Access to Experimental Drugs

Experimental drugs can be a lifeline for those with conditions for which conventional treatments are not working or readily available. At the same time, doctors and patients want to have confidence that they are making safe and informed choices when requesting the use of drugs that have not have fully completed the clinical trial process.  With many doctors turning to experimental treatments for COVID-19 patients, this topic has recently gained renewed attention. Two processes in particular: compassionate use and Right to Try, give patients with serious or terminal conditions the ability to gain access to treatments which have not received FDA approval. These treatments can be potentially lifesaving for those whom conventional treatment is either unavailable or not working.

Compassionate use, formally known as Expanded Access, allows patients access to experimental treatments with approval from their doctor, the FDA, and an Institutional Review Board (IRB). The patient must meet several criteria, including having a serious disease or condition for which no comparable satisfactory treatment is available and being unable to enroll in clinical trials for the drug. If patients decide to pursue compassionate use, they must first speak to their physician, who then files a request to both the FDA and IRB. Eligibility is granted by the FDA if the agency determines that both (1) the benefits of using the experimental treatment outweigh any risks and (2) that its use will not jeopardize ongoing clinical trials. The FDA must respond to such a request within thirty days, and approval has historically been granted in 99% of cases. Secondly, the use must be approved by a registered IRB. Only once both of these steps are complete is the patient allowed access to the drug.

In May 2018 Congress passed the Right to Try Act, establishing a second process for patients to gain access to experimental treatments. Under Right to Try, patients with life-threatening conditions no longer need the approval of the FDA and IRBs to gain access to certain experimental drugs. Those with a terminal illness can submit a request directly to the manufacturer of an experimental treatment with the consent of their doctor. They may then obtain the treatment if the manufacturer approves. Similar to with compassionate use, patients using the Right to Try process must have exhausted all available conventional treatments and be unable to participate in clinical trails involving the experimental drug. The medication must also have completed Phase 1 clinical trials, an additional requirement not present in the compassionate use process. Right to Try has proven controversial in the scientific community since its conception. Proponents claim it cuts red tape patients for terminally ill patients in obtaining treatment, but critics point to the lack of reporting requirements and say that Right to Try removes safeguards in the compassionate use process that ensure patient safety.

While compassionate use and Right to Try have different processes, the programs share several key limitations. Importantly, manufacturers have no obligation to provide experimental drugs under either process, and the FDA has no power to compel companies to do so. Many manufacturers are reluctant to provide patients access to experimental drugs due to concerns that adverse reactions could lead to negative publicity or interfere with the FDA approval process.  Additionally, insurance companies are under no obligation to cover experimental treatments. The fact that many patients must pay out-of-pocket for experimental treatments has led to a stratified system where low-income patients are unable to obtain experimental drugs.

Despite these constraints, both compassionate use and Right to Try continued to be utilized by doctors and patients across the country. Many individuals with severe or terminal illness can’t afford to wait the seven to twelve years it takes for drugs to be approved by the FDA. Through compassionate use and Right to Try, these patients with few options left get a renewed chance.

Clinical Trials 101

Any time a new drug appears on the market, the final product is a result of years of research and testing. The time from conception to FDA approval for medications takes 12 years on average. An important and time-consuming aspect of this process are clinical trials. By testing a drug on gradually increasing numbers of patients and volunteers, researchers are able verify that it is both safe and effective in treating the disease or condition. Only when the first three steps of this process are complete can the drug be approved and commercially distributed.

Phase 1 is the shortest of the three phases and involves the smallest sample size. This phase is the first time a new drug is tested on humans and establishes the product’s safety. During Phase 1, the drug is given to 20 to 50 volunteers. Generally, this process takes several months. By examining subjects over this period, researchers are able to determine the appropriate dosage, observe side effects, and glean limited information about the drug’s effectiveness. These data are taken into consideration as researchers plan for Phase 2, which approximately 70% of drugs move onto.

Phase 2 gives researchers a clearer picture of a drug’s efficacy and safety. With preliminary safety data available, testing can be expanded to groups of up to several hundred patients. While these samples typically aren’t large enough to fully test a drug’s effectiveness, the results provide further insight into whether it is safe. Phase 2 trials last several months to two years. They are critical in winnowing out unsafe or unsuccessful drugs, with only approximately 33% of drugs proceeding to Phase 3.

