Malaria may spike in India as coronavirus cases rise globally
March 30, 2020: Novartis today shipped its first batch of generic hydroxychloroquine sulfate in the United States to be used to treat patients infected by the coronavirus, COVID-19. It marks the start of the Swiss company’s donation of 30 million doses to the U.S. department of health, and is part of its commitment to donate a total 130 million doses globally by May.
However hydroxychloroquine has not been tested for effectiveness, toxicity and side-effects in clinical trials for treating COVID-19, a process that is normally required before a drug is granted approval for sale by the FDA. Yet the formulation is being aggressively used by the U.S.,as well as France, China and other governments to treat coronavirus patients. Such use, officials expect, will also serve as a clinical study as part of the drug’s formal approval process.
Hydroxychloroquin used to treat malaria since the 1940’s
Novartis also makes chloroquine phosphate which is also being used in the treatment of the pandemic virus. It is an older drug, in use since the 1930’s, with more side effects. Hydroxychloroquine sulfate has been used as a drug since the 1940’s. The two drugs have long been approved to treat malaria around the world, including in India. Hydroxychloroquine is also effective in the case of adult patients with some autoimmune diseases including systemic lupus erythematosis and rheumatoid arthritis.
They are both generic drugs, with patent protections having expired, and so can be made by any drug company without permission and royalty payments to the original manufacturer. The price of Hydroxychloroquine, used to treat malaria, is relatively low. It can be produced in very large quantities but drug companies are reluctant since the profits on generics are typically smaller than those on patented drugs. Also, in normal market circumstances, they fear that expanding supply would lead to lower prices.
President Trump differs with medical experts on coronavirus treatment
Since the rapid spread of the coronavirus in the U.S. in recent weeks, President Donald Trump has repeatedly said he expects Hydroxychloroquine - as well as Remdesivir an anti-viral made by Gilead - to be very effective in treating COVID-19 patients. In contrast, Dr. Anthony Fauci and Dr. Scott Gottlieb are doubtful about the outcome. Both of them are medical experts with good reputations gained while successfully leading U.S. efforts to limit the impact of earlier infections like AIDS and Ebola.
Dr. Fauci is the director of the National Institute of Allergy and Infectious Diseases and Dr. Gottlieb was the former head of the U.S. Food & Drug Administration. In media interviews, both of them have said that while Hydroxychloroquine may have worked in laboratory test tubes, there needs to be clinical trials with human patients to see if it can safely treat coronavirus patients on a large scale.
While known to be generally safe in mild to moderate doses, high doses of the formulation can be toxic. Side effects range from diarrhea and dizziness to hypoglycemia and, more rarely, symptoms of heart failure. It could also cause damage to the retina, especially when used at higher doses, for longer times and with certain other medicines such as the breast cancer drug tamoxifen.
Pharmacists fear customers walking in with guns to get hydroxychloroquin
With the sudden, sharp spurt in demand for hydroxychloroquine to treat COVID-19 patients, and limited supply, there are reports of a growing shortage of the drug needed to treat diseases for which it has long been used. Also there are reports of a sharp rise in the price of the drug due to hoarding and price gouging by unscrupulous businesses.
For instance, the Lupus Research Alliance, a lobbying group for lupus patients in the U.S., says there are shortages of the drug developing quickly. “In many pharmacies, especially in New York and California, the drug has been unavailable” for Lupus patients, the Alliance notes. Lupus is a chronic autoimmune disease that can affect the joints, skin, brain, lungs, kidneys, and blood vessels, causing widespread inflammation and tissue damage in the affected organ.
“A lot of pharmacists are worried …I never thought that we’d have to put drugs like these (hydroxychloroquine) in a safe and worry about people pulling guns” to get them, a San Francisco area pharmacist told medicinenet.com.
Malaria kills over 400,000 each year
In 2018, according to the World Health Organization, an estimated 228 million people suffered from malaria and about 405,000 died from it around the globe. More than 60% of the deaths were among children under five. Severe malaria can cause lifelong intellectual disabilities in children. The disease’s economic impact is billions of dollars in lost productivity every year, estimates the Bill and Melinda Gates Foundation. .
