The story of Hydroxychloroquine began in 1638 when the wife of the Viceroy of Peru acquired malaria. She was treated by an Incan herbalist with the bark of a tree and she recovered dramatically. When the Viceroy returned to Spain, he brought with him large supplies of the bark powder for general use, which at the time was controlled by the Church and was thus called “Jesuit’s Powder”. It took nearly two centuries for the active substance, Quinine, to be isolated from the bark. Over the next century, quinine became a common component in folk medicines and patent remedies for the treatment of malaria in the southern states of America. By the 1940s, quinine and its derivative chloroquine(C18H26ClN3), was recognized for its anti-malarial properties and found use among troops fighting in the Pacific during World War II. However, it was noted that this compound had significant toxicities. In 1945, a modification of this compound via hydroxylation led to the development of Hydroxychloroquine(C18H26ClN3O), which was found to be less toxic and remains in use, without change, to this day. Hydroxychloroquine was approved for medical use in the United States in 1955. Today, Chloroquine is used to prevent and treat malaria and amebiasis while hydroxychloroquine is used to treat malaria as well as rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis and Sjogren's syndrome. Sold under the brand name of Plaquenil, it is on the World Health Organization's List of Essential Medicines. In 2017, Hydroxychloroquine was the 128th-most-prescribed medication in the United States, with more than five million prescriptions.
Recently, Hydroxychloroquine has been floated as a potential treatment candidate to treat COVID-19. Though the result of studies related to the effectiveness of Hydroxychloroquine has not been unanimous, some studies has shown it to block viruses from binding to human cells and getting inside them to replicate. Thus, it improves the success rate of treatment and shorten hospital stay. Moreover, combining hydroxychloroquine with the antibiotic azithromycin has also generated positive patient outcomes. Further, US President Donald Trump’s campaigning for Hydroxychloroquine and US FDA’s approval for emergency use of these drugs has led to a surge in global demand for the inexpensive drug.
India is the world’s largest producer of hydroxychloroquine and exported $51 million worth of the drug in FY19. Nearly half the supply of hydroxychloroquine to the U.S. comes from makers in India (Dr. Reddy’s Laboratories & Zydus). The top U.S. supplier of hydroxychloroquine, Zydus Pharmaceuticals Inc., is a subsidiary of India-based Cadila Healthcare Ltd. It sold over 167 million units of the anti-malarial in 2019 and has supplied 28 million integrated units to retail and institutional channels in the U.S. so far this year. Prasco Labs, situated in Cincinnati, is the largest producer of hydroxychloroquine in US. Seminal Patents
1. US2546658A: 7-chloro-4-[5-(n-ethyl-n-2-hydroxyethylamino)-2-pentyl] aminoquinoline, its acid addition salts, and method of preparation Application Date: July 23, 1949 Grant Date: March 27, 1951 Current Assignee: STWB Inc This patent proposes a method to prepare 7-chloro-4-(5-(N- ethyl-N - 2 - hydroxyethylamino)-2-pentyl) aminoquinoline. The compound is useful as an antimalarial agent and can be used either in the free base form or in the form of its acid-addition salts.
2. US5314894A: (S)-(+)-hydroxychloroquine Application Date: Sep 15, 1992 Grant Date: May 24, 1994 Current Assignee: Sanofi SA The invention proposes compositions of hydroxychloroquine which is useful in the treatment of acute attacks and suppression of malaria due to Plasmodium, susceptible strains of Plasmodium falciparum, systemic and discoid lupus erythematosus, and rheumatoid arthritis. 3. US6572858B1: Uses for anti-malarial therapeutic agents Application Date: May 1, 2000 Grant Date: June 3, 2003 Current Assignee: APT Pharmaceuticals, LLC The patent provides a method to treat inflammatory diseases via local delivery to the patient of a composition containing an anti-malarial agent such as hydroxychloroquine. 4. US20040167162A1: Uses for anti-malarial therapeutic agents Application Date: May 1, 2000 Current Assignee: APT Pharmaceuticals, LLC The patent application proposes a method for the treatment of an infection in a mammal of a virus by targeted delivery of aminoquinoline or hydroxyquinoline, wherein the virus is adenovirus, rhinovirus, human corona virus or influenza virus. 5. US7553844B2: Methods for treatment of HIV or malaria using combinations of chloroquine and protease inhibitors Application Date: Feb 20, 2004 Grant Date: June 30, 2009 Current Assignee: Jarrow Formulas Inc The invention relates to a drug combination capable of conferring therapeutic benefits in the treatment of both AIDS and malaria. In particular, it relates to a drug combination including at least one quinolinic antimalarial compound such as chloroquine or hydroxychloroquine, and at least one inhibitor of the Human Immunodeficiency Virus (HIV) protease enzyme. This drug combination is capable of inhibiting the replication of both HIV and Plasmodium sp. It also relates to the direct antimalarial effects of the HIV PIs.