Here, Mark J. Field M.Sc. FRSB, FIScT, MRPharmS, Owner and Founder of Analgesic Innovation, discusses the ever-pressing need for Analgesic Innovation
Our pain detecting sensory system is an essential part of our body, keeping us safe, away from harm and aiding the healing process when we are injured. However, in various circumstances this system can malfunction and we are left suffering chronic pain.
The Pain Paradox:
“The sensory system that protects us from harm can malfunction and cause us Chronic Pain”.
In fact, it is estimated that chronic pain can affect up to 1 in 4 of us. Patients can wait years just for a diagnosis and even then treatment options are often limited with ‘standard of care’ medicines effective in around 1 in 8 patients. This creates misery for patients and their family’s placing huge burden on healthcare systems – financially as high as $635 billion annually, (higher than the costs for cancer, Alzheimer’s, and cardiovascular disease combined US figures).
Although there is clear huge medical need for new effective pain medicines (known as analgesics), the clinical success rate for developing an analgesic is 2% – five times lower than other therapeutic areas. This has led to an over reliance on historical drugs like opioids which in part has led to the opioid crisis seen in the U.S. The main role for any research and development is to bring innovative solutions to patients – but in the pain area we are clearly failing.
But there is hope… Investment in awareness of chronic pain and focusing on the right aspects of research can help create more precision analgesics and reduce patients time to diagnosis. Increasing disease understanding from involving patients and implementing this into research projects can dramatically increase the probability of success. The following principles are keys to success in analgesic innovation.
Understand the patient landscape
How many conditions are related to pain? A simple question but one that is very difficult to find an answer too. Whilst heading the Pain R&D area at Grunenthal I initiated a project spanning over 5 years which saw my talented colleagues source, collate and then validate with experts, conditions associated with pain. This immense piece of work identified over 100 conditions including some we previously had not been aware of. The conditions are available on PainLandscape.com.
100 vs 10: The hidden diseases
Current research in pain is mainly conducted in around 10 diseases which have a regulatory path to approval. However, there is clearly a large mismatch between the pain landscape (with 100 conditions) and the pain regulatory landscape. This is likely a key factor relating to the high attrition rate in pain R&D. New research drug targets have typically been identified and tested preclinically and then directed into specific patient groups relevant to the existing regulatory pathway rather than into patients linked to the experimental target. This makes sense in one way, as many trials have been run previously in these conditions and it is possible to give highly accurate cost and time estimates for these trials. However, this fixation on following the already beaten path has led to such high attrition. If we want real chances of success we need to explore the other ‘hidden diseases’ identify targets from understanding the disease and run trials in those patients.
The gender bias and time to diagnosis
Talking to patients and gathering data to map out their patient experiences gives rise to multiple highly valuable insights. Looking across a number of different patient groups we found some similarities between them. One quite shocking and impactful finding was the time taken to diagnosis.
It was not uncommon for patients to be waiting years, and if you are a woman you are likely to be waiting years longer than a man. This innate sex bias against women is a huge topic in itself, women will suffer with chronic pain conditions more than men but most research is conducted in males. We need to find ways to increased female-focused research and develop projects in female pain disorders like endometriosis and vulvodynia.
“Increasing disease understanding from patients and implementing this into research projects can dramatically increase the probability of success.”
The right clinical endpoint
In clinical development a patient’s pain is typically rated on a numeric scale, from 0 (no pain) to 10 (worse pain imaginable). Although this is a simple and quick assessment tool it is very subjective leading to huge variations in data captured and is one of the reasons for the need for large patient numbers within trials. Perhaps more importantly the scale is quite irrelevant to a pain patient. They will typically describe key endpoints that would mean success from a new therapy as, improvements in sleep, ability to increase physical function, increased social interaction, increased engagement with their partner, amongst many others.
Importantly, the most significant endpoints for patients may differ between different pain conditions.
Therefore, early engagement with patients allows the potential for the development of a specific ‘patient reported outcome – PRO’ that can be used within the clinical trials. This does come at a cost of time and money but could be key for successful drugs to differentiate from current standard of care and convince payers to reimburse the product.
Link target to disease
Historically most R&D follows the same pattern, with preclinical research identifying a new target which is validated in preclinical models. Its clinical validation only coming some 10 years later when it is tested in patients for the first time. Unfortunately, many companies are still following this same development path today, with limited preclinical to clinical translation. Unless we change, the attrition rate will get even worse and patients will not see the innovative new therapies they desperately need. By investing in patient centred research, it is possible to identify new targets from further understanding of the biology of the disease.
The way forward
With governments, patients, academics and industry working together to increase awareness of chronic pain in a broad and holistic fashion it could be possible tackle the gender bias and to reduce patients time to diagnosis by years.
For the general health and wellbeing of our society it is important that we invest in research to develop new analgesics. Academics, Biotechs and pharmaceutical companies who invest in the principles discussed above and embrace patient engagement in early R&D are likely to be the long-term winners, helping patients and creating valuable reimbursable precision analgesics.
*Please note: This is a commercial profile