Malaria is caused by parasites transmitted by mosquitoes. Even in mild cases, it can cause high fever, chills, flu-like symptoms, and severe anemia. These symptoms can be dangerous for pregnant women and young children infected by the disease for the first time.
Malaria emerges each year primarily in Africa, which saw 93% of the deaths from the disease in 2018. The rest of the deaths occur in Asia, including India. In 2010, India had about 15 million cases of malaria in seven states and that too mainly in Jharkhand, West Bengal and Uttar Pradesh. The cases in India dropped to about six million in 2018, with West Bengal seeing a very sharp decline.
Shortage of hydroxychloroquine to treat malaria
Since 2000, deaths from malaria around the world have been reduced by half. The reduction was driven by a combination of effective drugs, such as hydroxychloroquine, and reliable diagnostic tests made possible by a rise in funding as well as intervention by governments in the affected countries, according to the Gates Foundation. The foundation has so far committed over $2.9 billion to tackle malaria.
While the diversion of hydohydroxychloroquine to treat COVID-19 in the U.S. and Western Europe has led to a shortage and spike in prices of the drug for lupus patients in those prosperous regions, the problem is far worse for malaria patients in India and other developing countries. When news of the diversion broke, The Wall Street Journal reported, people in South Asia and Africa rushed to stockpile the anti-malarial drug. Pharmacies were quickly emptied of the drug in Lagos, Kampala, Karachi and other cities, while several patients were hospitalized in Lagos after self-medicating, the newspaper reported.
The Indian government has recommended that health care workers take hydroxychloroquine to protect against the coronavirus. On March 25, India banned the exports of the drug to try to avoid domestic shortages. India has some of the world’s largest manufacturers of the drug as well as its ingredients. It remains to be seen if the supplies are adequate and sold at prices that will prevent a resurgence in the number of cases and deaths from malaria in India. It is also possible that severe cases of malaria will spike just as there is a sharp rise in the number infected by the coronavirus.
Vasant Narasimhan chief executive of Novartis
Novartis, which makes Hydroxychloroquine, is led by Dr. Vasant (Vas) Narasimhan. With $49 billion in revenues in 2019, the company is a global leader in generics and drugs similar to those with expired patents. In the U.S. it sells over a hundred drugs, including those for treating cancer, heart disease and viral infections. It has over 250 drugs in the pipeline and operates in 155 countries. It was formed in 1996 following the merger of Ciba-Geigy and Sandoz. Those roots of those companies go back to 1895. Novartis has a stock market value of $184 billion.
Trained as a medical doctor, Dr. Narasimhan has been Chief Executive Officer of the company since 2018. He has experience dealing with drugs for virus, including as head of the company’s vaccine division from 2012 to 2014 and as head of its U.S. vaccines diagnostics from 2008 to 2012. During his career at Novartis, Dr. Narasimhan has overseen the licensing of over 20 novel medicines, including cell and gene therapies as well as vaccines. During and after his medical studies, he worked extensively on a range of public health issues in low- and middle-income countries, according to the company.
Before being appointed chief executive, Narasimhan was global head of drug development and chief medical officer of Novartis from 2016 to 2018. Earlier he held a range of leadership roles at the company including as global head of pharmaceuticals from 2014 to 2016. While he has been CEO, Novartis has completed over $70 billion in business transactions.
Narasimhan received his doctor of medicine from Harvard Medical School, a master’s degree in public policy from Harvard’s John F. Kennedy School of Government, and a bachelor’s degree in biological sciences from the University of Chicago. He is a member of the board of fellows of Harvard Medical School.
Subsequent developments
Study finds no benefit, higher death rate in patients taking hydroxychloroquine for Covid-19
How false hopes spread about hydroxychloroquinine as a cure for coronavirus, from The Washington Post 4.13.2020:
Using threat of retaliation, President Trump pushes India to resume chloroquinine exports to the U.S. See this April 7, 2020 story in The Guardian:
How Chloroquinine attracted attention as a possible cure for coronavirus. The Wired, March 19, 2020