Challenge 1: News Flash
The first part of this challenge was to identify the extent to which participants of the study have heard about different types of medicine in the media. For the first survey, I chose that I have recently heard about “Shortages in medicine availability” in the media. I would note at this time that asking people to fill out a new survey for every topic they have heard in the media recently may be more time consuming. Perhaps the survey can be formatted to include multiple topics simultaneously in the survey. The next question in the survey asks if the news in mind when asked about the first question was at all related to the COVID-19 pandemic. While I have heard much about shortages in medicine availability due to lack of natural products needed to make these medicines, the most recent references to medicine shortages has been COVID-19 vaccines. These shortages have occurred because the demand for the vaccine is greater than the supply, as the resources, manpower, and space needed to produce the vaccine has not been sufficient during this time. After answering some questions about medicine shortages and what media sources I learned this information from, I decided to take another survey on another medicine and public health issue in the media: clinical trial process and results.
Challenge 2: Price Hikes
In this challenge, we will research if there has been any changes to the price of the drugs selected, including past and current pricing, and any further relevant information. To identify information regarding medicine affordability, it is important to confirm you are using a reliable and reputable source. In order to do so, ensure the URL ends in .gov, .org, or .edu and identify the author or contact information for the website. I thought it was important that they include how to do conduct some preliminary research and found it very helpful as a reader new to the experiment. Having the directions was successful in telling the reader what to do which helped and this challenge is more insightful than the last.
To begin my research, I googled “clotrimazole australia” to gain more background knowledge on its usage and how to take it. It is an antifungal cream that is used to treat a multitude of common fungal (yeast) skin infections including tinea (ringworms), athlete’s foot, vaginal thrush, and nappy rash. Clotrimazole is a topical medicine with a shelf life of three years and belongs to the Schedule 2 (Pharmacy Medicine) class, meaning you do not need to have a prescription for this medication. With that in mind, I began to research price hikes for clotrimazole. The first link was to the TGA regarding the scheduling application for vaginal application of clotrimazole, as it has been used for this application in the U.S. and U.K., and requires an update on the label regarding more situations in which you should contact your doctor. I found that the schedule history for clotrimazole dates all the way back to August of 1977. Clotrimazole was first made available to the Australian public as a Schedule 2 topical antifungal treatment in 1991 and has been used as an unscheduled dermal tinea pedis medicine since 2005. While this did include some relevant information regarding clotrimazole in general, I decided to continue going through the search results for more generalized information. In the third link, I found information regarding a court case on that detailed different companies’ ownership of Clotrimazole, where I discovered that Actavis Pharma, Inc. (page 19) is responsible for the manufacturing, promotion, and distribution of several drugs, one of which is Clotrimazole, all over the U.S. The pharmaceutical industry is heavily dependent on raw materials, or active pharmaceutical ingredients (APIs), which have risen in price 15-20% and upwards of 50% for some. 50 to 60 percent of the world’s APIs are from China, whose recent crackdown on pollution has led to the closure of several industrial plants, many of which include API manufacturers. Due to its versatility in anti-fungal medicines and treatments and the reduction of API manufacturing plants, the price of Clotrimazole rose from Rs 1400 per kg to Rs 2400 per kg in the span of six months in 2018. Between January and April of 2020, Clotrimazole was rated critical because its price rose by 24 to 38 percent. The rise in price of APIs and high government-set prices to manufacture drugs has created concerns for the future of some drugs on the market.
Challenge 3: Circle of Life
As this was the first drug in this challenge, I was a little wary of how to go about researching the history of the drug. I thought the visual representation for cycloserine was very necessary, as the description was a little vague. To aid in my research, I copied down the different pieces of the flow chart below to make sure I did not miss any key points:
Trade Name: Trivagazole 3
Developed By: Bayer
Currently Owned By: Taro Pharmaceuticals USA Inc.
Changes in Ownership (who, when): initial owner 1972, FDA approval 2000
Price Hike (who, when, price):
After going to the second page, I realized I did not need to search for some of this information, as it was located in a database link already provided. I thought the input of this information was a little unnecessary because it was already available on the spreadsheet given. On the next page, I thought the directions for the search results could have been emphasized more. Perhaps the initial directions could be chopped down more, with an emphasis on finding the first owner. Instead of having two pages, the page could be more user friendly if it was listed in a similar format to how it is written above (trade name, developed by, etc.) and separated into two sections in which one states information that can be found in the database link and another for information that needs to be found by researching. Some users might think they have already done this research because the directions looked very similar to the first set of research directions in Challenge 1 or 2. I began with the keywords listed in Step 1 (“clotrimazole 2000”) but that did not yield anything related. Then, I tried to refine my search in Step 4 by using “clotrimazole first owner” but once again did not find much with that. I then searched for “clotrimazole history” and had success with the first link. I learned that it was first patented by Bayer in 1972 and sold in Germany under the name Canesten a year later.
