What’s the deal

Chronic Kidney Disease (CKD) is currently the 6^th fastest growing cause of deaths worldwide, where every year at least 2.4 million lives fall victim of the disease. In light of 2019’s World Kidney Day on 14^th March, we decided to take a look into this under diagnosed disease that has caught the attention of biotech start-ups and Big Pharma alike due to its growing market value, million dollar deals and increasing prevalence.

CKD is an insidious disease characterized by the gradual loss of kidney function over time and symptoms that only appear once the kidney’s function has already been significantly impaired. If not treated properly, CKD will progress to end-stage renal disease (ESRD), i.e. kidney failure, also known as CKD stage 5. At this stage, the only two options for survival available today is dialysis or kidney transplantation.

Rapidly growing prevalence and causes

Globally, 11-13% of adults are estimated to have CKD and, in the EU, 1 in 3 adults are estimated to be at risk of the disease. The most common causes of the disease is diabetes and high blood pressure (hypertension), but other factors, such as age, autoimmune or genetic diseases, extended use of painkillers and obesity also increases the risk of obtaining CKD.

A changing development pipeline

Right now, 88% of the marketed drugs in the CKD field are focused solely on treating the serious comorbidity of CKD, anemia, i.e. the loss of red blood cells. The development pipeline in the CKD space, however, is now shifting. Looking at candidates in Phase 2 and 3, 22 candidates out of 30 are aimed at treating either CKD or ESRD not a side effect. With today’s limited treatment options, the only choice is waiting for a kidney transplant, which in the U.S. takes an average of five years according to a national patient group, and until then, the patient is completely dependent on dialysis. The average life expectancy on dialysis is five to ten years. We’re afraid not a very bright outlook, making the possibility to provide a difference to these patients huge.

This surely demonstrates a serious interest from several big players in this under diagnosed, but growing $12.4Bn market.

Big interest from Big Pharma

For drug developers targeting CKD, it might be very interesting to know that over the last three years, deals with a total value of $1.6Bn has been struck in the field. To add to the case, several Big Pharma companies have expressed their interest in the field. AstraZeneca and Baxter are both global supporters of World kidney day and conduct research within the field. AstraZeneca describes CKD as one of their focus areas and is currently involved in the development of four drug candidates, of which two of these candidates are targeting CKD specifically. Baxter is instead focused on tools for dialysis that can improve outcomes for patients. Additionally, both Bayer and Eli Lilly have Phase 1 candidates for CKD in development. This surely demonstrates a serious interest from several big players in this under diagnosed, but growing $12.4Bn market.

The number of patients suffering from CKD is increasing every year, especially in western countries due to increasing prevalence of the risk factors, such as age, diabetes and obesity. Fortunately, the field and its patients has managed to catch the interest of pharma and biotech companies alike, motivating million-dollar deals with the potential of revolutionizing the way the disease is treated and perceived.

February 14^th marks Valentine’s day, a day traditionally dedicated to lovers and a day when a recent heartbreak may feel more painful than ever. A heartbreak, or ‘unwanted romantic breakup’ as research calls it, is one of the most painful experiences there is. But the silver lining is that pain is really ‘just’ a symptom modulated by the brain, meaning that it could be impacted by the placebo effect.

For as long as medicines have existed, there have been placebo treatments. A placebo is a treatment designed to simulate a medical intervention, but lacks a biological effect. In a primitive society, this could mean that the patient was ‘prescribed’ a month of being silent. In today’s society, however, it often refers to the administration of a sugar or dummy pill, mainly within the context of clinical drug trials. As a placebo treatment doesn’t affect the disease or injury in question, logic suggests that the treatment shouldn’t affect a patient’s symptoms. But it’s not that simple.

Why does the placebo effect work?

The placebo effect is, by now, a quite well-known term. It has been scientifically proven a number of times that even though the patient takes a dummy pill, they react as though (or close to) they’ve received the real medicine. The fact is that the placebo effect exists, however, exactly why it works remain ambiguous. The effect derives from both psychological and neurobiological mechanisms. One major part of the psychological mechanisms is expectations. We expect that a certain treatment will make us feel better and thus, it makes us feel better. Most likely, this effect is also reinforced by the people around you, who too believes that the treatment will work. However, there are also neurobiological mechanisms involved, where a 2015 study found that people with higher levels of dopamine or higher dopaminergic activity tend to be more likely to respond to placebo.

Why does the placebo effect work?

Exhaustive research on the subject of what conditions the placebo effect may influence has concluded that placebos mainly influence symptoms modulated by the brain. This refers to subjective and self-appraised symptoms such as pain, fatigue, nausea and hot flashes. Placebo treatments doesn’t, however, alter the pathophysiology of a disease, meaning that they rarely cure anything i.e. a placebo treatment cannot shrink a tumor nor restore damaged cells.

This means that the pain experienced in a heartbreak is just as real as the pain after breaking a leg.

How to mend a broken heart

In 2017, a group of researchers performed a study where they aimed to explore whether a placebo treatment could ease the pain of an unwanted romantic breakup. 40 volunteers were exposed to a photograph of their previous partner before and after being treated with a (placebo) nasal spray, which the researchers to half the group said had powerful properties for reducing emotional pain. Meanwhile, an MRI machine tracked the volunteers brain activity. The study found that, first of all, emotional pain was handled by the same parts of the brain as physical pain. This means that the pain experienced in a heartbreak is just as real as the pain after breaking a leg. Secondly, the researchers found that the group who believed that they were receiving a treatment that would reduce their emotional pain indeed experienced less pain. Additionally, the parts of the brain responsible for controlling pain were activated in this group.

According to the lead researcher, Leonie Koban, the implications of the study was not only a deepened understanding of the placebo effect but also that when it comes to heartbreak. Doing anything that you believe will help you feel better after a heartbreak will likely help you feel better according to a researcher specifically looking at the topic. Over the years, the placebo effect has been shown to reduce the difficulties experienced with asthma, diminish the pain of migraine and erase the pain of an injured knee. Since 2017, the pain of a heartbreak can be added to that list.

A final question about the placebo effect

But if the placebo effect is, at least partly, about expectations, won’t me knowing that it’s a placebo treatment hinder any placebo effects? Why would I expect it to work when I know that it doesn’t? Well, in a 2016 study from Harvard Medical School, researchers found that even when the patients knew that they were being treated with placebo, they still perceived an improvement of their symptoms. Fascinating, isn’t it?

Happy Valentine’s Day!