Realizing the full potential of pharmaceutical industry partnerships

Successful partnerships between pharmaceutical companies and global health organizations have been increasing access to medicines and vaccines since the 1970s. From early partnerships in the Expanded Program on Immunization, to GAVI, the Vaccine Alliance and Access Accelerated the research-based pharmaceutical industry, which spends over $149 billion on research and development (R&D) every year, has an important role to play in global health.

Over the last 50 years the pharmaceutical industry has learned that global health is about more than just medicines and vaccines, and with the integrated nature of the Sustainable Development Goals, public-private partnerships are increasingly important. According to the International Federation of Pharmaceutical Manufacturers and Associations, the industry understands that global health requires building and supporting strong health systems, developing public health education and strengthening standards and regulations. This is why in 2018, 17 out of the 20 largest pharmaceutical companies (accounting for 70 percent of global pharmaceutical revenues) developed a business strategy, supported by goals and targets, to address access to medicines in low-and middle-income countries (LMICs), according to an Access to Medicine Foundation report

Good, but not good enough

However, much of the increased access to medicines has been made by a small percentage of pharmaceutical companies, and has overwhelmingly been focused on a handful of diseases. Of the 20 companies assessed by the Access to Medicine Foundation report, five companies (GlaxoSmithKline, Johnson & Johnson, Merck KGaA, Novartis and Sanofi) were found to be conducting 63 percent of R&D on products urgently needed by people in LMICS; and nearly all of the R&D from these companies was focused on five diseases: malaria, HIV/AIDS, tuberculosis, Chagas disease and leishmaniasis. 

While overall, pharmaceutical companies are entering LMIC markets, the industry still puts profits first.  Between 2008 and 2018 more medicines for profitable non-communicable diseases were developed for people in high-income countries, than medicines for diseases of poverty. Additionally, only four out of 20 pharmaceutical companies supported international trade agreements designed to ensure the world’s poor benefit from innovative medicines and vaccines. 

Closing the gaps

Public perception does matter to the pharmaceutical industry. According to the Reputation Institute, between 2017 and 2018 the pharmaceutical industry saw a 3.7 percent decline in its reputation score, and overall the industry had a significant decline in the public’s perception of industry transparency, openness and authenticity. The decline of public trust and confidence in the industry has also led to a decline in the public’s willingness to buy by eight percent between 2017 and 2018. One way to improve company reputation is through global health partnerships, and with recent negative media attention on the industry, between the opioid epidemic and price-fixing drugs, it is no secret that the industry could use a reputation boost.

So how can the global health community capitalize on this? The Access to Medicines Foundation has an effective recipe for engaging pharmaceutical companies in global health: one, setting clear priorities endorsed by global health experts; two, advocating for publicly funded mechanisms to reduce investment risk and shape less profitable markets; and three, finding sustainable funding support from multiple donors, including the government. One example of a mutually beneficial partnership is GAVI, which used pooled procurement mechanisms to encourage pharmaceutical companies to enter fragile markets in LMICs to strengthen the global vaccine market. 

In 2018 the reputation scores for the top 22 pharmaceutical companies were made public, creating an opportunity for global health organizations to engage poorly ranked companies. Global pharmaceutical sales are expected to reach over $1 trillion by 2022, so resources for global health partnerships are abundant, and organizations should consider targeting partnerships with companies impacted by negative public perception; turning a bad reputation into increased affordable access to life-saving medications. 

 

Perspectives on Global Health from Pharmacists Around the World, Part Two

As healthcare continues to morph and adapt based on the requirements of kind, compassionate, evidence-based care, pharmacists are playing a vital role in ensuring patients needs are met in countless regions across the earth. In this four-part IH Blog series, the pharmacy role accompanied by profession-related challenges and pharmacist-led global health initiatives will be explored within a profession that is often underappreciated. The following perspectives, shared by practicing pharmacy professionals from the United Arab Emirates (UAE), Cambodia, and the United States of America (USA) aim at highlighting various aspects of healthcare that should be properly addressed by governmental bodies, NGOs, and all stakeholders by both sustainable political will and empowering solutions. 