Medicine: Dapsone
Challenge 1: News Flash (recent news)
Upon doing a quick google and some preliminary research about Dapsone, I discovered it works to decrease inflammation and bacteria growth. Commonly used as a topical antibiotic, it can treat acne for teenagers, rashes from herpetiformis and leprosy infections. While it does treat these fairly common dermatological issues, I read an article that discussed how Dapsone is being considered as a drug that could have repurposing benefits against COVID-19 patients with severe inflammation.
As an anti-inflammatory and immune system regulator, this drug would be really helpful in reducing the amount of hospitalizations due to respiratory and hyperinflammation issues as a result of COVID-19. This was really interesting to read about, as the article really went into depth about how hyperinflammation occurs in the body as a result of COVID and how Dapsone can serve as a safe and tried therapeutic.
Challenge 2: Price Hikes
I did a generic search for price hikes for Dapsone and the first link was from December 13th, 2019. The website looked quite reliable and was from a common news outlet in India. It described how The National Pharmaceutical Pricing Authority (NPPA) raised the price of multiple medicines, including Dapsone, by fifty percent. The NPPA currently states that Dapsone costs 0.34 Rs per unit. This has occurred due to sourcing of APIs or active pharmaceutical ingredients needed to create Dapsone. I realized that clotrimazole also had the same issue with funding the source of these now scarce APIs. According to a medication and general prescription website called Good Rx, the most common version of Dapsone ranged from $22.10 to $94.42. As of August 2019, it has been confirmed that the price of branded Dapsone gel is $650 to $670 and the price of generic Dapsone gel is $100 to $150.
Challenge 3: Circle of Life
After completing challenge 3 for clotrimazole, I had a better idea of how to go about researching Dapsone’s ownership rights and trading details. Using the information in the table provided, I quickly identified details when asked about who owned the rights to Dapsone, the trade name, and the year. Based on step 1, I began my search with ‘dapsone 2005’ which yielded a couple articles, the first on how dapsone can suppress superoxide coming from neutrophils. It states that Dapsone best works on neutrophil-rich infiltrates such as neutrophilic dermatoses. The second scientific article discussed Dapsone hypersensitivity syndrome. I then came across a series of questions asked to the Minister for Veteran Affairs discussing dapsone in relation to the Australian Defense Force. I learnt that Dapsone was first used against active malaria in Vietnam in September 1967 until February 1970. This made me think about the FDA approval date of July 7, 2005 and how long its initial use was for more than 23,000 people during this time. After changing my google search terms to include history and ownership, I found that Dapsone had been used in combination with Chlorproguanil in the drug Lapdap to treat the growing cases of malaria in Africa. However, it was pulled off the market by its owners, GlaxoSmithKline, because 10 to 25 percent of the African population had G6PD deficiency and dapsone causes hemolytic anemia in those with G6PD deficiency. Known for its successful treatment against acne, the Dapsone gel, Aczone, was created by QLT USA in the early 2000s. This was a 5 percent gel that is applied twice daily to prevent leprosy. In February 2016, the FDA approved a 7.5 percent gel that is applied once daily. While I was not able to find any previous owners, there was no indication that dapsone had been owned by any other pharmaceutical but that it was used and reproduced by the owners of LapDap until QLT developed dapsone gel. I found that the manufacturer of dapsone was Jacobus Pharmaceutical Co and the packagers included the following:
Allergan Inc.
A-S Medication Solutions LLC
Comprehensive Consultant Services Inc.
Gallipot
Jacobus Pharmaceutical Co.
Kaiser Foundation Hospital
Murfreesboro Pharmaceutical Nursing Supply
PD-Rx Pharmaceuticals Inc.
Physicians Total Care Inc.
Prepak Systems Inc.
Remedy Repack
Tolmar Inc.
At first, I thought I would find the original owner by researching these packagers in hopes of finding a transition or hand over of ownership. However, I decided this would probably not yield much of a result so I changed tactics and rephrased my google search. I came across an article that I had not read all the way through, as I had assumed the article was only going to discuss the chemical structure of dapsone following the brief introduction on dapsone’s history. However, after reading through the article again, I noticed it mentioned that they would not go into further depth about the history of dapsone because it was included in referred literature. I switched my key words again to ‘allergan own aczone’ and found a brief article on The Pharma Letter, a database for pharmaceutical and biotechnology industry news, discussing the trade deal between QLT and Allergan for the rights to Aczone for 150 million. The questions in RedCap were more directed towards a merger or an acquisition of one company by another. I would recommend that RedCap be adjusted to include an option for an acquisition of rights to a drug without the acquisition of the company as well. While this often happens for other drugs, that specific event did not occur for this drug and may be confusing or misleading for future participants.