The longest and most complex step of clinical trials is Phase 3, which involves 30 to 300 patients and takes 1 to 4 years. Phase 3 answers the most critical question for any drug: whether it provides the beneficial treatment it was designed to. Researchers test this by randomizing the study’s participants. Half of patients receive the experimental drug, while the other half are given a placebo. Studies are usually double-blind, which means neither the participant nor the researchers know who is in which group. Results from the two groups are then compared to determine the effectiveness of the drug. Phase 3 also provides additional safety data by sometimes revealing side effects that went undetected in smaller sample groups. Approximately 25 to 30% of drugs complete this phase and are ready for FDA approval.

Once drugs are FDA approved and commercially available, further testing continues in Phase 4 clinical trials. Although the drug has already been approved, Phase 4 allows for analysis of any long-term effects. Additionally, Phase 4 allows for more organic testing among groups that may not have been studied due to the controlled nature of previous phases, such as those simultaneously taking other drugs. Sometimes, drugs are banned from use by the FDA after harmful side effects emerge during Phase 4.

Clinical trials are a time-consuming, expensive, and selective process. Drugs that make it through and are FDA approved have an average cost of $41,117 per patient just for clinical trials. The federal government has created a database that is home to information about both privately and publicly funded clinical studies around the world. However, clinical trials remain the most comprehensive method available to ensure that every drug marketed in the U.S. is both safe and effective. Doctors and patients can have confidence knowing the drugs they prescribe, and use, have been put to this test and passed.

drug discovery timeline graphic

Introduction to Artificial Intelligence and Healthcare

The healthcare industry generates a lot of data. X-rays, pathology slides, patient vitals, clinical trial information; we have mountains of information accessible at the touch of a button. But it’s costly and time-inefficient for humans to manually pour over it. So what do we do with all of this data?

The field of intelligence (AI) allows not only to let us analyze all our data, but to find subtle and complex patterns in them. Machine learning algorithms are particularly responsible for these advancements. Engineers have developed software that’s able to look at a dataset, find relationships between a bunch of variables, and then make mathematical models that we can use to predict behaviors in the future or analyze other sources of data: images, patient records, etc.

What does that mean in the real world? Computer scientists can make systems that can analyze an image and detect a disease better than humans can. They can make programs that are able to predict the notoriously unpredictable process of how proteins fold, or even make drugs which are currently in human trials. Let’s learn a little more about how machine learning works, and see some of the current applications.

How machine learning systems work

Machine learning systems are complex algorithms. Algorithms are methods of “treating” data: a computer receives an input, some sort of data. The computer recognizes that data and sorts it. For example, let’s say I have a program that can tell me if the color of an animal I’m thinking about makes sense. if I type in the phrase “blue horse,” there might be something in the code that recognizes the word “blue” and the word “horse.” The code then might have some information about the colors a horse can be, and would have an instruction to compare “blue” with “horse.” If “blue” isn’t in the “horse” database, then the computer would have an instruction to tell me “No, horses can’t be blue.” To make it simple, algorithms are sets of instructions that do something with information we give it.

AI Flow Chart

A simple algorithm for calculating interest. Courtesy of Edraw.

They get way more complex than that example. Specific algorithms can take ridiculous amounts of data and look for statistical relationships between them. Machine learning systems are able to make new models by using what are called learning algorithms. There are a bunch of different types, but the most conceptually simple ones involve supervised learning. These learning algorithms are exposed to a “training set” of data with a bunch of examples with known “right answers” — for example, a bunch of CT scan images from patients whom we know have cancer or not. The algorithm “doesn’t know” which patients have the disease. It keeps changing the instructions inside of its algorithm to try to — if the computer sees a white spot in a patient’s liver, it says yes, but this turned out to be wrong, so the next time the computer doesn’t care about that spot when saying yes or no.

Do this a bunch of times, and eventually the algorithm learns what data points lead to the correct output: the machine learns. Over time, these algorithms get very accurate, and we can use them for specific applications.