This second installment focuses on medication quality in each of these areas and the thoughts that pharmacists from these respective nation states have been willing to share with IH Connect.

The onset of the biomedical and synthetic medication era brought with it a formerly unknown hope for the betterment of humanity’s health. The introduction of antibiotics like the beta-lactam class, vaccinations to completely eradicate diseases like smallpox, medications with unique mechanisms of action to regulate hypertension and diabetes, and more recently, targeted oncology medications to successfully attack cancer cells have all contributed to vastly improving patient care across the globe. However, with this tremendous advancement, novel complications have arisen that have plagued health care professionals in devastating arenas. For the pharmacy profession, specifically, the quality of medications has emerged as an additional concern in the treatment and dispensing process. Although a majority of nation states have regulatory bodies to monitor the quality of medications, low quality medications frequently find themselves in the hands of patients. This often leads to substandard care, furthers health inequalities, creates distrust in healthcare workers, promotes drug resistance, and damages the solemn promise every health care professional strives to follow – to properly care for those afflicted with various ailments. The perspectives and ideas that are shared in the following text explores medication quality throughout various parts of the world and initiatives that aim at addressing this determintental issue. 

Dr. Moeung Sotheara, Ph.D. 

Clinical Research Assistant & Part Time Lecturer – University of Health Sciences

Phnom Penh, Cambodia 

Access to high-quality medicines in many countries is largely hindered by the rampant circulation of counterfeit and substandard medicines. The use of counterfeit and substandard medicines represents a worldwide public health concern, and its prevalence is particularly high in developing countries. In Cambodia, the Ministry of Health reported in 2001 that 13% of medicines were spurious/falsely labeled/falsified/counterfeit, with 21% being substandard and 50% unregistered.

This crisis affects commonly used lifesaving medicines such as antibiotics, analgesics and anti-parasitics. The impact of poor-quality medicines is enormous ranging from increased adverse effects to increased morbidity and mortality. Poor-quality antimicrobials in particular has led to multi-drug-resistant malaria and bacterial infections which result in a huge burden for the country’s health sector. The high prevalence of poor-quality medicines has possibly contributed to the loss of confidence in health systems and health workers due to repeated treatment failure.

Among the reasons for the high rate of fake drugs in Cambodia are corruption, weak law enforcement, poverty and high sales taxes with self-medicating being often the driving force behind counterfeit drug markets. Counterfeit drugs mostly enter Cambodia through illegal drug outlets. The counterfeiting of drugs in Cambodia usually appears in the form of finished pharmaceuticals imported from neighboring countries, rather than the counterfeiting of bulk drug ingredients. This is due to the country’s lack of manufacturing capacity. Substandard drugs on the other hand are the result of limited implementation of good pharmacy practice regarding the distribution and the storage of pharmaceuticals which results in the deterioration in medicine quality.

Efforts have been made by the Cambodian government to tackle this problem. In 2015, the Cambodia Counter Counterfeit Committee (CCCC) was established and has been in charge of tracking counterfeit and substandard medicines circulating in the country. In 2018, the CCCC confiscated 138 types of illegal goods and substandard medication in 10465 packages from a pharmaceutical company in the capital city, Phnom Penh. The government is also working with its neighbors to decrease the number of fake drugs smuggled across the borders of Southeast Asia. Non-licensed drug outlets have been gradually disappearing, especially in the capital, either due to closure or accreditation, resulting from a strengthening of regulatory efforts. These initiatives are supported by pharmacists in communities by creating a front line against the distribution of counterfeits in the Kingdom through educating the public about the dangers of fake pharmaceuticals. 

