‘The Splendid Gift from the Earth’-Ivermectin

Ivermectin

If you ever happen to visit the Carter Center in Atlanta, on its grounds you see the featured statue. It reminds us about one of the greatest ongoing battle of our times. It is not a battle about gore and killing but a battle about hope and about humanity and about why this world is a better place because of this fight.

The statue depicts a child leading a blind man with a stick. River blindness, a tropical disease which leads to progressive blindness such that the only humans left with intact sight in many villages are kids. The statue shows that in these villages where all adults are blind, children become their support as they lead them around to carry out their daily chores. Onchocerciasis or river blindness occurs where 120 million people in 36 countries are at risk- 18 million are infected- 770,000 are infected/ disabled.

Here is this remarkable story which will restore our faith in humanity. A story which shines light on  one of the finest public-health success stories of the past century and serves as a model for all future public and private sector partnerships.

[World Bank]

1971-

A 38-years old Japanese scientist with doctorates degrees in chemistry and pharmaceutical sciences from the Kitasato Institute, Japan is on a sabbatical at Wesleyan (named after John Wesley, the founder of Methodism-a story for some other time) -a college on a hill overlooking the Connecticut river. His name- Satoshi Ōmura.

Among his belongings he brings to Wesleyan are a number of extracts from soil samples from near the golf course course bordering the ocean at Kawana, near Ito City in the Shizuoka region where Satoshi loved to golf. He plans to continue his work on analyzing the soil extracts for anything of interest- naturally-occurring bacteria that could be medicinally beneficial. Here he works with Max Tishler.

One day within a few months of arriving in Wesleyan, an entry on his lab book shows a lot of scientific writing in Japanese but also has a series of exclamation points.  The significance was clear. Omura had discovered something of utility and importance-the stuff from the microorganism Streptomyces avermitilis, which was highly potent against a wide variety of bacteria. A chemical with significant antiparasitic effects, which they called Avermectin- the precursor for the drug Ivermectin (trade name Mectizan).

Tishler, who joined Wesleyan’s faculty after retiring as senior vice president of research and development at the pharmaceutical company Merck & Co., introduced Omura to contacts at Merck which sets up a collaboration.

1974

Dr. William Campbell, a veterinarian researcher at the Merck laboratories in Rahway, New Jersey,  receives 54 samples from the Ōmura’s laboratory at the Kitsato Institute in Japan. As Merck researchers methodically put the soil through hundreds of tests, Merck scientists were pleasantly surprised to detect strong antiparasitic activity in Sample No. OS3153, a scoop of soil dug up at a golf course near Ito, Japan. One of them contains a factor with significant antiparasitic effects, they would later call Avermectin. Campbell’s team isolated avermectins from the bacterial cultures and tweaked the structure of one of the most promising compounds to develop it into a drug — ivermectin.

1979-

Initially for use in animals, Dr Campbell’s team realize that ivermectin may be effective against river blindness.  The company began seriously to consider the potential use of ivermectin in humans. It was brought to the attention of P. Roy Vaeglos, M.D. president of the Merck Research Laboratories. Dr Mohammad Aziz, a clinical researcher at Merck, having worked in the World Health Organization  (WHO) conducted the first human clinical trial on February 24, 1981 in Dakar, Senegal when the first patient receives a single oral dose of Mectizan (hear video interview of Dr Vagelos below).

Ivermectin proved to be remarkably effective in humans, leading to a hope that the cure for river blindness was possible. As soon as data on the compound’s safety and effectiveness became convincing, Merck contacted the World Health Organization. At first the World Health Organization did not believe the inital results and was not particularly interested in the drug due to its inability to kill adult worms and its own interests in controlling River Blindness through the use of black fly insecticides.

Due to its continued effectiveness in clinical trials, the WHO’s position changed so that in 1982, Merck and WHO began a collaborative ivermectin research program under the guidance of Drs. Mohammed Aziz and Kenneth Brown. In the next few years, trials were conducted in Ghana, Guatemla, Cote d’Ivoire, Liberia, Mali, Senegal and Togo.

1987-

These efforts culminated in the approval of the Mectizan in France in 1987.

The development of Ivermectin, however raised major hurdles around the problem of how affected populations could receive the therapy. The challenge for Merck and the World health Organization then became finding a way to distribute Mectizan to millions in the 35 endemic countries that needed it – many of whom had little access to modern means of communication and lived in extreme remote regions in regions of strife and war.  Who would pay for the cost of the medication? What would be the company’s liability if some previously undetected side effects occurred with widespread use? Would donation of this new drug prompt a decrease in research on antiparasitic medications if companies were expected to donate the products of such research efforts? 

Merck exhausted all third party payers as intermediaries for donation of ivermectin including the World Health Organization, the U.S. Agency for International Development, and the U.S. Department of State. In meetings with both the Deputy Secretary of State and Chief of Staff, Dr. Vagelos was told that the humanitarian effort was worthwhile but no money was available for the program to supply the drug at cost. U.S. Senators Bill Bradley, Frank Lautenberg, Edward Kennedy and Richard Lugar even supported congressional action to sponsor the worldwide distribution of Mectizan. However, no one offered sufficient assistance to meet the need, so at this point in 1987, after receipt of consent from the Kitasato Institute, which agreed to forego royalties, Merck chairman Dr. Roy Vagelos decreed that Merck would donate Ivermectin-free of charge-to those who needed it for as long as it was needed, a pledge that has been honored ever since. 

Since 1987, the Mectizan Donation Program has given out more than a billion treatments for onchoceriasis and lymphatic filariasis to people in 33 countries. As a result, the transmission of onchoceriasis has been stopped in many countries. Last year Ecuador became the second affected country, after Colombia, to entirely eradicate the disease. The WHO forecasts that both diseases could be eradicated by 2020.

Before this, no large pharmaceutical company had ever given away a drug they developed to eradicate a disease. At a news conference after Merck’s announcement, the late Massachusetts senator Ted Kennedy said, “Merck’s gift to the World Health Organization is more than a medical breakthrough–it is truly a triumph of the human spirit.” Merck, continues to pay for the production costs of Mectizan, the costs of transport from the manufacturing facility in France to the recipient countries and the related customs and other handling costs. 

 George W. Merck, son of the company’s founder and its former chairman, said these inspirational words  “We try never to forget that medicine is for the people,” Merck said.  “It is not for the profits.  The profits follow, and if we have remembered that, they have never failed to appear.  The better we have remembered it, the larger they have been.”  These words formed the basis of Merck’s overall corporate philosophy.

As one of the greatest achievement of the twentieth century the ivermectin is a story of triumph of the human spirit, allaying  untold misery in the developing world. This collective effort was recognized as William C. Campbell and Satoshi Ōmura were awarded one half of the 2015 Nobel Prize  in Physiology or Medicine 2015   “for their discoveries concerning a novel therapy against infections caused by roundworm parasites” “

Ōmura in his aptly titled Nobel Prize lecture ‘ ‘The Splendid Gift from the Earth’ hopes that the publicity will help refocus us on the idea that the immense diversity of products out there in the natural world is a great starting point for drug discovery.

 

“We can choose to alleviate suffering. We can choose to work together for peace. We can make these changes — and we must.” 

-Jimmy Carter, 2002 Nobel Peace 

 

36:17 minutes onwards- Ivermectin

 

Reference:

Nobel Prize and Merck webpages

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