Radiology and imaging

Image analysis is a very natural application of this sort of software. The cancer example above isn’t science fiction: Google’s already developed a system that’s able to detect breast cancer. A very recent study published information about a deep learning model that’s able to diagnose forms of common hip arthritis at an accuracy rivaling radiologists’ analysis.

But there are concerns about the current state of radiology AI and bringing these technologies to the clinic. Analyzing images is a very complex process, critics argue, and we don’t always know how these machine learning systems actually work. Although applications are rapidly developing, it’s clear that radiologists are still very necessary.

Breast Cancer Image

A picture of an image where an AI system found cancer in a human breast. Courtesy of Northwestern University via The New York Times.

Drug discovery

UK-based startup Exscientia became the first company to develop a small-molecule drug entirely designed by artificial intelligence. Small-molecule drugs are tiny chemicals that generally “stick” to proteins of interest. It is very hard to know what sort of molecules will stick and treat a disease and which ones won’t. The scientists at Exscientia use a learning algorithm that takes data from human-run tests to optimize the structure of the chemical they’re making, reducing the amount of time it takes to get a working drug. The compound, titled DSP-181 and targeted toward treating obsessive-compulsive disorder, is set to enter clinical trials in Japan soon.

Point-of-care solutions

AI doesn’t just help us make drugs; it can help us deliver them, too. Electronic health record systems are growing more and more. Nurses say that bureaucratic work cuts their time spent with patients by about 25 percent. Doctors report that less than half of their patients are what they’d describe as “highly engaged” in their course of care. Engineers are already developing systems that can not only manage data, but use electronic information to make predictions about how patients might comply with certain treatments.

From point-of-care solutions and radiology to drug discovery and beyond, it’s clear that artificial intelligence will play an increasingly large role in analyzing healthcare data in the future in ways both known and unknown to us now. New applications of machine learning systems are rapidly developing as engineers aim to create new machine learning algorithms that can analyze and find complex data. Used in tandem with the expertise of doctors, radiologists, and other healthcare professionals, these algorithm-based technologies are already modernizing our healthcare system and have the potential to improve public health on an even larger scale in the future.

Small Business Administration and Coronavirus Assistance

With the COVID-19 outbreak sweeping the country, and over 75% of Americans currently under shelter-in place orders, small businesses face a prolonged period of economic uncertainty. To help these businesses survive the coming months, Congress included several relief measures in the Coronavirus Aid, Relief, and Economic Security Act (CARES) Act, passed on March 27. The CARES Act provides wide-ranging relief for small businesses affected by the crisis, including hundreds of billions of dollars of loans and grants designed to ensure businesses keep employees on their payrolls and have the necessary cash to weather the crisis. Below, we highlight these resources and which businesses stand to benefit:

Paycheck Protection Program
Most businesses with 500 or fewer employees can apply to receive loans from the Paycheck Protection Program, which is designed to prevent widespread layoffs by small businesses. Businesses receiving this assistance can receive up to $10 million loans from banks and lenders backed by the federal government. If all employees are kept on the payroll for the next eight weeks, the principle on the loans will be forgiven and businesses will only be on the hook for interest. One caveat is that small businesses where venture capital firms have more than 50% equity are disqualified from participation. Many startups could be left out of the program under these rules.

Economic Injury Disaster Loans and Loan Advance
For small businesses who need additional assistance staying afloat, Economic Injury Disaster Loans and Loan Advances are available. Businesses can receive loans up to $2 million and $100,000 in loan advances. The advance does not have to be repaid and can serve as a lifeline for businesses currently experiencing a loss of revenue. Generally, businesses must be smaller than 500 employees to qualify. Additional requirements and the application page can be found here.

SBA Debt Relief
The SBA’s Debt Relief program can provide relief for businesses with existing loans or seeking to take out new loans. Under the new Debt Relief program, the SBA will pay the interest and principle of current 7(a) loans for a period of six months and new 7(a) loans issued until September 27, 2020.  7(a) loans are the SBA’s primary existing lending program for small business and can be issued in amounts of up to $10 million.