Medicine: Entecavir
Challenge 1: News Flash
Entecavir is used by patients with Hepatitis B as well as for those with HIV/AIDS and HBV antiretroviral medication. Upon doing some preliminary research on entecavir, I learned the brand name was Baraclude and works as a nucleoside analog that lowers the amount of HVB in the body. Overall, I was not able to find much news on entecavir through my google and google scholar searches. However, I did find an article from April 2019 comparing TDF with entecavir and which one performed better. Up until now, it was assumed that tenofovir diproxil fumarate (TDF) worked better than entecavir because there were less Hepatitis B patients who had to get transplants and less mortalities. Seeing as the calculated rates for mortality were no longer lower in patients taking TDF, Young-Suk Lim, MD, PhD, and Min Jung Ko, PhD, both of the University of Ulsan College of Medicine in Seoul, stated they would retract the original article and replace it. This has raised attention and the need for additional research to be conducted, including a more expansive study on chronic Hepatitis B patients taking both drugs specifically focusing on which drug is more effective and the effects on long term users, such as drug resistance.
Challenge 2: Price Hikes
As an extension to recent news about entecavir, I was shocked to find that most of the news outlets from Challenge 1 were from websites such as the Economic Times in India and financial reports about the entecavir company. I was curious as to what the Economic Times had stated so I took a closer look at each website’s articles. In the first website, I learned that the USFDA gave the drug company Cipla approval to manufacture and distribute Entecavir tablets in December 2016. It also mentioned that Entecavir tablets are the generic version of Baraclude tablets, produced by Bristol-Myers Suibb. I found this interesting that a generic form of the Hepatitis B drug had only recently been given the go ahead to be accessible to the public. Baraclude and its generic versions had made 206 million in the US from October 2015 to October 2016. Prior to reading this information, I did not understand why they would want to make another generic version of Baraclude if all the versions were successful. It makes sense that they would want to create another generic version seeing as it is so profitable in treating patients with Hepatitis B. Another website on the Economic Times (India) discussed the driving up of prices in general by the government. According to the pharmacologist Andrew Hill of Liverpool University, entecavir costs $4 to produce a year and costs $36 per person annually to produce, including $20 a year for packaging and a profit margin of 50%. This further implies the problems of price hikes, especially when the purchase price significantly outweighs the production costs and differs greatly from country to country. After looking through some more articles on that page, I found an article discussing the same research that was conducted at Liverpool University on factors that raise drug prices, including the cost and availability of APIs as well as current patents on the drug. The US currently sells entecavir for 15,000 which pails in comparison to its actual manufacture and production price of 36 US dollars. This makes it the most expensive medication for patients with chronic Hepatitis B on the market worldwide. The research done at Liverpool University has come at a perfect time because entecavir’s patent expires in February 2015. This means it can now be produced at a significantly lower rate of 36 USD which in conjunction with mass vaccination, could lower the current death rate due to Hepatitis B of 686,000 per year. After researching the consumer price in the US, I wanted to know more about the price for an Australian consumer. Across all of the pharmacies websites, the PBS rate for Baraclude was $40.30 AUSD and the private prescription rate varied from $65.99 to $160.95. The conversion from 36 USD to AUSD was 46.50, so Australia’s entecavir price has not been hiked by the government and is in keeping with its production price. The PBS price for Entecavir-Apotex costs 40 AUSD and the private prescription price is 199.99 AUSD. I thought it was interesting to see that the price between Entecavir and Baraclude differed much in private prescription rates, seeing how it is such a competitive market.
Challenge 3: Circle of Life
As I did for the other medicines, I completed the first part of this challenge by clicking on the link to the spreadsheet and identified the key information on the applicant holder, trade name, and approval date by the FDA. All three strengths of Entecavir were owned by Bristol Myers Squibb. I found this interesting for two reasons: the first being that other medicines such as Aczone had different applicant holders for two different strengths of the drug, and the second is that there are three different strengths for this drug, which indicates it is very strong. Instead of beginning my research using [drug name] + [year of FDA approval] as I did for the past two medicines, I decided to begin conducting my research using ‘entecavir owner’. Immediately, it came up that Bristol-Myers Squibb was the original patent holder for Baraclude, but that this patent expired in 2015. Following a lawsuit between Bristol Myers Squibb and Teva Pharmaceuticals USA, Teva Pharmaceuticals was given FDA approval to produce the 0.5 and 1 mg tablets, as well as Hetero Labs and Aurobindo Pharma later on.
Medicine: Ivermectin
Challenge 1: News Flash
When I first searched for Ivermectin news, I was not expecting to find so many articles on its relation to COVID-19. Seeing as all of the headlines under this keyword included COVID, I became intrigued as to the realistic potential of it being used in a vaccine or treatment plan. The first link gave a very brief description of a recent statement that the World Health Organization (WHO) put out advising Ivermectin’s use against COVID-19 has not yet been determined due to sample sizes and limitations. The panel was looking for evidence that Ivermectin could help to lower the number of mortalities, ventilator users, and hospital admissions. As of now, they recommend Ivermectin does not be used outside of clinical trials until further research is conducted. The next source in my google search was from the Australian Government page affirming the need for further research and clinical trials to be conducted before it is appropriate to give to the public. A report from the European Medicines Agency showed advancement in this matter, concluding Ivermectin is not a viable option for COVID-19 patients in the EU because such high doses were needed to stop the replication of SARS-CoV-2, the virus causing COVID-19, and therefore not suggested as a prevention or treatment technique for COVID outside of clinical trials. Despite the lack of clinical trials and evidence to its efficacy against COVID (as seen in Challenge 1), the popularity of Ivermectin has been especially popular in Latin America. Every 8 out of 10 people had already taken Ivermectin by the time global health researchers had tried to conduct studies on its antiviral properties. The craze for Ivermectin began after Australian researchers discovered that high doses of Ivermectin stopped cell replication of the virus.