Nazgul Bashir, B. Pharm

Registered Pharmacist – Super Care Pharmacy

Dubai, United Arab Emirates

Maintaining a healthy environment, reducing the healthcare cost, and using effective treatment options are all linked to medication quality. In any community, city, or region there are countless investments undertaken to improve the quality of healthcare overall. The Institute of Medicine defines health care quality as “ The degree to which healthcare services for individuals and populations increases the likelihood of desired health outcomes and are consistent with current professional knowledge.”

More specifically, medicine quality has two major roles: patient safety and effectiveness of treatment. Consuming a poor quality medicine will not only increase the risk to patient safety, but will hinder the proper treatment of patient. This can cause a patient to suffer more and increase the cost of treatment. Being a pharmacist and dispensing a low quality medication will also result in losing a patient’s trust. Since pharmacists have the role of dispensing medications, it is vital to ensure the medicine is in highest quality.

Quality of pharmaceutical products, mainly medicines, poses a serious challenge to the entire healthcare sector including drug manufacturers, distributors and dispensing pharmacists. According to the World Health Organization (WHO), the influx of fake or counterfeit medicine is a major concern in the market over all the globe.

Medicine in the United Arab Emirates (UAE) is manufactured so that medications go through systematic quality checks which are checked and re-checked several times while maintaining records in order to avoid any health hazard, Quality assurance teams then conduct self inspection or hire a third party to undertake inspections. The health regulations make sure that medicine distributed meet the standards of the listed quality and accepted internationally. On the other hand, imported medicines have similar criteria for safety and quality management. 

In order to further address low quality medications, the UAE Ministry of Health unveiled a new machine to detect imported drugs and inspect fake or counterfeit drugs. This machine is known as the TruScan RM Analyzer. It’s high tech detector is used to identify low quality drugs that pose health threats to the community. The device is helpful for chronic disease medicines such as diabetes, heart problems or even cancer drugs. The TruScan RM Analyzer also helps inspection regulators in the country to make informed and timely decisions for the release of drug shipments which are entering the country. In addition, UAE has been fighting the spread of low quality medicines in the country by taking many measures like high quality control labs and research on medicines and healthcare products.

Dr. Bryce Adams, Pharm D., RPh.

Oncology Medical Science Liaison

Washington D.C., United States of America

In the United States, the quality of medications isn’t commonly considered in the process of treating a patient. This is because of laws and regulations that are in place to ensure the quality of the medication. However, this wasn’t always the case. Up until 1906, there was no law requiring medications to be pure. That changed in 1906 with the passage of the Pure Food and Drug Act. This required medications to be labeled correctly and to meet purity standards put forth by the United States Pharmacopeia. 

This act greatly improved the quality of medications produced in the United States as manufacturers were required to list the ingredients that are used in the creation of medicine, and the ingredients and manufacturing process must meet certain standards. However, there is still a market for counterfeit medications as patients search for ways to reduce the cost of medications. It is estimated that 19 million US citizens purchase medicine outside of the current regulated system (e.g. from unlicensed sources such as foreign online pharmacies).  One recent example is with counterfeit Avastin, an anticancer drug, that was found to have no active ingredient. Another example is the recent opioid epidemic. Street drugs are being laced with fentanyl leading to increased overdoses and mortality. 

Recently, there have been discussions to allow for greater importation of medications into the United States. While this could potentially reduce the cost of medications, it could also increase the risk of counterfeit medications. Medications originating from outside of the United States makes it harder for the Food and Drug Administration (FDA) to regulate the quality and purity of medications. 

Patients in the United States can reduce the risk of receiving counterfeit medications by picking up their medications from their local pharmacy and can feel comfortable knowing those medications are of high quality. If cost is an issue, a patient can discuss their options with the pharmacist. There may be a cheaper alternative or an assistance program that can help offset the cost of the medication.

