COVID-19 presented a novel infectious illness that has caused significant worldwide morbidity and mortality with significant economic and cultural effects. At the same time researchers worked quickly to study the virus that causes COVID and develop effective treatments. Within a year multiple vaccines were approved and in production, giving us a powerful tool to reduce the pandemic. It took longer to develop effective anti-viral treatments for active infection (after some false starts with drugs like hydroxychloroquine and ivermectin that turned out to be ineffective).

However, recently two anti-viral drugs have been approved that have been shown to be highly effective in treating early COVID illness. Molnupiravir (by Merck) is an oral drug that has been shown to reduce the chance of hospitalization and death by 50%, if taken early for mild COVID. Benefits are less if taken later in the course of the illness, and more research is needed to see if it is effective in moderate to severe COVID. The most recent analysis of this data, however, show only a 30% in risk of hospitalization. An independent study is also underway, and regulators are waiting to see if even this 30% reduction holds up.

Nirmatrelvir (by Pfizer), meanwhile, was found to reduce the chance of progressing from mild COVID to severe COVID by 89% compared to placebo. This drug is given in combination with ritonavir as a “pharmacokinetic enhancer” to block metabolism and prolong the effectiveness of nirmatrelvir.

The addition of these drugs (especially nirmatrelvir) to existing treatment, and vaccines for prevention, will help turn COVID into a more manageable disease and also help the transition to living with endemic COVID, much like we live with endemic flu. One of the greatest burdens of COVID is the dramatically increased hospital admissions, especially during spikes, that overwhelm staff and resources and push aside more routine care, resulting in negative health outcomes. Reducing hospitalizations among those who get COVID is therefore highly useful.

The World Health Organization (WHO) has added molnupiravir to their list of recommended COVID treatments, and state:

molnupiravir should be provided only to non-severe COVID-19 patients with the highest risk of hospitalization. These are typically people who have not received a COVID-19 vaccination, older people, people with immunodeficiencies and people living with chronic diseases.

There are two reasons for limiting the use of these antivirals. The first is that, while they appear to be safe with few side effects in the clinical trials so far, they are new drugs. When we start giving them to millions of patients it is possible, even probable, that new side effects will emerge. On a risk-vs-benefit basis, therefore, they should be limited to the people who most need them.

The second reason is that the availability of these antivirals is limited. Production can only be ramped up so quickly. At first supplies were limited even in the countries where production was located, but there is now enough availability that they are available for any who need them. That is – in developed Western nations. Supplies are still critically limited in poorer countries.

Unfortunately, as has now been documented in a recent BMJ article, this has lead to the creation of a black marker in generic versions of these drugs. Their reporters contacted an online market, Indiamart, and report:

Within hours, three sellers got in touch to make offers, even though the Mexican authorities have not permitted generic versions of the drug to be imported into the country. One seller gave advice on how avoid customs.

Black markets for generic versions of these drugs sprang up almost instantly when the initial studies created hype about their effectiveness. As the BMJ article points out, this is problematic on many levels. First, online black markets do not require a prescription (of course) or the involvement of a physician. Like all drugs, these antivirals may not be safe for some populations (such as women who may be pregnant), and can have drug-drug interactions. They should only be taken under physician supervision, or as part of a clinical trial.

There is also a huge concern about indiscriminate use of these antivirals, which can cause antiviral resistance (just like indiscriminate use of antibiotics can cause antibiotic resistance). Those who do not truly need the drug will incur costs and risks without probable benefit, and can eventually reduce the effectiveness of these drugs for those who do.

Further, there is no quality control for black market drugs, and every reason to think that the sellers involved are less than scrupulous. This opens the door to many risks, such as taking worthless substances, unknown substances which can cause allergy or negative interactions, and risking contamination and adulteration.

The BMJ authors correctly point out that this is a high risk whenever there is dramatically unequal distribution of healthcare resources. However, the risk goes beyond that. Even the perception of scarcity will drive the black market, and that perception can be entirely manufactured for the purpose. A drug can be “scarce” because it is not approved, because it is not safe and effective. The lack of approval can then be blamed on a conspiracy, with the black market as a remedy.

The BMJ study also highlights the fact that the availability of online marketplaces can quickly establish a black market infrastructure for new products. Also, online markets can exist in locations with lax regulations but supply anywhere in the world. Local regulations may therefore be of little benefit, especially if those same black marketers are adept at avoiding customs.

One solution to the exploitation of black market drugs (which tends to target the most vulnerable) is tighter regulations, and more international regulations. However, this addresses only supply. We need to also address demand. In cases of drugs and products that are inherently fraudulent or useless, education is the best tool. But when it comes to generic knock-offs of effective drugs, improving the supply, especially to poor nations, can also be effective. Merck has announced, for example, that they will offer voluntary licenses to generic manufacturers in poor countries, and moves like this can be a big help.

Author

  • Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.