Patents, Ivermectin, and COVID-19
I recently had an email discussion with David R. Henderson, Research Fellow, Hoover Institution, and Michael F. Cannon, Director of Health Policy Studies, Cato Institute. The topic was drug patents. Should they exist? Is 20 years the right duration?
I was arguing that one problem with “short” drug patents was that companies stop investing in finding new uses (i.e., new diseases, or what are called indications in this industry) for a drug once the patent expires or is close to expiring. Why would you remodel your kitchen if a year later you would lose all ownership rights to your house? That would be foolish. You would never see a return on your investment.
Then I wondered if there were cases where longer patent lives would have had significant effects on major health events. The case I will explore here involves Merck & Co., ivermectin, and COVID-19.
How would the COVID-19 pandemic have played out if Merck’s patent on ivermectin had been in effect longer?
First, some background.
Ivermectin was developed and marketed by Merck & Co. while I worked there years ago. Dr. William C. Campbell and Professor Satoshi Omura were recipients of the 2015 Nobel Prize for Physiology or Medicine. They earned it for discovering and developing avermectin, the natural version of ivermectin, from a single soil sample dug up at a Japanese golf course. Later Campbell and some associates modified avermectin to create ivermectin. The FDA has approved ivermectin as a safe and effective anti-parasitic in humans and animals. Merck has donated four billion doses of ivermectin to prevent river blindness and other diseases in areas of the world, such as Africa, where parasites are common.[1] Ivermectin has been used safely in pregnant women, children, and infants.[2] Ivermectin is on the WHO’s List of Essential Medicines. The Front Line Covid-19 Critical Care Alliance calls ivermectin “one of the safest, low-cost, and widely available drugs in the history of medicine.”[3]
Merck’s patent on ivermectin has long since expired. But what if it were still in effect?
Starting in 2012, ivermectin’s potential against viruses was becoming known. Its ability to act against 21 viruses, including SARS-CoV-2, the cause of COVID-19, is documented.[4] In one in vitro study, a single dose reduced the viral load of SARS-CoV-2 in cells by 99.8% in 24 hours and 99.98% in 48 hours.[5] Ivermectin later showed in vivo efficacy. Ivermectin demonstrated effectiveness against SARS-CoV-2 in three clinical trials by August 2020, about half a year into the pandemic.[6]
Had ivermectin still been patent protected and Merck could have benefited financially, Merck could have asked the FDA for either a full approval or an emergency use authorization for the treatment of patients suffering from SARS-CoV-2. I have little doubt that the FDA would have acted quickly given the seriousness of the pandemic.
According to the World Health Organization’s COVID-19 dashboard, there have been 7 million COVID-19 deaths worldwide.[7] (The WHO estimates there have been 15 million “excess deaths” from the pandemic through the end of 2021.)[8] Based on all the clinical evidence compiled, which includes 100 clinical trials involving 138,284 patients, ivermectin treatment has reduced mortality by 49%.[9]
Therefore, if we make the simplifying assumptions that no patients received effective treatments and they all could have received ivermectin, then the upper limit for lives saved is 3.5 million.
That’s the hypothetical. What actually happened?
The FDA issued a special statement warning that “you should not use ivermectin to treat or prevent COVID-19.”[10] The FDA’s warning, which included severe language such as, “serious harm,” “hospitalized,” “dangerous,” “very dangerous,” “seizures,” “coma and even death,” and “highly toxic,” might suggest to a reader that the FDA was warning against pills laced with poison. The FDA also claimed that ivermectin is not an antiviral, notwithstanding its known activity against 21 viruses. This special warning was taken seriously and used by many to argue that ivermectin had no benefit during the pandemic.
Merck, which was developing Lagevrio (molnupiravir) at the time, stated: “We do not believe that the data available support the safety and efficacy of ivermectin beyond the doses and populations indicated in the regulatory agency-approved prescribing information.”[11] Many interpreted this to mean that even the company that developed ivermectin thought that it doesn’t work for COVID-19.
That’s not how the FDA-regulated pharmaceutical industry works. Merck had two good reasons to disparage ivermectin. First, Merck was developing Lagevrio, which it hoped would be a good, patent protected treatment for COVID-19, and analysts were predicting multi-billion-dollar sales for it.[12] Second, while off-label prescribing is widespread and completely legal, it is illegal for a pharmaceutical company to promote off-label uses. Doctors can use drugs for off-label uses (those not listed on the FDA-approved “label”) and drug companies can supply them with product. But heaven forbid that companies encourage, support, or promote off-label prescribing. The fines for doing so can be outrageous. Merck’s lawyers, aware of the penalties, avoided even the suggestion that ivermectin could be used for COVID-19. To do otherwise could have been seen as encouraging off-label prescribing.
Lagevrio, unfortunately, never measured up. The clinical data showed that Lagevrio prevented only 23% of deaths.[13] Worse, Lagevrio has a troubling safety record because it can lead to mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity. In plain English, Lagevrio can alter human DNA. Compare that to ivermectin that has been used safely by pregnant women, children, and infants.
I’m not saying this closes the conversation about the merits of patents for pharmaceuticals. But here is an example of one patent, that had it been in effect during the pandemic, could have potentially saved millions of lives.
In summary, because of patent laws, Merck saw no benefit from developing the more promising and more widely studied ivermectin for COVID-19, instead putting its efforts behind a drug that turned out to be dangerous. Ultimately, many died.
[1] Merck & Co. website: https://www.merck.com/stories/mectizan/
[2] Pierre Kory et al., “Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19,” American Journal of Therapeutics, May/June 2021.
[3] FLCCC Alliance Response to the NIH Guideline Committee Recommendation on Ivermectin use in COVID-19 dated January 14th, 2021
[4] D.A. Jans and K.M. Wagstaff, “The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2?,” Biochemical and Biophysical Research Communications, https://doi.org/10.1016/j.bbrc.2020.10.042
[5] Leon Caly, et al., “The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro,” Antiviral Research, Vol. 178, June 2020.
[6] https://c19ivm.org/meta.html
[7] https://data.who.int/dashboards/covid19/deaths?n=c
[8] https://www.nature.com/articles/s41586-022-05522-2
[9] https://c19ivm.org
[10] FDA consumer update, “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19,” on FDA website. Old version, before it was changed.
[11] https://www.merck.com/news/merck-statement-on-ivermectin-use-during-the-covid-19-pandemic/
[12] https://www.fiercepharma.com/pharma/merck-molnupiravir-blockbuster-covid-19-pandemic-endemic-oral-antivirals-market?mkt_tok=Mjk0LU1RRi0wNTYAAAF_-u5pJQfU10JOAhx04ROzWdkrVUuyeXVFt2Gg9yJe6033IW_jfPG5kQ44DSDybPn6ws8GpKMq9nlhni1m6q7tycZbpROoiIfUwpczBRtBC8RW0-Y&mrkid=644823
[13] https://c19ivm.org/m