Perspectives on Global Health from Pharmacists Around the World

As healthcare continues to morph and adapt based on the requirements of kind, compassionate, evidence-based care, pharmacists are playing a vital role in ensuring patients needs are met in countless regions across the earth. In this four-part IH Blog series, these roles accompanied by profession-related challenges and pharmacist-led global health initiatives will be explored within a profession that is often underappreciated. The following perspectives, shared by practicing pharmacy professionals from the United Arab Emirates (UAE), India, Cambodia, and the United States of America (USA) aim at highlighting various aspects of healthcare that should be properly addressed by governmental bodies, NGOs, and all stakeholders by both sustainable political will and empowering solutions. This initial segment focuses on medication access in each of these areas and the thoughts that pharmacists from these respective nation states have been willing to share with IH Connect.

Throughout both developed and developing healthcare systems, access to medications is consistently a top priority for pharmacists and health care systems. As this health care profession attempts to provide services that meet the needs of their communities, access deficiencies habitually impede the ability to follow through with individualized and compassionate care. The lack of access to life altering chemical entities can affect anyone anywhere, from an affluent metropolitan city like Washington D.C. to a small rural Cambodian village in the province of Kampot. Despite the differences in these locations, each of these instances cause significant harm, breed mistrust in healthcare professionals, and create despair among those that seek healing. These frustrating situations are due to intensify because of the increased strain on medical resources who take a “do-what-has-always-been-done” approach. These following four pharmacists, all from various corners of this vast planet, will describe the barriers they consistently face regarding medication access and initiatives that are being undergone to ensure that a novel approach is commenced to address this looming medical tragedy.

Nazgul Bashir, B. Pharm

Registered Pharmacist – Super Care Pharmacy

Dubai, United Arab Emirates

Before discussing medication access in the United Arab Emirates, I would like to give a brief introduction about the United Arab Emirates (UAE). It is a middle eastern country with a population of 9.68 million. The country is comprised of seven emirates and healthcare in UAE is regulated both federally & at the Emirate level. 

Now, starting with the topic on hand about medication access in UAE, there are several factors that have an impact on it and I will touch on them individually and in detail. 

First and foremost, I think the most important factor is the number of medications available in UAE. The majority of medications available in UAE are imported drugs. UAE imports pharmaceutical products from 72 different countries. Of those, 10 countries constitute approximately 80% of the entire country’s supply. The domestic sector is rather small; however the UAE Ministry of Health (MOH) plans to increase the number of pharmaceutical manufacturing facilities to 30 by 2020 up from 16 in 2017. Availability of different medication combinations or different strengths are difficult to find due to the limited number of industries in UAE. One such example is oral prednisolone, which in UAE is available in strengths of 1mg, 5mg, 10mg & 20mg. In the USA, there are more strengths available including 1mg, 2.5mg, 5mg, 10mg, 20mg and 50mg. Tourists or expats coming from overseas that need a particular medicine or medicine combination or a particular strength may not find it available.

The second hindrance to medication access is the cost of medications. There are many reasons for the high cost medication. The aforementioned fact that about 80% of medications in UAE are being imported rather than locally manufactured is one reason. Another reason is an insignificant availability of generic medicines as the majority of medicines available are brand name. The final reason is the national health insurance model. Because all national citizens do not have to pay for their own medications, there is no incentive to keep the medicine prices low. As a result, individuals who are not insured under the public national insurance system, for example expats and tourists, face a huge barrier to obtaining medicines. 

With these barriers in mind, initiatives have started to take place in UAE to find a solution. The government reduced 24% of the prices for 8732 medicines over the course of 6 years. Another initiative which took place is increasing the number of generic medicines while also advising physicians and pharmacists to dispense the generic rather than the branded medicines. Through this initiative, generic medicines now account for 30% of the overall pharmaceutical market which has increased from 12% of the market two years ago. If the UAE can bump these numbers up to 70-80% of the overall market in UAE, the UAE will be seen in better position in terms of generic medicines. 

