Repurposing Medications: Reimagining Treatment Options

Last month around the Chinese New Year holiday, a prominent Chinese scientist from Guangzhou Medical University made an announcement that stirred controversy both domestically and internationally while also highlighting a route to combat ailments that global academia and pharmaceutical industries have been attracted to for years. The scientist revealed that his team had been injecting patients with a malaria-causing parasite in order to cure a range of cancers – with two patients seeming to have no cancer cells remaining at the site of tumor and five additional patients having no disease progression out of ten total patients receiving this malarial therapy for at least a year. Although this type of treatment has been attempted in the past in an attempt to combat HIV in the 1990s, the Centers for Disease Control (CDC) and other health governing bodies determined that there was insufficient pre-clinical data to justify human trials during this time period. The controversy revolving around this announcement encompasses the aforementioned determination by CDC, the release of trial results before being published in a peer-reviewed journal, and, most importantly, the possibility of creating a malaria public health emergency for a country due to eradicate the communicable disease by 2020. Although the scientist who underwent this study clearly abdicated internationally conferred health principles, this avenue of repurposing – repositioning, re-profiling, re-tasking, etc – medications and therapy is becoming more appealing to those invested in novel treatment options for both established and emerging diseases.

Throughout the development lifecycle of new chemical entity (NCE), the process for regulatory approval could span over ten to fifteen years with an associated cost of over 2 billion dollars. This has led to an average of only 20 to 30 NCEs being approved by the Food & Drug Administration (FDA) each year. However, through repurposing medications, the development span can be cut to five to eight years at approximately 60% of the total NCE cost – in addition to higher approval rates from regulatory agencies. This repurposing process, as shown by the statistics, is enormously appealing for pharmaceutical companies/investors, but also provides targeted therapy for patient’s disease states at a theoretically lower price than an NCE. Even for rare genetic diseases, repurposing has become common due to only 400 medications being on the market to treat over 7000 genetic conditions. Repurposing is accomplished through the theory of translational research which takes a look at basic scientific discoveries and determining how a medication can be made to match this discovery – for example, examining the molecular pathway of diabetes and then matching it with a chemical entity that has an effect within the pathway like glucagon-like peptide 1 (GLP-1). The known chemical entities are commonly stored in giant databases within academia and the industry. Through big-data analytics, advanced modeling, and high throughput screening techniques, these chemical entities can then be extracted from the databases and determined if it has a possible role in a certain molecular pathway.

This method of establishing novel treatment options ought to be utilized more frequently and effectively, though there are medications over the years that have undergone this type of approval. The following are examples of already approved medications and others undergoing clinical trials:

Approved Repurposed Medications:

  1. Thalidomide, which was originally developed as a racemic mixture of enantiomers for the treatment of morning sickness but found to be teratogenic due to the effect of the (S)-isomer, was later successfully developed by Celgene as a single (R)-isomer product for the treatment of leprosy and multiple myeloma.
  2. Viagra (Pfizer’s sildenafil) was a drug that initially failed as an angina treatment in clinical studies; however, during these trials, its effect on erectile dysfunction was noted and then later approved for this indication.
  3. Celebrex, commonly used in osteoarthritis, works by inhibiting COX-2 receptors. Recently it has been shown that for patients that previously had colon cancer, taking this agent can reduce the risk of additional polyp formation without negative gastrointestinal effects associated with existing treatments.
  4. All-trans retinoic acid (ATRA), which is an acne medication, when combined with traditional chemotherapy, results in complete remission of acute promyelocytic leukemia in 90% of treated patients.
  5. Tamoxifen, a hormone therapy medication, treats metastatic breast cancers, or those that have spread to other parts of the body, in both women and men, and it was originally approved in 1977. Thirty years later, researchers discovered that it also helps people with bipolar disorder by blocking the enzyme PKC, which goes into overdrive during the manic phase of the disorder.
  6. Raloxifene was initially developed to treat osteoporosis, but has since been shown to reduce the risk of invasive breast cancer in postmenopausal women in 2007.
  7. Zidovudine (AZT) was initially developed to treat various types of cancer, but was determined to be ineffective. However, it was repurposed into the first approved HIV/AIDs medications in 1987 and has had a tremendous impact on the progression of the autoimmune disorder.