SBA Express Bridge Loans
Lenders already receiving loans from the Express Bridge Pilot program can now receive up to $25,000 in additional loans with additional paperwork. These funds can be accessed with fast turnaround and used while businesses apply for additional relief.

More information can be found at: https://www.sba.gov/page/coronavirus-covid-19-small-business-guidance-loan-resources

Finding Emory Innovations to Build Your Company’s Product Pipeline

Emory has approximately 600 technologies available to license at any given time. In particular, Emory offers a variety of live science resources such as therapeutics, diagnostics, and research tools that are marketed by Emory OTT.  

However, finding new technologies available at a university can be time-consuming and potentially frustrating for startups and established companies alike. Below are simple ways to find and remain up-to-date with technologies coming from Emory University.

  1. Subscribe to TechFeed to receive email notifications about products: TechFeed is a notification system where users can sign up to receive emails about recently added technologies. It can be individually customized to get notifications based on what products you’re interested in and how frequently you want to be notified. 

  2. Use our Technology Listings page: To get an improved searching experience with more accurate results, use our Google-powered search option. Through this, you can find non-confidential summaries of available technologies. Alternatively, if you’re looking for something around a specific indication or topic, click on Keywords in our word cloud and Technology Categories to get a list of these technologies.

  3. Visit our Featured Innovations page: Using these articlesable technologies.

  4. Contact our knowledgeable Marketing Associate, Quentin Thomas: Reach out to Quentin via email to request a hand-picked selection of technologies related to your needs and areas of interest. Quentin also encourages interested parties to set up a face-to-face conversation with him so he can guide the path from there. 

  5. Subscribe to our RSS feed and follow us on Twitter @Emory OTT: By doing this, you can stay up-to-date with all of our new technologies as soon as they’re listed on the website.

Additionally, to find a one-stop shop to find technologies from Emory as well as universities worldwide, there are a number of third-party listing services available to search free of charge, including the Association of University Technology Managers (AUTM) Innovation Market (AIM).

Our goal as technology matchmakers is to simplify the process for industry colleagues to find our technologies. If you have any suggestions on how we can improve this process, please contact us.

What is Diabetic Nephropathy?

Diabetic nephropathy, or diabetic kidney disease, is a common condition associated with Type I or Type II diabetes. It is estimated that about 20-40% of diabetic patients develop some form of kidney disease. If undetected, diabetic nephropathy can be a debilitating and dangerous disease, which is why people with diagnosed diabetes have to be frequently monitored for kidney function.

The main role of the kidneys is to filter the blood and remove waste and harmful products, while maintaining proteins, water and other useful substances. More specifically, kidneys contain small blood vessels called glomeruli that are responsible for filtering a large volume of blood every day. There are two kidneys in the human body, working together in a complementary manner. However, if one kidney stops working, the glomeruli in the other kidney start filtering more blood to compensate for the loss of function. This is why people can live without issues if they have at least one functioning kidney.

In unregulated diabetes, blood sugar levels are elevated, which slowly damages the glomeruli. Furthermore, many diabetics also have high blood pressure, which also stresses kidney function over time. When glomeruli stop functioning properly, protein starts leaking in the urine and eventually harmful waste may stay in the bloodstream, causing severe problems.

Thankfully, diabetic nephropathy can be prevented in most cases by maintaining regulated blood sugar levels. However, even if a patient reaches the early stages of nephropathy, blood sugar regulation can slow down the progression of kidney disease. If left untreated, both kidneys may fail, in which case interventional treatments such as dialysis or even a kidney transplant may be necessary. Transplants can come from compatible organ donors that have fully functional kidneys and a compatible blood type to the recipient. Frequently, transplants come from living donors, which often are family members wanting to help their loved ones.

More resources on diabetic nephropathy

  1. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/diabetic-kidney-disease

  2. National Kidney Foundation. https://www.kidney.org/atoz/content/Diabetes-and-Kidney-Disease-Stages1-4

  3. American Heart Association. https://www.heart.org/en/health-topics/diabetes/why-diabetes-matters/kidney-disease–diabetes

— Vicky Kanta

Announcements

Two important updates 

  1.  All staff in the Office of Technology Transfer are now working remotely, telecommuting. The office is still open for business and fully functional. Please reach out and we are ready to help. To find a complete staff listing go to our staff page on our website.

