Cerecin’s Charles Stacey looks at the large unmet medical need in diseases of the central nervous system (CNS), the looming socioeconomic burden that these diseases represent, and the innovative solutions needed to counter it.


45 percent of the patient population in neurology remains unserved – they either have no access to treatment or have treatment with poor efficacy or side effects

Ask someone what the leading cause of death is globally. Most will say cancer, but they would be surprised to hear that in some western countries the leading cause of death is now Alzheimer’s disease and other dementias. Deaths due to dementias more than doubled between 2000 and 2016, whereas in contrast, the other leading causes of death– ischaemic heart diseases, cerebrovascular diseases, chronic lower respiratory diseases and lung cancer – have all seen falling mortality rates in the last 15 years. [1][2]


In recent years, oncology has been such a strong focus for the pharmaceutical and biotech industries that today, at least half of biotech companies target oncology. The once under-served oncology market is quickly growing as more patients receive adequate care.


A question to consider is why oncology has received this attention? Many of us have a relative or close friend that has been affected by cancer. It’s a very emotional experience seeing them go through the pain. We also know that we too are at risk of contracting cancer at any time of life. We are scared because it’s unpredictable and prevalent. This emotional pull of the illness has brought about strong patient advocacy in the sector, which has led to the research and development of more advanced treatment options.


For diseases that affect the Central Nervous System (CNS), the advocacy landscape now is roughly where oncology was a decade ago. It’s striking that 45 percent of the patient population in neurology remains unserved – they either have no access to treatment or have treatment with poor efficacy or side effects. But this large unmet need also presents an exciting market opportunity.


A rise in patient advocacy: a key driver for Oncology is now driving CNS

Patient advocacy has a strong role to play in fighting stigmas and creating disease awareness

Some CNS diseases such as Alzheimer’s Disease (AD), have faced stigma which prevents people from seeking medical treatment, receiving early diagnosis, requesting support or participating in clinical trials. This subsequently hinders AD research and the development of more advanced treatment options for patients that need them.


Patient advocacy has a strong role to play in fighting stigmas and creating disease awareness. This has been one of the key drivers for the development in oncology and is now gradually getting stronger for neurological disease.


We are seeing much more patient advocacy and visibility for CNS, such as the advocacy work of celebrities such as Terry Pratchett, in Alzheimer’s disease and Michael J. Fox for Parkinson’s. The amyotrophic lateral sclerosis (ALS) Ice Bucket Challenge, one of the most famous campaigns in recent years, is an example that has brought much-needed awareness to CNS disease.


These disease awareness campaigns help patients and the public to understand the disease, call for more resources to find more advanced treatment options and eventually a cure. The demand provides pharmaceutical companies incentives to develop the next generation of drugs, upgrading quality of care and puts government under pressure to subsidize the treatment. Another recent example of support from a high profile personality is the USD 50M commitment by Bill Gates to improve Alzheimer’s diagnosis. While clearly a very significant donation, the value of the endorsement and the subsequent public awareness is probably of greater value than the capital contribution itself.


Better understanding of the disease 

The pathophysiology in many cancers can be deciphered to a certain extent – by analysing a tumour, one is able to develop biomarkers and target treatment. It is more difficult for CNS. However, progress is being made as artificial intelligence (AI), imaging technology and analytical tools enable us to process more data and identify trends and insights faster.


We are also starting to apply some of the techniques used in oncology research to fast track our learning in CNS. This cross-pollination of research is allowing us to better understand the complexity of the disease and rethink our approach to the treatment.


What oncology has got right but is yet to be seen for CNS

Looking at the favourable environment provided for oncology drug development, there are also areas where CNS could be better supported. The transition from lab, to clinic, to approved drug is made easier in oncology thanks to clear regulatory objectives and clinical study endpoints to meet. For example, human survival and reduction in tumour size is a clear demonstration of the effectiveness of an oncology drug. On the other hand, many drugs in neurology fail in phase 3 as the measurements of success are not so straight forward. Furthermore, there may be a disconnect in Alzheimer’s disease in particular between what is required by regulators in many countries, and what is perceived to be of value by end users (persons with AD and their families).


There is also more innovation in oncology when it comes to clinical study design – it’s routine to have several investigative agents in one study. For example, instead of conducting a phase 1 trial to evaluate the toxicity and a separate phase 2 trial to evaluate the efficacy, we can consider combining these two objectives into one study to expedite the drug development. This is already a reality for areas like immunotherapy but needs to be adapted as well for neurology.


We need to act now

We are now at the tipping point, whereby the culmination of medical need, technology advancement, political pressure, ageing population, and past challenges have all come together

CNS presents a greater socioeconomic burden than oncology due to the longevity of the disease. The annual economic burden of brain-related illness in the US alone exceeds USD 1.4 trillion [3] (compared with USD 88.7 billion estimated for cancer).


Like all innovation, there are three critical factors for the success of CNS: money, people and science and technology.


More funding for research and drug development will incentivise new players. There also needs to be more successes cases, or a colossal success, to create a tipping point for new investments and hope for new drugs. The landscape now calls for one – there is a huge unmet medical need, and in Alzheimer’s for example, people and investors have lost money and trials have yet to succeed. A recent example is Biogen ended two Alzheimer drug trials, wiping out USD 18 billion from the capital market. Although investment from both public and private sources is now gradually building, more, much more, is needed.


There is a need for top people and for those people to be creative and think differently. Gathering extrinsic input from people outside of CNS – from oncology and even different industries would provide new perspectives to challenge the thinking of those within the CNS space. As the opportunity and need grows in neurology drug development, the hope is that the successful biotech veterans in the oncology sector will turn their eyes to the next underserved sector, CNS.


Advances in science and technology will be key to progress in neuroscience. There has been an explosion of research on biomarkers and imaging techniques. In addition, the rapid development in data science are helping us understand the data we collect in clinical trials and use these data to develop new hypotheses for further testing and develop a better understanding of fundamental disease pathophysiology.


We are now at the tipping point, whereby the culmination of medical need, technology advancement, political pressure, ageing population, and past challenges have all come together. We at Cerecin embrace this challenge with our commitment to developing solutions to address this emerging CNS disease crisis. We see an opportunity to significantly impact Alzheimer’s disease with our differentiated approach of tackling the metabolic deficit of the disease, with our drug candidate tricaprilin, that is gearing up for phase 3. As individuals, and as an organisation, we believe that a cure is possible, and we strive towards developing solutions to improve the lives of those suffering from Alzheimer’s and other neurological diseases.


[1] According to WHO

[2] According to Alzheimer’s Research UK

[3] According to Neuro-Insight