Repurposed Medications Undergoing Clinical Trials:

  1. The lipid soluble simvastatin is currently undergoing a trial in the UK to assess the efficacy of reducing the progression of Parkinson’s disease. The statin drug class is thought to prevent this ailment through its pleiotropic effects including reducing inflammation, reducing oxidative stress, reducing the formation of sticky bundles of alpha-synuclein, and increasing the production of neurotrophic factors. The results are expected to be released in 2020.
  2. Purdue University received a grant from the National Institutes of Health (NIH) to discover the effectiveness of Ebselen, a chemical entity, against methicillin-resistant Staphylococcus aureus (MRSA), and auranofin, which is FDA-approved for the treatment of unresponsive rheumatoid arthritis, against Clostridium difficile.
  3. Metformin, a first line agent for many diabetics, has been shown to reduce the risk of breast cancer in diabetes patients and is being investigated as a treatment for cancer in many different clinical trials

Although this is certainly not an exhaustible list of the impacts repurposing has had on healthcare, the majority of this repurposing stems from serendipitous observations rather than targeted interventions. Through these unanticipated occurrences, a range of disease states can now be more effectively treated ranging from communicable diseases like HIV/AIDS to mental health ailments including bipolar disorder and Parkinson’s disease to non-communicable diseases. As the rising cost of healthcare continues to devastate humanity and lead to health inequalities, heads of governments, pharmaceutical industries, academia, and nonprofits need to commit themselves into investing their time and resources into this repurposing method. The targeted repurposing interventions are more vital and should be devoted to in order to expand options for health disorders rather than the unexpected observed effects. The financial and health outcomes will lead to novel treatment options accessible to a majority of the world which will allow health care professionals to properly accompany their patients through their disease state.

It’s National Public Health Week!

From the National Public Health Week Website: http://www.nphw.org/

We hope you’ll take advantage of all National Public Health Week 2019 has to offer as we celebrate public health and highlight key issues. During these seven days of inspiring events, conversations and celebrations nationwide, don’t miss:

  • Our annual Twitter chat, a conversation with public health leaders from around the country. Mark your calendar for April 3, and don’t forget to RSVP.
  • The NPHW Forum on April 1 featuring grassroots organizers sharing how they’ve activated their communities to improve health right where they live. You can register to attend in person or watch the event via webcast.
  • NPHW’s Student Day discussion on April 4, when public health professionals will share tips on how to break into the field. You can join us in D.C. or watch the webcast to ask questions about getting that first job out of school.
  • Our Shareables page featuring images you can post on social media and NPHW logos to help you spread the word about NPHW 2019.
  • NPHW events in your community, from fundraising fitness walks to health fairs to educational workshops. You can search by state on our Events page.

Our fact sheets are available year-round on the NPHW website so we can keep the momentum and learning going. Learn more about this year’s daily themes and how you can be part of the movement for science, action and health.

Why do we celebrate National Public Health Week? APHA Executive Director Georges Benjamin explains that perfectly in his NPHW 2019 Welcome Letter.

Read the inaugural issue of the IH Section’s Climate Change and Health Newsletter!

The IH CC&H Working Group is pleased to share our first newsletter.

We plan to publish every other month and will highlight cutting edge best health practices in climate change.  It will also spotlight our IH members engaged in adaptation and mitigation practices with links to internationally focused resources.  The IHCC&WG newsletter will update readers on our progress on the country specific inventory of programs of NGOs, governments and donors engaged in climate change and health adaptation in developing countries.

Please take a few moments and fill out our survey to help us better disseminate information regarding climate change: https://docs.google.com/forms/d/e/1FAIpQLSfp-FZEi0DRU44PLD0ukLF2DxJbj5IwfKXYG6pY15kq5HCubg/viewform.

For additional information contact the IH CC&H WG at ihsection.cch@gmail.com

Kaiser Family Foundation releases budget summary analyzing global health-related funding in FY20 budget request

KFF released a budget summary analyzing global health-related funding contained in the FY20 budget request. The analysis includes a table that compares U.S. global health funding in the FY20 request to the FY19 request and enacted levels. It will be updated as more information becomes available.

https://http://www.kff.org/news-summary/white-house-releases-fy20-budget-request/

The Forgotten Health Inequality: Languages and Medical Information

Health inequalities and disparities have plagued this fragile earth since the beginning of unprecedented medical advances, the wealth divide, and the transition from agricultural economies to industrialized states. These health inequalities can range from lack of access to diagnosing technology, unaffordable medications that treat ubiquitous ailments, and distribution barriers that cause a shortage of preventive tools and drugs. Each one of these entities cause an immense amount of suffering for both health care providers, who are required to overcome the barriers, and, for those who are directly afflicted – patients and their families. In addition to these aforementioned health inequalities, the distribution of medical information is directly affected by another concealed yet detrimental form of disparity: the lack of diversity within the languages it is presented in.