Challenge 2: Price Hikes
With this heavy interest in Ivermectin as a potential treatment against COVID, I began to think that the price may have gone up recently, as more Ivermectin would be needed to conduct all of these trials. According to the Times of India, the price of Ivermectin had doubled or tripled from March 2020 to April 2020. Before reading this article, I assumed that the price would be greater because there would be a shortage in the amount of Ivermectin available. However, while the shortage in the market in China rose the price of APIs 80-100% causing API prices to increase, sea and importing prices have also risen along with congestion at sea ports. An example of this demand contributing to rising API prices and importation is in Latin America. This past May, almost 350,000 doses of Ivermectin was distributed to residents in North Bolivia. In Peru, a university stated they would produce 30,000 doses and 20,000 bottles of Ivermectin sold on the black market were found by police.
Challenge 3: Circle of Life
At this point in the challenges, I feel that this initial process of finding information from the google spreadsheet provided should be streamlined and automated if possible so that the computer generates this information for the participants. This would eliminate time and switching back and forth between tabs of information, especially if the user is on a device other than a computer and cannot easily switch back and forth between tabs because the information is presented in different applications on their phone or tablet. After looking at the table to fill in the necessary information, I found that there were four types of Ivermectin listed, a 1% cream Soolantra patented and owned by Galderma Laboratories LP, a 0.5% lotion Sklice patented and owned by Arbor Pharmaceuticals LLC, and a 3 mg and 6 mg tablet Stromactin owned by Merck Sharp and Dohme Corp. I chose to focus on the 3mg tablet Stromactin because both the 3mg and 6mg tablet were owned by the same company and were not patented. A google search for ‘patent ivermectin’ yielded a resource from the World Health Organization explaining how Ivermectin was created and that Merck had given away an unlimited supply in an effort to get rid of river blindness to those that needed it, something that a company had never done before.
Medicine: Praziquantel
Challenge 1: News Flash
Before researching current news surrounding praziquantel, I wanted to get some background regarding this drug, as I did not recognize the name. I discovered that it is a tablet sold under the brand Biltricide and an anthelmintic, used to treat multiple parasitic worm infections in humans and animals. This is called schistosomiasis and is caused by a schistosoma or blood fluke (flatworm parasite). Following my preliminary search, I found a Medical News page with several articles on new studies surrounding praziquantel. The first study discussed the vulnerabilities of schistosomes, which infect almost 240 million people worldwide and kill 250,000 every year. Currently, praziquantel is the only drug on the market that can treat schistosomiasis but it is not fully successful in doing so because it does not kill the schistosomes in all stages of its life cycle. I was disappointed to hear that pharmaceutical companies have not been interested enough to do further research on the biology of schistosomes and manufacturing of potential drugs because there is no large monetary incentive. James J. Collins III, an associate professor in the department of pharmacology at UTSW stated “ ‘This is a very important disease that most people have never heard of. We need to invest and invigorate research on these parasites’ “. Many of the other articles discussed a similar idea about the importance of research on schistosomiasis and finding drugs like praziquantel that can be more effective in killing schistosomes at all stages of its life cycle.
Challenge 2: Price Hikes
According to a report by Adam Feuerstein, the CEO Martin Shrukeli of the pharmaceutical company Retrophin, whose business plan is to buy small-market drugs and resell them at a higher price, is trying to get the drug rights to praziquantel from Bayer. Bayer sells one course of treatment which is six to nine pills per day for $100. Shrukeli plans to raise this price to $100,000 for one treatment. While Bayer did not take the offer, they decided to raise the price due to his high interest in the drug by 3.5 times in 2015, bringing the price to around $350 per treatment.
Challenge 3: Circle of Life
After inputting the information from the google spreadsheet on the trade name, application holder, and FDA approval date for Praziquantel, I decided to not follow the listed steps in regards to how to research. This is because I found this step was tedious as it made you go through several search results that have not been helpful in finding the first owner of the medicine but rather general or background knowledge on the creators of the medicine. Instead, I chose to start with a google result that usually yields more of an answer of the first owner: ‘patent praziquantel’. I found in one of the top searches that praziquantel was patented in Germany in 1973 and patented in the US four years later. Following this, Bayer and Merck registered the patent in 38 countries. This was the only mentioned owner in my research and Bayer is not a subsidiary, therefore I can conclude with confidence that they were the initial and current owner of Praziquantel.