I am glad to be a part of a region where these issues are actively tackled, not just by the government but by private sectors as well. We are also seeing that pharmacists are playing a larger role, providing information on availability of cheaper alternatives on medicines. Pharmacists are the most accessible healthcare professional and it should be part of their responsibility to help make medicines as accessible as possible to their clients.

 Dr. Bryce Adams, Pharm D., RPh.

Oncology Medical Science Liaison

Washington D.C., United States of America

Although there are a host of issues surrounding access to medications, I will be focusing on oncology medications as oncology is my current specialty as a medical science liaison in the USA. 

To begin, I would like to highlight encouraging statistics that show the accessibility of oncology medications in the USA. A recent 2019 study found that 96% of new cancer medications were available within the United States, the next highest nation was at 71%. Furthermore, the average delay in the availability of cancer medications within the United States was 3 months, with the next closest nation being at 9 months.

In terms of novel and innovative treatment options, oncology drugs have been increasingly approved by the Food and Drug Administration (FDA) throughout the last few years. The FDA has enacted policy changes to attempt to increase the efficiency of drug reviews. The results have been significant – in 2017 alone, 46 new oncology drugs were approved. Moreover, from 1991 to 2016 there was a 27% decrease in cancer related deaths in large part to the expanded and more targeted-based therapy. The chance that a patient will live for 5 or more years has increased by 41% since 1975.

Outside of regular treatment options of those living with cancer, patients have the ability to participate in a clinical trial. Currently, there are 24,351 clinical trials listed as active (defined as not yet recruiting, recruiting, enrolling by invitation, or active) – 11,813 of those trials are active in the United States. However, even with the surplus of ongoing clinical trials, it still seems there is a lack of patient enrollment. It is estimated that roughly 70% of patients are interested in clinical trials, and yet <5% of patients actually enroll in clinical trials. Some of these barriers to enrollment include: lack of availability at a specific clinic, lack of a specific trial available, patient ineligibility, physician is unaware of trials/not offering them to patients, and a patient deciding not to enroll in a clinical trial (perhaps due to a fear of receiving the placebo).

An aforementioned barrier to cancer treatment that needs to be emphasized is the locations of specialized cancer clinics. Studies have shown that patients who are diagnosed with advanced staged cancer are likely required to drive an hour or more to the nearest cancer clinic for the appropriate care they need. Additionally, travel distance may affect treatment decisions. A patient may select a slightly less efficacious therapy if that means they have to travel less often. 

Two initiatives have recently been instituted to further increase the accessibility of medications. First, in an effort to go towards value-based contracting, some companies are beginning to only charge patients if their medications are effective. While this is a rarity, it will be interesting to follow the impacts of this on other more costly treatments and to determine the impact on patients. Secondly, in 2018, the right to try act was passed. This essentially gives terminally ill patients who are unable to enroll in a clinical trial and have no other remaining FDA approved options, access to other treatments. While this is a relatively new policy and there are some restrictions, hopefully it will give patients hope and additional treatment options. 

Dr. Moeung Sotheara, Ph.D. 

Clinical Research Assistant & Part Time Lecturer – University of Health Sciences

Phnom Penh, Cambodia 

In rural Cambodia, access to medication is especially limited when compared to urban areas. Access is limited by two main factors in these communities. Firstly, many people living in rural areas have low incomes which means it is difficult for poor rural individuals to buy medicines for serious illnesses. Secondly, community drug outlets and public health facilities are generally concentrated in the provincial capitals/cities, making it difficult for people from rural, remote areas to get access to those places. 

Usually, medicines imported from other Asian countries such as India, China, Vietnam, Thailand, or Malaysia are cheaper and therefore, more accessible. These cheaper medications, however, tend to be held toward a lower quality standard which can lead to disease state progression, antibiotic resistance, and other situations that can inflict harm onto patients. However, western brand medicines, which are usually held to a higher standard of quality, are less accessible because their prices are higher. Locally, they are generally considered “medicines for the rich.”