Those who inherently speak English won’t face the same barriers as a rural Brazilian physician being unable to fully comprehend English specific instructions for a novel diagnosing tool for the Zika Virus. Nor will those inhabiting anglophone countries endure the same struggle of a Burmese pharmacist who isn’t able to utilize the pharmacokinetic data from a recently approved medication for colon cancer. The fact that information in English related to lifestyle changes for coronary heart disease might not be clear to some community health workers may not be realized from those hailing from the developed world where English is commonly spoken. Treatment guidelines, publications in prominent internationally renowned journals, medication inserts, and countless other resources are typically exclusively published in the English language – creating an insurmountable barrier for those having little access to an English medical education. While having a universal language like English as a connecting tool for the international health community has several benefits, this encompasses a little more than a billion fluent/semi-fluent English-speaking individuals on this earth: leaving about 6 billion humans with little or without access to this rich collection of health information. This language barrier for the majority of humanity amplifies the problems with the quality of care a health care provider is able to administer when also considering other health disparities like lack of access to technology and medications.

This disparity infects and disrupts many facets of the global health communities desire to truly empower local health care professionals and create sustainable public health care institutions. Although the leading global health entity, the World Health Organization (WHO), has attempted to tackle this disparity and expand its impact through diversifying its official languages, it still leaves half of the world population without access in their native tongue. The official languages of the WHO include Arabic (242 million native speakers), Chinese (1197 million), English (335 million), French (76 million), Russian (16 million), and Spanish (399 million) which totals to be only approximately 2.4 billion people. Furthermore, even with these six official languages, only WHO official documents are translated into the six languages while technical reports, guidelines and even the majority of the website is strictly in the English language. Besides WHO and as previously mentioned, the venues novel information is presented in like journals/guidelines is inaccessible to the great majority of health care professionals attempting to provide evidence-based care for their patients. A study published in Deutsches Ärzteblatt International in 2008 revealed that the amount of English-only journals in Medline has risen to 89% with roughly 9/10 new journals with Medline are in the English language. In addition, of 103 journals that are ranked and listed based on frequency of being cited, only 13 are not written (entirely or primarily) in English. This remote information can lead to situations where proper treatment guidelines are not followed causing morbidity or mortality, a lack of awareness of a necessary change within a hospital system, and other negative events that prevents local health leaders from taking charge of their community’s health and creating maintainable interventions.

Although making this medical information accessible to a superior majority of humanity is a difficult task due to lack of awareness, cultural aspects in languages, funding, and human resources, several programs have been recently developed throughout the world to begin addressing this health inequality with the assistance of WHO and political will:

    • In 2009, King Saud bin Abdulaziz University of Health Sciences in Saudi Arabia conducted a study that revealed that just over 4% of all Arabic health information websites met international quality standards. With this data being brought forth, the WHO’s Global Arabic Program was established to disseminate the work of WHO through Arabic publications, make reliable and current health information and research outcomes available in Arabic, and establish networks and knowledge communities in Arabic translation, terminology and publishing. In addition to this WHO program, an establishment of an Arabic health information foundation was created to govern and accredit Arabic health websites and an Arabic health encyclopedia
    • In 2012, WHO established a program, called the WHO Moscow documentation centre, which was funded by the Russian government to increase the number of technical WHO publications in Russian, such as clinical guidelines, and to establish a mechanism for consulting Russian-speaking public health experts on which publications they needed most. In order to ensure proper translation and clinical effectiveness, Russian experts are also invited to review the Russian publications before being revealed. This has directly empowered local health care providers and has provided a sustainable foundation for future Russian health dissemination success.  
  • In 2005, WHO established the ePORTUGUESe program to increase access to health information in Portuguese as part of a collaboration with Angola, Brazil, Cabo Verde, Guinea Bissau, Mozambique, Portugal, Sao Tome & Principe and Timor-Leste. This has allowed each country to develop their own specific health information library to meet specific needs for their populations. This platform can be accessed by anyone with an internet connection, giving health care providers a venue to improve patient care.

These are promising starts to addressing the language barriers that affect health care providers each day while caring for their patients. However, a continued devotion for assisting Khmer-speaking midwives in rural Cambodia utilizing a new birth spacing method, Creole-speaking pharmacists in Haiti checking for drug interactions between coumadin and levofloxacin, and Portuguese-speaking pediatricians in Mozambique deciding what dose of a powerful antibiotic to give needs to be followed through with to honor the global health’s community commitment to each other. While these examples serve as templates for success, an increase in awareness must be brought to the attention of heads of states and health leaders to ensure this health inequality is properly addressed. International health journals have the obligation to better structure their publications in order to make the information more language accessible; while local journals need to promote publications in the residential language to improve the provided health care in the area. The empowerment of public and private health care professionals is vital to the success of their country’s health, and overcoming the medical language barrier is the first step to achieving this.