  2. Any new request for an Unfunded Research Contract should be sent to ott-mta [at] emory [dot] edu. Please fill out the appropriate questionnaire from our website to reduce processing time. The review of the agreement can not start until this information is submitted.

  3. Submitting a disclosure form can now be done on-line with our new tool called IdeaGate. Please go to the IdeaGate website to submit.

  4. The blog posts will slow down during this work from home period.

The Promise of CRISPR-Cas

Our bodies are made up of various cell groups that can do different things depending on the combinations of proteins they contain. Proteins can do wonderfully complex things, from acting as oxygen sensors to molecular motors. All of the information for making these proteins is stored in our DNA. The DNA consists of four molecules (commonly called by the letters A,T,G,C) put together in long strings of specific sequences. Each part of our DNA containing the information for creating a single protein is called a gene, thus our DNA holds the “genetic code” for all the proteins our body can make. The “letters” in our genes are converted to another type of molecular-letter-string called mRNA, which is then converted into protein.

Courtesy of Genetic Alliance UK

We get our DNA from our parents, and have a separate paternal and maternal copy of the entire human genetic code. However, sometimes you can inherit a gene that leads to disease — your DNA creates a slightly altered or dysfunctional protein that can affect certain processes going on in your body. For example, people with sickle cell disease have a gene for hemoglobin that is one “letter” different from the “normal” code. Hemoglobin is the protein inside your red blood cells that lets your body transport oxygen. When the code has been mutated through this one-letter change, it gives your red blood cells a sickle-like shape that can lead to many harmful effects.

Fixing a single base-pair mutation in our DNA could drastically change the shape of our blood cells, preventing sickle cell disease. Courtesy of Megan Hoban, UCLA.

Since many diseases are caused by very small alterations of our genetic code, it would be great if there was a way to change those codes carefully and correctly. While many methods have been designed to change the sequence of DNA, none of them are as easy to apply or as broadly effective as CRISPR-Cas, or simply CRISPR systems. CRISPR systems are groups of  proteins that are able to cut nucleic acids, like DNA, at specific points, when they have “guide RNAs” attached to them. To guide a CRISPR system to a pre-determined point in our DNA, we take advantage of the base pairing code. DNA is double stranded, and the letters A and G interact with the letters T and C on the other strand, respectively. Let’s say our target gene has an A at a specific position. Based on this complementary matching of letters, if we make our guide RNA have a T at the equivalent spot, it can interact with that A, too. Now if all the letters in our guide RNA are complementary to a certain gene sequence, the Cas protein will be chemically attracted toward that spot in your DNA. When it gets there, it will bind to the DNA, similarly to a Velcro strap, and make a precise cut. This way, we can make targeted small changes to specific genes causing known diseases, without causing any wide effects to the rest of the genetic code.

CRISPR interacting with DNA. Courtesy of Mirus Bio.

The ability to make site-specific cuts is an incredibly powerful tool in genetic engineering. Is there a protein you don’t want a cell to make? If you know the sequence of that protein, and therefore the sequence of its gene, you can cut it out. You can even add new genes by making a cut and putting something new in the middle — similar to ripping a piece of cloth apart and stitching a new fabric in the middle. With tools for genetic editing getting better every day, this is going to be a reality soon.

Even though CRISPR is a very powerful tool, there is plenty of debate in the scientific community about the rules that should govern its use in medicine. Since this method can be used to potentially eliminate diseases but also add features to organisms, important ethical issues have come up regarding use in animals and humans. The topic reached the news worldwide when a Chinese scientist, He Jiankui, announced that he used CRISPR to genetically modify two babies that were born through in vitro fertilization. The researcher had not received any official approval for these experiments and he was eventually fired from his position and is now facing prison time.

CRISPR ethics is still a fairly new field, but many government agencies like the National Institutes of Health have started working with bioethicists to study the best approach for regulating genetic editing. Since CRISPR is already widely used in research and even human clinical trials, scientists should always work in coordination with funding and governing agencies to continue exploring its benefits in an ethical and safe manner.  