The lack of access due to  these aforementioned barriers makes diseases difficult or impossible to treat in cases where medication is necessary to cure it. Patients may see their disease aggravated and could die of it.

In order to address these medication access complications, a specialized team should be created that assists patients or their relatives to get medication which is far from their home and provide a specific loan with very low or no interest rate for villagers who cannot afford to buy medicines. This approach has been initiated in Cambodia through the increased access of health equity funds (HEF). These funds, allocated to individuals unable to afford the out-of-pocket expenses for public services, are pooled from a variety of sources like the national health budget and various donors. These patients are then given a specialized card to receive these funds when public services are used. The HEF focuses on addressing low medication access through the initial financing as aforementioned, community support, quality assurance, and finally policy dialogue. The results of this project have been promising – there was a 28% increase of patients utilizing public services with HEF than before without the HEF. In addition, the patients were not perceived to be more stigmatized within their communities.  

Veda Peddisetti, B. Pharm.

Clinical Pharmacist – Satya Sree Clinic & Diagnostics 

Hyderabad, India 

India is the largest country in South Asia and the second most populous country (1.35 billion) in the world. In addition, India is said to be in the third stage of demographic transition with birth rates declining and death rates decreasing. In the past few decades, India has experienced monumental population growth. This has led to many problems in healthcare management throughout the country, in particular, medication access. The direct cause seems to be the over-demand of medications. However, various indirect causes include poverty, varying per-capita incomes, unemployment, and out of pocket expenditures (India doesn’t have an established federal healthcare insurance system like Medicare in the USA, National Health Service in the United Kingdom, etc.).

In addition to the aforementioned causes, the literacy level in villages and rural areas are quite low. Many of the farmers and laborers from rural India are uneducated. As a result, many don’t know how medication can help them get better and how important it is to take medication every day to keep chronic conditions like hypertension and diabetes in control. In urban areas, all income classes are more educated and are given awareness more frequently about healthcare when compared to individuals in rural areas. So, they tend to use medication and other healthcare facilities more frequently. Accessibility is not a huge issue in cities but this creates competition among providers and results in high costs which turns into a problem for low and average income communities of the urban population.

Usually, regular medications like anti-diabetics, anti-hypertensives, common antibiotics, analgesics, vitamins are available throughout the country except in some deeply located tribal areas. Medications which are used for some cancer chemotherapies, auto-immune diseases, and some orphan drugs are not widely available. People have to go to highly rated hospitals in developed metropolitan cities to get these medications, and I believe this scenario is the same anywhere in the world. This kind of accessibility shouldn’t affect any patient or healthcare provider unless there is any medical emergency. And thanks to the continuous efforts of the Government of India, India is improving the accessibility of medication. Recently, various health benefit schemes were implemented like free supply of in-patient medications in civil hospitals and sale of reasonably priced generic medications in rural and urban communities.

It is a well-established fact that India is a potential supplier of medications to many countries in the world. India is a manufacturing and research hub for many reputed pharmaceutical companies. However, this often leads to pharmaceutical companies who are exporting their products in large quantities rather than supplying them domestically. These medications range from certain medications for chronic diseases like diabetes drugs to life saving medical devices like the Epi-Pen. These pharmaceutical companies more interested in profit are preventing the Indian population from getting the best medications.

With the lack of proper medications, healthcare professionals cannot take the proper steps in patient care that they could actually do if they had adequate access to medications. So, it is vital to educate people of India, especially the rural population, while simultaneously framing and implementing some regulations and limits on the export of medications by pharmaceutical companies in order to improve healthcare in India.

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.