SCDL1991 Journal Project E$$ENTIAL MEDICINE$ SID 510356817
Survey Queue: https://redcap.sydney.edu.au/surveys/?sq=Ka49U58RJT
Medicines Selected: Clotrimazole Dapsone Entecavir Ivermectin Praziquantel
Medicine: Clotrimazole
Challenge 1: News Flash The first part of this challenge was to identify the extent to which participants of the study have heard about different types of medicine in the media. For the first survey, I chose that I have recently heard about “Shortages in medicine availability” in the media. I would note at this time that asking people to fill out a new survey for every topic they have heard in the media recently may be more time consuming. Perhaps the survey can be formatted to include multiple topics simultaneously in the survey. The next question in the survey asks if the news in mind when asked about the first question was at all related to the COVID-19 pandemic. While I have heard much about shortages in medicine availability due to lack of natural products needed to make these medicines, the most recent references to medicine shortages has been COVID-19 vaccines. These shortages have occurred because the demand for the vaccine is greater than the supply, as the resources, manpower, and space needed to produce the vaccine has not been sufficient during this time. After answering some questions about medicine shortages and what media sources I learned this information from, I decided to take another survey on another medicine and public health issue in the media: clinical trial process and results.
Challenge 2: Price Hikes In this challenge, we will research if there has been any changes to the price of the drugs selected, including past and current pricing, and any further relevant information. To identify information regarding medicine affordability, it is important to confirm you are using a reliable and reputable source. In order to do so, ensure the URL ends in .gov, .org, or .edu and identify the author or contact information for the website. I thought it was important that they include how to do conduct some preliminary research and found it very helpful as a reader new to the experiment. Having the directions was successful in telling the reader what to do which helped and this challenge is more insightful than the last.
To begin my research, I googled “clotrimazole australia” to gain more background knowledge on its usage and how to take it. It is an antifungal cream that is used to treat a multitude of common fungal (yeast) skin infections including tinea (ringworms), athlete’s foot, vaginal thrush, and nappy rash. Clotrimazole is a topical medicine with a shelf life of three years and belongs to the Schedule 2 (Pharmacy Medicine) class, meaning you do not need to have a prescription for this medication. With that in mind, I began to research price hikes for clotrimazole. The first link was to the TGA regarding the scheduling application for vaginal application of clotrimazole, as it has been used for this application in the U.S. and U.K., and requires an update on the label regarding more situations in which you should contact your doctor. I found that the schedule history for clotrimazole dates all the way back to August of 1977. Clotrimazole was first made available to the Australian public as a Schedule 2 topical antifungal treatment in 1991 and has been used as an unscheduled dermal tinea pedis medicine since 2005. While this did include some relevant information regarding clotrimazole in general, I decided to continue going through the search results for more generalized information. In the third link, I found information regarding a court case on that detailed different companies’ ownership of Clotrimazole, where I discovered that Actavis Pharma, Inc. (page 19) is responsible for the manufacturing, promotion, and distribution of several drugs, one of which is Clotrimazole, all over the U.S. The pharmaceutical industry is heavily dependent on raw materials, or active pharmaceutical ingredients (APIs), which have risen in price 15-20% and upwards of 50% for some. 50 to 60 percent of the world’s APIs are from China, whose recent crackdown on pollution has led to the closure of several industrial plants, many of which include API manufacturers. Due to its versatility in anti-fungal medicines and treatments and the reduction of API manufacturing plants, the price of Clotrimazole rose from Rs 1400 per kg to Rs 2400 per kg in the span of six months in 2018. Between January and April of 2020, Clotrimazole was rated critical because its price rose by 24 to 38 percent. The rise in price of APIs and high government-set prices to manufacture drugs has created concerns for the future of some drugs on the market.
Challenge 3: Circle of Life As this was the first drug in this challenge, I was a little wary of how to go about researching the history of the drug. I thought the visual representation for cycloserine was very necessary, as the description was a little vague. To aid in my research, I copied down the different pieces of the flow chart below to make sure I did not miss any key points:
Trade Name: Trivagazole 3 Developed By: Bayer Currently Owned By: Taro Pharmaceuticals USA Inc. Changes in Ownership (who, when): initial owner 1972, FDA approval 2000 Price Hike (who, when, price):
After going to the second page, I realized I did not need to search for some of this information, as it was located in a database link already provided. I thought the input of this information was a little unnecessary because it was already available on the spreadsheet given. On the next page, I thought the directions for the search results could have been emphasized more. Perhaps the initial directions could be chopped down more, with an emphasis on finding the first owner. Instead of having two pages, the page could be more user friendly if it was listed in a similar format to how it is written above (trade name, developed by, etc.) and separated into two sections in which one states information that can be found in the database link and another for information that needs to be found by researching. Some users might think they have already done this research because the directions looked very similar to the first set of research directions in Challenge 1 or 2. I began with the keywords listed in Step 1 (“clotrimazole 2000”) but that did not yield anything related. Then, I tried to refine my search in Step 4 by using “clotrimazole first owner” but once again did not find much with that. I then searched for “clotrimazole history” and had success with the first link. I learned that it was first patented by Bayer in 1972 and sold in Germany under the name Canesten a year later.
