by Dr. Pierre Eftekhari, CEO of Inoviem Scientific and Bcell Design
Chronic diseases are becoming increasingly prevalent worldwide and show no signs of decline. Across 26 OECD nations, over one-third of adults aged 16 and older reported having a chronic disease or health condition on average. In order to meaningfully deliberate upon the implications of chronic diseases for the pharma industry, it’s important to truly understand the challenges in addressing these chronic diseases.
Firstly, the challenges are multifaceted- safe, effective and affordable treatments that can meet the complex needs of patients have to be developed while also traversing regulatory and financial pressures and barriers in the field.
Complex Diseases
The complex and multifactorial nature of chronic diseases pose significant challenges in the development of effective drugs. Take their heterogeneity for instance; diseases such as cancer, diabetes, and cardiovascular diseases can have multiple subtypes, each of which could further differ in terms of molecular drivers and clinical outcomes. With high heterogeneity concerning their underlying causes as well as their clinical manifestations, developing drugs across all subtypes or stages of the disease is undeniably difficult. This means each subtype or stage requires special attention and personalized approaches to achieve potent solutions.
When it comes to multiple causative factors, one should keep in mind that it could range from behavioral and lifestyle factors to environmental and genetic factors. To exacerbate the challenge, these factors also interact in complex ways, making it difficult to identify the most relevant targets for drug intervention among them. Further, designing drugs efficient enough to modulate these targets is yet another tough task ahead.
More often than not, in the case of chronic diseases, the lack of well-defined and reliable biomarkers, which are measurable indicators of disease status or drug response, stand in the way of adequately stratifying patients, monitoring treatment response and predicting outcomes. This difficulty also adds to the challenge of identifying the right patient populations for clinical trials.
Regulatory Challenges
The regulatory approval process for drug development is complex, costly and time-consuming as it is, given the rigorous standards for demonstrating safety and efficacy that takes into consideration data from both preclinical and clinical studies. Keeping up with the dynamic nature of the regulatory landscape also demands a considerable amount of attention to be focused on changing guidelines, requirements and standards. Taking into account the unique set of challenges attributable to the process of developing drugs for chronic diseases, as discussed above, obtaining regulatory approval is even more laborious.
To add to that, the fact that chronic diseases require long-term treatment and monitoring also means that the outcomes of the treatment may take time to manifest. This, in turn, translates to the need for conducting clinical trials with sufficiently long durations to capture meaningful data on long-term safety and efficacy, as is often required by regulatory bodies for approval. For chronic diseases, the benefits of a drug may take time to outweigh the potential risks or side effects that accompany it. This necessitates a thorough evaluation of the risk-benefit profile of the drug, which considers a number of factors such as long-term safety, efficacy and potential side effects. Demonstrating desirable clinical outcomes will also require a careful navigation of a tricky regulatory landscape, given the lack of well-defined or established endpoints or biomarkers.
Rising Healthcare Costs
Rising healthcare costs have multiple implications for patients, especially affecting those who require long term treatments, which is the case for chronic diseases in general. Then there’s the added cost of treatment in case of side effects that have to be treated with other drugs. Incentivizing innovation to produce new cures through high product prices puts strain on consumers to be able to afford their drugs, with the cost of innovation passed on to them in the form of high prices. Many times, it also happens that many new products are priced highly, almost disproportionate to their actual value in terms of added clinical advantages over what’s already available in treatments. At the same time, there is also an absence of new products to cater to important illnesses and issues that continue to threaten human health, including tuberculosis and anti-microbial resistance.
Other Challenges
Besides the happenings within the industry that directly impact drug development, broader global trends also affect the pharma industry’s approach to chronic diseases. Take supply chain pressures for instance; inflation has risen considerably in recent times, leading to increasing costs of labor, raw materials and transportation- going above and beyond the persistent price pressures already faced by pharmaceutical companies. The pharma industry may appear to be somewhat shielded by its high inventory levels and long-standing dual sourcing, but the likelihood of supply chain disruptions still represents a potential loss of 25% of EBITA. Supply chain pressures can also negatively affect the availability of raw materials including active pharmaceutical ingredients (APIs) and other components critical for drug development. Such delays and interruptions can unfavorably impact the timeline, cost, quality, and meeting regulatory requirements, making successful drug development challenging.
What Can Be Done?
Patient-centric approach: Efforts deviating from clinical reality and unmindful of its related complexity would generate misleading knowledge for drug development. The translational approach must meet at least the following three requirements-
- Biological complexity
- Biological diversity
- Physiological and pathological dynamics
The sum of interactions required to maintain the physiological or pathological dynamics varies intra-individually. Therefore, drug development should be guided for any given pathology by the group of responder patients and not all the patients with the same pathology.
Multidisciplinary approach: To completely understand and accommodate the aforementioned complexities while developing treatments, there is a need to go beyond the obvious and incorporate information, insights and knowledge from various disciplines including pharmacology, genomics and bioinformatics. Not only does a multidisciplinary approach lead to more comprehensive and holistic solutions- it can also potentially accelerate the drug development process for chronic diseases. Pooling together diverse perspectives, ideas and techniques means innovative solutions and novel approaches have more chances of coming to fruition in comparison to unidimensional approaches that solely focus on solving a problem from singular angles alone.
The need for personalized medicine: By recognizing and acknowledging that each patient is unique and may respond differently to treatment, the likelihood of successfully developing personalized treatment plans also increases. New technologies that can effectively help identify molecular variations that may affect drug responses is the need of the hour. The right patient at the right time translates to effective and personalized treatment tailored to each patient and will lead to better patient care and thus reduce financial pressures on health systems and patients. For instance, think about how personalized treatment could reduce unwanted side effects that may otherwise require new medication to treat.
Focus on accelerating new technology to cope with rising costs: Initiatives such as investing in public research through the National Institutes of Health (NIH), supporting biopharma startups with access to capital through existing programs such as Small Business Innovation Research (SBIR) and publicly funding targeted clinical development programs such as Biomedical Advanced Research and Development Authority have in the past proven to help meet needs that are pressing yet unmet. For instance, by publicly funding targeted clinical development of drugs through BARDA, substantial resources can be allocated to developing drugs for chronic diseases that are identified as public health priorities. Publicly funded research can achieve what is often not feasible for private companies to undertake due to financial or resource constraints and could deliver long-term, high-risk research built on a solid foundation for drug development.
In short, public funding can help expedite the drug development process while also providing additional support in advancing promising drug candidates and the availability of innovative treatments for chronic diseases.
Label free technologies for drug development: With the potential to revolutionize drug development by providing a more comprehensive and efficient approach to identifying and characterizing potential drug candidates, label free technology allows researchers to study the binding of drug candidates to target molecules and assess their potential efficacy. This is possible thanks to the technology’s ability to provide real-time measurements of biomolecular interactions, enabling researchers to study binding kinetics and affinity in situ. These biomolecular interactions could include protein-protein interactions, protein-nucleic acid interactions, protein-small molecule interactions and so on. This helps increase the confidence of researchers by equipping them with a more comprehensive and systematic understanding of the interactions between potential drug candidates and their targets.
As practitioners are enabled to holistically understand the biological mechanism of a disease, a drug candidate’s mechanism of action and the origin of its side effects, they are also better equipped to identify relevant biomarkers related to a disease or a drug candidate, so as to prepare the most effective and targeted treatment possible. Additionally, label-free technology, given its ability to rapidly analyze multiple samples in parallel, also accelerates drug discovery and reduces the time and cost associated with drug development methods traditionally followed. This, in turn, translates to high-throughput screening of potential drug candidates.