The Future of HIV: Novel Treatment Options & A Possible Cure

As the medical community and those it serves welcomed in a new year, it brought with it the hope of scientific advancements that will alter the course of certain disease states. These advancements include the use of stem cells to treat to treat macular degeneration, novel microscopic techniques to capture images of the brain, the continued observed effectiveness of the experimental Ebola vaccine, and countless other interventions aimed at creating a healthier global society. Included in these optimisms for 2019 is the possibility for novel treatment options and a possible cure for one of the world’s leading causes of death, HIV. The stories of Timothy Brown – the only individual ever to be cured of HIV, the Mississippi baby and Clark Hawley – both having an extended period of time with undetectable HIV viral load with an interruption of Antiretroviral Therapy (ART), and the Boston patients/Mayo Clinic patient – all three having undetectable HIV viral loads for an extended period of time after a stem cell transplant, have brought much sanguinity to health care professionals and patients alike. However, these exciting results have been unable to be replicated in the majority of the population suffering from HIV and remain unique in their respective occurrences. Although ART has been vital to the HIV community in terms of longevity and quality life, there are still certain populations that are seeking other mechanisms to treat this infectious disease – and, of course, always coveting the idea of a cure. The following is a brief glimpse at the vast pipeline that awaits 2019 and the anticipations of the global healthcare community.  

Combination Approaches

  1. The AIDS Clinical Trial Group (ACTG) is currently exploring the option of combining vorinostat, a HDAC inhibitor along with tamoxifen, which is an FDA approved medication the treatment of breast cancer for postmenopausal women. Utilizing this approach is thought to prevent the reactivation of HIV in CD4+ cells that are latent in addition to increasing the latency-reversal effect of vorinostat through tamoxifen.
  2. Researchers from the USA, France, Germany, Italy, Spain, Switzerland, and the UK are collaborating for a trial testing the combination of two HIV vaccine candidates alongside a monoclonal antibody called vedolizumab. This method of treatment is thought to target a certain protein in the body, α4β7 integrin, that plays a role in transmission of HIV into CD4+ cells. In a macaque model, this combination has shown the control of SIV (HIV but in simians) after discontinuing ART.
  3. At the University of Minnesota, researchers are testing infusions of natural killer (NK) cells with the administration of cytokine interleukin-2 (IL-2). The researchers are hoping to add to the evidence of NK cells being able to exhaust HIV reservoirs and to control virus replication.
  4. In a version of the “kick & kill” method of curing HIV, researchers in Oxford and Barcelona are using a medication to active the latent HIV reservoir while boosting the immune response 1000 times stronger than the usual to rid the body of the virus. Preliminary results showed that 5/15 patients had undetectable viral loads for seven months without ART.

Immunotherapy Approaches

  1. Immunocore, a company founded in Oxford with heavy investment by Bill Gates, has designed T cell receptors that seek out and bind with the HIV virus. These receptors then instruct immune T cells to eliminate any HIV-infected cells, even when the levels happen to be extremely low. Since levels can be rather low in the reservoir of HIV virus that exists in an infected individual, this is a promising lead to completely remove this retrovirus from the body. This immunotherapy has shown to be effective in human tissue samples, but no results being tested in humans have been released.
  2. In France, a company known as InnaVirVax has established a vaccine, VAC-3S, that allows the body to stimulate a production of antibodies against the HIV protein 3S. This, in turn, causes T cells to attack the virus. This is considered a novel approach because it encourages the immune system to recover while equipping it with the tools to continue fighting off the virus. VAC-3S has completed Phase 2a trials, and is partnered with a DNA-based vaccine from FIT Biotech, a Finnish company, that both parties believe can lead to a functional cure.  
  3. In a recently initiated trial, IMPAACT 2008, held in the USA, Botswana, Brazil, and Zimbabwe, a broadly neutralizing antibody termed VRC01 is being investigated for its effectiveness in infants with HIV who are also started on ART within 12 weeks of birth. Although the study aims at establishing the safety profile for VRC01, it is also observing the difference in the HIV reservoir compared with only ART.

