chloroquine phosphate costs $74 for 30 tablets (500 mg) on the drug website GoodRx,compared to its average retail price of $494; Niclosamide costs just $0.24 per oral course of clinical treatment of tapeworms. Additionally, these drugs are widely available – in central America, chloroquine can be obtained over the counter; both of these drugs are listed on the World Health Organization’s list of essential medicines. The 21st Century Cures Act, passed in 2016, allows the Food and Drug Administration (FDA) to accelerate approval of existing drugs proven safe for other indications. Given these circumstances, the WHO and US government should therefore prioritize niclosamide and chloroquine/hydroxychloroquine, over antivirals that are not showing as much promise, for large clinical trial settings and rapid deployment. Chloroquine manufacturers are already thinking along the same lines, but unless the government and international agencies intervene, we are going to be seeing more instances of price-gouging of these drugs as well.
The ugly politicization of coronavirus treatments is already beginning to manifest: there has been (largely unverified) report of President Trump trying to poach German scientists to develop a treatment for distribution exclusively in the US, Gilead Biosciences and Chinese firms are engaged in a battle over intellectual property rights, the US government is refusing to allow Cuba to supply interferon alpha 2B as a treatment for coronavirus, drug companies anticipate making a killing on life-saving antivirals once approved, Wall Street is pressuring healthcare companies to raise prices of drugs and medical devices, and confusions and contradictions between President Trump and the FDA Commissioner over approval of chloroquine for covid19 treatment – none of these circumstances bode well for low-income communities in the US (given the sorry state of the existing healthcare system) and low-income countries who will see a surge in coronavirus infections in the coming months. Lost in the political weaponization of any effective treatment will be evidence-based medicine and any opportunity to dissolve the existing inequities in healthcare access in the US and globally.
A pandemic implies a global spread – the coronavirus infects regardless of class, race, ethnicity, sex and borders; however, the structural inequalities embedded in our society prevents equal access to diagnosis and treatment. With the socioeconomic and political order in turmoil, this is the moment when we need a coordinated response to stop this viral disease, one that can be made available for all and not only to a few; we must fight back against any instances of coronavirus capitalism. The WHO and the governments should be prioritizing putting cheap, safe and low-cost options, such as Niclosamide and Chloroquine in randomized clinical trials rather than the antivirals whose IP will belong to the private sector which has a history of denying life-saving medication access to those most in need.
Author’s Note: The idea and data behind using Niclosamide as a possible treatment for coronavirus was proposed by Dana Cairns, PhD, a Postdoctoral scholar at Tufts University.