— Devin Bog & Vicky Kanta

What are the Types of Kidney Failure?

Normal kidney function is fundamental for our health, since kidneys are tasked with removing waste from our bloodstream while keeping important nutrients. When kidneys stop performing this process, we are faced with a serious condition called kidney failure. Kidney failure is very prevalent worldwide, with approximately 5-10 million people dying every year from it. Since the human body has two kidneys, patients can survive if only one of the two is functioning. However, many times the conditions that damage our kidneys end up affecting both, which is why medical intervention is important.

There are two main categories of kidney failure: acute and chronic. The main difference has to do with the disease onset and progression rate. However, there may also be different underlying factors in their causes.

Acute kidney failure
In acute kidney failure (also called acute kidney injury), kidneys stop functioning over a very short period of time, usually a few days. There are many possible causes, but some of the most common ones have to do with decreased blood flow to the kidneys, direct injury to the kidneys or blockage of the urine pathway. Many times, acute kidney failure is a result of other conditions that bring patients to the hospital, which is why many times it occurs while patients are already hospitalized. Some examples are heart attacks, liver failure, or specific infections such as hemolytic uremic syndrome. Acute kidney failure is usually treated in the hospital with hemodialysis and dietary changes, until the kidneys restore their proper function.

Chronic kidney failure
In chronic kidney failure (or chronic kidney disease), the progression is slow and kidney function worsens over time. Some of the most prevalent causes are diabetes, hypertension and some genetic conditions that are associated with a family history of kidney failure. There are different stages of chronic kidney failure, measured by the ability of the kidneys to filter the blood. Based on the stage in which it is detected, chronic kidney failure can be treated with dietary changes and controlling the underlying condition. However, in late stages, special medication or hemodialysis may be required. If nothing else works, doctors may recommend a kidney transplant, which if successful may restore healthy kidney function.

Overall, kidney failure is treatable if detected early. Markers of deteriorating kidney function can be found in a simple blood test. This is why regular check-ups are important, especially if someone belongs to a group with a higher risk for developing kidney failure, such as diabetics, people with hypertension and older individuals.

More sources on kidney failure

  1. American Kidney Fund. https://www.kidneyfund.org/kidney-disease/kidney-failure/

  2. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/kidney-disease/kidney-failure

  3. National Kidney Foundation. https://www.kidney.org/atoz/content/about-chronic-kidney-disease

— Vicky Kanta

What is a Pandemic?

Whenever a new disease emerges, the term “pandemic” is very commonly heard on the news and social media. However, its definition is not always clear. Briefly, a pandemic occurs when a new disease spreads widely across multiple areas of the world. There are some key characteristics that separate a pandemic from other epidemiological terms, such as endemics and epidemics; experts declare a pandemic when a) the infectious agent (e.g. a virus) causing the disease is entirely new or sufficiently different from existing ones, b) the number of cases in each area exceeds what is expected based on the population (i.e., an outbreak), and c) there are increased occurrences in various parts of the world simultaneously.

virus 3d illustrationThere have been various pandemics throughout history, such as the plague, the Spanish flu, etc. Although pandemics can be caused by any highly infectious agent, most recent instances are associated with novel strains of the influenza virus, which causes the flu. The influenza virus mutates constantly and is highly infectious, which is why many pandemics are caused by it. For example, the 2009 H1N1 pandemic was caused by a new strain of the Influenza A virus. This strain had many differences when compared to the seasonal flu strains, which were sufficient to render the existing flu vaccine mostly ineffective, and required the development of a specialized vaccine.

Nowadays, most countries have emergency preparedness plans for the possibility of future pandemics. However, there are also some simple things we can all do to limit the spread of disease and infection, such as washing our hands frequently, avoiding contact with sick individuals, and covering our cough and sneeze using the inside of our elbow.

More pandemic resources

  1. World Health Organization. https://www.who.int/csr/disease/swineflu/frequently_asked_questions/pandemic/en/

  2. Centers for Disease Control and Prevention. https://www.cdc.gov/flu/pandemic-resources/basics/index.html

  3. Ready.gov – Department of Homeland Security https://www.ready.gov/pandemic

— Vicky Kanta