Medicine: Dapsone
Challenge 1: News Flash (recent news) Upon doing a quick google and some preliminary research about Dapsone, I discovered it works to decrease inflammation and bacteria growth. Commonly used as a topical antibiotic, it can treat acne for teenagers, rashes from herpetiformis and leprosy infections. While it does treat these fairly common dermatological issues, I read an article that discussed how Dapsone is being considered as a drug that could have repurposing benefits against COVID-19 patients with severe inflammation.
As an anti-inflammatory and immune system regulator, this drug would be really helpful in reducing the amount of hospitalizations due to respiratory and hyperinflammation issues as a result of COVID-19. This was really interesting to read about, as the article really went into depth about how hyperinflammation occurs in the body as a result of COVID and how Dapsone can serve as a safe and tried therapeutic.
Challenge 2: Price Hikes I did a generic search for price hikes for Dapsone and the first link was from December 13th, 2019. The website looked quite reliable and was from a common news outlet in India. It described how The National Pharmaceutical Pricing Authority (NPPA) raised the price of multiple medicines, including Dapsone, by fifty percent. The NPPA currently states that Dapsone costs 0.34 Rs per unit. This has occurred due to sourcing of APIs or active pharmaceutical ingredients needed to create Dapsone. I realized that clotrimazole also had the same issue with funding the source of these now scarce APIs. According to a medication and general prescription website called Good Rx, the most common version of Dapsone ranged from $22.10 to $94.42. As of August 2019, it has been confirmed that the price of branded Dapsone gel is $650 to $670 and the price of generic Dapsone gel is $100 to $150.
Challenge 3: Circle of Life After completing challenge 3 for clotrimazole, I had a better idea of how to go about researching Dapsone’s ownership rights and trading details. Using the information in the table provided, I quickly identified details when asked about who owned the rights to Dapsone, the trade name, and the year. Based on step 1, I began my search with ‘dapsone 2005’ which yielded a couple articles, the first on how dapsone can suppress superoxide coming from neutrophils. It states that Dapsone best works on neutrophil-rich infiltrates such as neutrophilic dermatoses. The second scientific article discussed Dapsone hypersensitivity syndrome. I then came across a series of questions asked to the Minister for Veteran Affairs discussing dapsone in relation to the Australian Defense Force. I learnt that Dapsone was first used against active malaria in Vietnam in September 1967 until February 1970. This made me think about the FDA approval date of July 7, 2005 and how long its initial use was for more than 23,000 people during this time. After changing my google search terms to include history and ownership, I found that Dapsone had been used in combination with Chlorproguanil in the drug Lapdap to treat the growing cases of malaria in Africa. However, it was pulled off the market by its owners, GlaxoSmithKline, because 10 to 25 percent of the African population had G6PD deficiency and dapsone causes hemolytic anemia in those with G6PD deficiency. Known for its successful treatment against acne, the Dapsone gel, Aczone, was created by QLT USA in the early 2000s. This was a 5 percent gel that is applied twice daily to prevent leprosy. In February 2016, the FDA approved a 7.5 percent gel that is applied once daily. While I was not able to find any previous owners, there was no indication that dapsone had been owned by any other pharmaceutical but that it was used and reproduced by the owners of LapDap until QLT developed dapsone gel. I found that the manufacturer of dapsone was Jacobus Pharmaceutical Co and the packagers included the following:
At first, I thought I would find the original owner by researching these packagers in hopes of finding a transition or hand over of ownership. However, I decided this would probably not yield much of a result so I changed tactics and rephrased my google search. I came across an article that I had not read all the way through, as I had assumed the article was only going to discuss the chemical structure of dapsone following the brief introduction on dapsone’s history. However, after reading through the article again, I noticed it mentioned that they would not go into further depth about the history of dapsone because it was included in referred literature. I switched my key words again to ‘allergan own aczone’ and found a brief article on The Pharma Letter, a database for pharmaceutical and biotechnology industry news, discussing the trade deal between QLT and Allergan for the rights to Aczone for 150 million. The questions in RedCap were more directed towards a merger or an acquisition of one company by another. I would recommend that RedCap be adjusted to include an option for an acquisition of rights to a drug without the acquisition of the company as well. While this often happens for other drugs, that specific event did not occur for this drug and may be confusing or misleading for future participants.