Novel Antiretroviral Agents

  1. The manufacturer, ABIVAX, believes it has developed a compound that may help the immune system recognize cells infected with HIV by allowing an increased presentation of HIV antigens on the cell’s service. This would lead to an augmented immune response to abolish these infected cells. This compound has been labelled ABX464 and targets the HIV protein Rev, which is responsible for the transcription of HIV RNA. Reductions of measured HIV DNA have been reported from 25% to 50% in eight of the fifteen patients participating in the study; however, no delay in viral load rebound was found when compared with placebo.
  2. Gilead has created a novel mechanism of targeting the HIV virus through the capsid inhibitors class. Capsids are involved in protecting HIV RNA and related proteins, and capsids also breaks down to release the viral contents into CD4 cells which enable reverse transcription to take place. The novel agent by Gilead, GS-CA1, blocks both the assembly and disassembly of capsids that create non-infectious and defective viruses.

Gene Therapy

  1. Chimeric antigen receptor (CAR) T therapy has been re-initiated in the first cure related clinical trial of this approach in people living with HIV who are on ART. CAR T cell therapy involves the modification of an individual’s T cells that can target antigens of interest. The specific cells modified by the initiative in China, called VC-CAR-T cells, have been modified to target HIV gp120. These modified cells were able to induce the destruction of HIV-infected cells, including latently infected cells exposed to latency-reversing agents, in the laboratory setting.  
  2. With the knowledge of knowing that about 1% of the world’s population is immune to HIV due to a genetic mutation on the gene that encodes for CCR5, US-based Sangamo has begun to edit DNA to introduce the aforementioned mutation. The CCR5 protein is attached to the surface of CD4 cells that allows HIV to enter and infect the cell; with the mutation, it would be impossible for HIV to enter cells. This company extracts patient’s CD4 cells in order to use zinc finger nucleases to edit patient’s DNA to make them resistant to HIV.
  3. Although a highly controversial topic amid the recent publication of the use of CRISPER in twin daughters in China, scientists believe that this tool can lead to a cure for HIV as it is believed to be a much easier, faster, and effective approach than other gene-editing methods. However, the majority of the global health community is in agreement that years of laboratory research and ethical standards need to be established before human trials are properly started.

With the HIV virus adapting and mutating to evade treatments almost as rapidly as the world is producing novel approaches to treating this infectious disease, the drive for continued research and testing should be relentless. These aforementioned examples of novel treatments and possible cures display the creative and diverse thought processes the medical community has put forth to tackle one of the most stigmatized diseases on this earth. However, the ethics behind these trials need to be sound and forthcoming for all of humanity. The trials that occur need to ensure an assortment of demographics including individuals from both developed and developing nations – a subtle form of medical colonialism has no place in the global health community. In addition, trials that enroll patients who willingly accept the benefits and risks associated with the experimental therapy have the moral obligation to supply lifetime treatment if it happens to be effective. The researchers and medical professionals who monitor these participants need to take extreme caution in ART interruptions/discontinuations and certify that the patients realize what complications could transpire due to them. Finally, and most importantly, the interventions that show promise of novel ways to approach HIV or even a cure have to be accessible, affordable, and available to all humans who suffer from HIV. The health inequalities that plague this fragile planet have already been clearly highlighted in this ailment throughout history; the global health community is in debt to humanity for a cure for all when discovered.  

With the global health community’s commitment, the future of the HIV virus continues to transition from infectious disease to chronic disease. While the step that will advance the chronic disease to a cure is still thought to be unknown, the excitement behind the aforementioned gene editing therapy is substantial. The ability to safely, effectively and ethically modify human cells to prevent the entry of the virus into the immune system is certainly the most promising option recently and possibly from this disease’s initial appearance; although, health care professionals haven’t quite figured out how to combine these aspects yet. A cure or even functional cure may be years away, but the global health community needs to continue to accompany those inflicted by this chronic infectious disease to meet the hopes and expectations of alleviating the burdens of HIV.