Medicine: Entecavir
Challenge 1: News Flash Entecavir is used by patients with Hepatitis B as well as for those with HIV/AIDS and HBV antiretroviral medication. Upon doing some preliminary research on entecavir, I learned the brand name was Baraclude and works as a nucleoside analog that lowers the amount of HVB in the body. Overall, I was not able to find much news on entecavir through my google and google scholar searches. However, I did find an article from April 2019 comparing TDF with entecavir and which one performed better. Up until now, it was assumed that tenofovir diproxil fumarate (TDF) worked better than entecavir because there were less Hepatitis B patients who had to get transplants and less mortalities. Seeing as the calculated rates for mortality were no longer lower in patients taking TDF, Young-Suk Lim, MD, PhD, and Min Jung Ko, PhD, both of the University of Ulsan College of Medicine in Seoul, stated they would retract the original article and replace it. This has raised attention and the need for additional research to be conducted, including a more expansive study on chronic Hepatitis B patients taking both drugs specifically focusing on which drug is more effective and the effects on long term users, such as drug resistance.
Challenge 2: Price Hikes As an extension to recent news about entecavir, I was shocked to find that most of the news outlets from Challenge 1 were from websites such as the Economic Times in India and financial reports about the entecavir company. I was curious as to what the Economic Times had stated so I took a closer look at each website’s articles. In the first website, I learned that the USFDA gave the drug company Cipla approval to manufacture and distribute Entecavir tablets in December 2016. It also mentioned that Entecavir tablets are the generic version of Baraclude tablets, produced by Bristol-Myers Suibb. I found this interesting that a generic form of the Hepatitis B drug had only recently been given the go ahead to be accessible to the public. Baraclude and its generic versions had made 206 million in the US from October 2015 to October 2016. Prior to reading this information, I did not understand why they would want to make another generic version of Baraclude if all the versions were successful. It makes sense that they would want to create another generic version seeing as it is so profitable in treating patients with Hepatitis B. Another website on the Economic Times (India) discussed the driving up of prices in general by the government. According to the pharmacologist Andrew Hill of Liverpool University, entecavir costs $4 to produce a year and costs $36 per person annually to produce, including $20 a year for packaging and a profit margin of 50%. This further implies the problems of price hikes, especially when the purchase price significantly outweighs the production costs and differs greatly from country to country. After looking through some more articles on that page, I found an article discussing the same research that was conducted at Liverpool University on factors that raise drug prices, including the cost and availability of APIs as well as current patents on the drug. The US currently sells entecavir for 15,000 which pails in comparison to its actual manufacture and production price of 36 US dollars. This makes it the most expensive medication for patients with chronic Hepatitis B on the market worldwide. The research done at Liverpool University has come at a perfect time because entecavir’s patent expires in February 2015. This means it can now be produced at a significantly lower rate of 36 USD which in conjunction with mass vaccination, could lower the current death rate due to Hepatitis B of 686,000 per year. After researching the consumer price in the US, I wanted to know more about the price for an Australian consumer. Across all of the pharmacies websites, the PBS rate for Baraclude was $40.30 AUSD and the private prescription rate varied from $65.99 to $160.95. The conversion from 36 USD to AUSD was 46.50, so Australia’s entecavir price has not been hiked by the government and is in keeping with its production price. The PBS price for Entecavir-Apotex costs 40 AUSD and the private prescription price is 199.99 AUSD. I thought it was interesting to see that the price between Entecavir and Baraclude differed much in private prescription rates, seeing how it is such a competitive market.
Challenge 3: Circle of Life As I did for the other medicines, I completed the first part of this challenge by clicking on the link to the spreadsheet and identified the key information on the applicant holder, trade name, and approval date by the FDA. All three strengths of Entecavir were owned by Bristol Myers Squibb. I found this interesting for two reasons: the first being that other medicines such as Aczone had different applicant holders for two different strengths of the drug, and the second is that there are three different strengths for this drug, which indicates it is very strong. Instead of beginning my research using [drug name] + [year of FDA approval] as I did for the past two medicines, I decided to begin conducting my research using ‘entecavir owner’. Immediately, it came up that Bristol-Myers Squibb was the original patent holder for Baraclude, but that this patent expired in 2015. Following a lawsuit between Bristol Myers Squibb and Teva Pharmaceuticals USA, Teva Pharmaceuticals was given FDA approval to produce the 0.5 and 1 mg tablets, as well as Hetero Labs and Aurobindo Pharma later on.
Medicine: Ivermectin
Challenge 1: News Flash When I first searched for Ivermectin news, I was not expecting to find so many articles on its relation to COVID-19. Seeing as all of the headlines under this keyword included COVID, I became intrigued as to the realistic potential of it being used in a vaccine or treatment plan. The first link gave a very brief description of a recent statement that the World Health Organization (WHO) put out advising Ivermectin’s use against COVID-19 has not yet been determined due to sample sizes and limitations. The panel was looking for evidence that Ivermectin could help to lower the number of mortalities, ventilator users, and hospital admissions. As of now, they recommend Ivermectin does not be used outside of clinical trials until further research is conducted. The next source in my google search was from the Australian Government page affirming the need for further research and clinical trials to be conducted before it is appropriate to give to the public. A report from the European Medicines Agency showed advancement in this matter, concluding Ivermectin is not a viable option for COVID-19 patients in the EU because such high doses were needed to stop the replication of SARS-CoV-2, the virus causing COVID-19, and therefore not suggested as a prevention or treatment technique for COVID outside of clinical trials. Despite the lack of clinical trials and evidence to its efficacy against COVID (as seen in Challenge 1), the popularity of Ivermectin has been especially popular in Latin America. Every 8 out of 10 people had already taken Ivermectin by the time global health researchers had tried to conduct studies on its antiviral properties. The craze for Ivermectin began after Australian researchers discovered that high doses of Ivermectin stopped cell replication of the virus.
Challenge 2: Price Hikes With this heavy interest in Ivermectin as a potential treatment against COVID, I began to think that the price may have gone up recently, as more Ivermectin would be needed to conduct all of these trials. According to the Times of India, the price of Ivermectin had doubled or tripled from March 2020 to April 2020. Before reading this article, I assumed that the price would be greater because there would be a shortage in the amount of Ivermectin available. However, while the shortage in the market in China rose the price of APIs 80-100% causing API prices to increase, sea and importing prices have also risen along with congestion at sea ports. An example of this demand contributing to rising API prices and importation is in Latin America. This past May, almost 350,000 doses of Ivermectin was distributed to residents in North Bolivia. In Peru, a university stated they would produce 30,000 doses and 20,000 bottles of Ivermectin sold on the black market were found by police.
Challenge 3: Circle of Life At this point in the challenges, I feel that this initial process of finding information from the google spreadsheet provided should be streamlined and automated if possible so that the computer generates this information for the participants. This would eliminate time and switching back and forth between tabs of information, especially if the user is on a device other than a computer and cannot easily switch back and forth between tabs because the information is presented in different applications on their phone or tablet. After looking at the table to fill in the necessary information, I found that there were four types of Ivermectin listed, a 1% cream Soolantra patented and owned by Galderma Laboratories LP, a 0.5% lotion Sklice patented and owned by Arbor Pharmaceuticals LLC, and a 3 mg and 6 mg tablet Stromactin owned by Merck Sharp and Dohme Corp. I chose to focus on the 3mg tablet Stromactin because both the 3mg and 6mg tablet were owned by the same company and were not patented. A google search for ‘patent ivermectin’ yielded a resource from the World Health Organization explaining how Ivermectin was created and that Merck had given away an unlimited supply in an effort to get rid of river blindness to those that needed it, something that a company had never done before.
Medicine: Praziquantel
Challenge 1: News Flash Before researching current news surrounding praziquantel, I wanted to get some background regarding this drug, as I did not recognize the name. I discovered that it is a tablet sold under the brand Biltricide and an anthelmintic, used to treat multiple parasitic worm infections in humans and animals. This is called schistosomiasis and is caused by a schistosoma or blood fluke (flatworm parasite). Following my preliminary search, I found a Medical News page with several articles on new studies surrounding praziquantel. The first study discussed the vulnerabilities of schistosomes, which infect almost 240 million people worldwide and kill 250,000 every year. Currently, praziquantel is the only drug on the market that can treat schistosomiasis but it is not fully successful in doing so because it does not kill the schistosomes in all stages of its life cycle. I was disappointed to hear that pharmaceutical companies have not been interested enough to do further research on the biology of schistosomes and manufacturing of potential drugs because there is no large monetary incentive. James J. Collins III, an associate professor in the department of pharmacology at UTSW stated “ ‘This is a very important disease that most people have never heard of. We need to invest and invigorate research on these parasites’ “. Many of the other articles discussed a similar idea about the importance of research on schistosomiasis and finding drugs like praziquantel that can be more effective in killing schistosomes at all stages of its life cycle.
Challenge 2: Price Hikes According to a report by Adam Feuerstein, the CEO Martin Shrukeli of the pharmaceutical company Retrophin, whose business plan is to buy small-market drugs and resell them at a higher price, is trying to get the drug rights to praziquantel from Bayer. Bayer sells one course of treatment which is six to nine pills per day for $100. Shrukeli plans to raise this price to $100,000 for one treatment. While Bayer did not take the offer, they decided to raise the price due to his high interest in the drug by 3.5 times in 2015, bringing the price to around $350 per treatment.
Challenge 3: Circle of Life After inputting the information from the google spreadsheet on the trade name, application holder, and FDA approval date for Praziquantel, I decided to not follow the listed steps in regards to how to research. This is because I found this step was tedious as it made you go through several search results that have not been helpful in finding the first owner of the medicine but rather general or background knowledge on the creators of the medicine. Instead, I chose to start with a google result that usually yields more of an answer of the first owner: ‘patent praziquantel’. I found in one of the top searches that praziquantel was patented in Germany in 1973 and patented in the US four years later. Following this, Bayer and Merck registered the patent in 38 countries. This was the only mentioned owner in my research and Bayer is not a subsidiary, therefore I can conclude with confidence that they were the initial and current owner of Praziquantel.