To become leaders in the field, biopharma companies must understand unmet needs and evolving standards of care and make greater use of real-world evidence.
Innovative therapies that target immune-mediated diseases have emerged as one of the fastest-growing fields in clinical research, second only to oncology in terms of ongoing clinical trials. The surge in interest is fueled by advances in the scientific understanding of the pathways that drive immune-mediated diseases and the immunotherapies that alter those pathways.
Inspired by therapeutic advances in oncology, some players are starting to view therapies for immune-mediated diseases as the next growth area for pharma companies. Competition is still, on average, less intense than in oncology, but we expect that pharma companies will seek to build on their successes to date.
A BCG study aimed to further such efforts by developing a comprehensive view of immune-mediated diseases. The study focused on understanding unmet needs and the evolution of standards of care for prominent diseases. To support our analyses, we developed a methodology to assess and compare unmet needs across diseases. (See “The Scope of the Study.”) We also built a machine-learning algorithm enabled by natural language processing to detect weak signals in clinical R&D that may be harbingers of major advances.
The findings highlight important differences among immune-mediated diseases with respect to unmet needs, the evolution of standards of care, and the level of clinical activity. Crucially, we found that leading companies are refining their clinical-trial strategies by better understanding the molecular similarities among clinically distinct diseases and analyzing real-world data to gain insights into the performance of mechanisms of action (MoAs) currently on the market.
For many years, oncology has been the primary focus for pharma companies and research institutions. The significant advances in disease understanding and new modalities have changed the treatment landscape, requiring companies to rethink their end-to-end commercialization process. Researchers’ recognition of the similarities among the molecular pathways involved in the pathogenesis of different diseases has had a particular impact—for example, in treating neuroendocrine tumors. The potential of molecular pathways as disease-agnostic targets is profoundly affecting development approaches.
We placed the immune-mediated diseases in the study into a single category based on the rapidly evolving understanding of human immunology at the molecular level. This reclassification revealed that these diseases are now in second place behind oncology as a focus for biopharma companies and the research community. (See Exhibit 1.)
Our analysis found that there were more than 1,100 ongoing clinical trials involving immune-mediated diseases in the US in 2021. Expanding interest in this field is likely due to increased knowledge in several areas:
Breakthrough scientific advances have promoted substantial growth in the US market for immune-mediated disease treatments, from $35 billion in 2004 to $120 billion in 2020. (See Exhibit 2.)
The share of revenues associated with treatments for musculoskeletal, nervous, and digestive diseases has gradually increased, but recent advances in treating skin-related diseases have boosted revenue share with respect to those as well. We have seen less change in revenue share from treatments for endocrine, renal, and vascular and systemic diseases.
The overall market has expanded as a result of several approvals of new MoAs in different therapeutic areas. (See Exhibit 3.)
These advances have significantly improved treatment efficacy for some diseases compared with the standard of care. But there remain significant unmet needs with respect to many diseases and organ systems.
Because of the similarities in the molecular pathways of different immune-mediated diseases, an understanding of unmet needs across diseases is helpful in identifying the evolution of standards of care and treatments. We developed a methodology to capture the different dimensions of unmet needs and selected a set of diseases to test and validate our results. (See “Methodology to Assess Unmet Needs.”)
Understanding unmet needs in immune-mediated diseases requires acknowledging that standards of care and treatments have evolved differently than in oncology, where efficacy generally trumps all other factors. Most immune-mediated diseases are chronic and not immediately life threatening. As a result, treatments are usually evaluated over longer periods and the relevance of safety increases. Additionally, given the chronic nature of immune-mediated diseases and the frequency of treatment, convenience plays a role in defining unmet needs. The impact of the benefits of safety and convenience varies across immune-mediated diseases. Their relevance relative to efficacy increases in the case of less severe diseases, where the focus is on disease modification and quality of life rather than on preventing or delaying death.
Although efficacy plays a role in immune-mediated disease treatment, demonstrating efficacy does not, by itself, justify switching treatments. The long duration of treatment means that a change is justified only if the improvement in efficacy is significant compared with the standard of care. One therapy may, on average, be superior to another, but there can be great variability among individual patients.
Our analysis found that unmet needs have been reduced significantly for some immune-mediated diseases, while for many others they remain relatively high. Exhibit 4 shows a selection of well-studied diseases. The level of unmet needs is primarily driven by an insufficient understanding of the biology of a given disease rather than the amount of clinical-research activity. However, some diseases have attracted more attention than others.
The number of MoAs with greater than $1 billion in sales is steadily rising. (See Exhibit 5.)
To understand how the competitive dynamics have evolved as the market has grown, we systematically reviewed approved MoAs across all known immune-mediated diseases since 2000. We identified four trends that are important for companies to consider.
To explore whether these trends related to late-stage development and approved MoAs are also reflected in early research, we built a comprehensive knowledge platform and tool based on natural-language-processing-enabled machine learning. We used these to detect trends in early research related to specific MoAs and diseases and in how researchers are seeking to use MoAs to treat diseases.
We found that researchers are exploring known and proven MoAs in multiple immune-mediated diseases across different organ systems. However, as we observed in the case of late-stage development and approved MoAs, the new MoAs under consideration tend to be focused on more prevalent diseases or on diseases with greater unmet needs. In addition, researchers are exploring MoAs for indications beyond immune-mediated diseases—for example, cancers and infectious diseases.
These findings indicate that clinical practice could provide many insights for research and clinical science to build upon. Such insights hold special promise for immune-mediated diseases, where epidemiology has proven that there is a higher probability of comorbidities—that is, two or more immune-mediated diseases occurring in the same patient.
Real-world data has untapped potential to systematically integrate insights from clinical practice with R&D. As molecule development strategies, including indication expansion, become more crucial for capitalizing on the competitive dynamics described above, biopharma companies can use weak or early signals to inform clinical trials. To date, few integrated real-world datasets or platforms exist for immune-mediated diseases, and companies are still grappling with specific challenges related to real-world data. However, past success stories, such as TNF-α inhibitors, have shown the value of applying a holistic and disease-agnostic perspective to a molecule when sequencing indications.
Pharma companies can use the following questions to guide their clinical R&D strategies for immune-mediated diseases:
Immune-mediated diseases are becoming an increasingly important field in clinical R&D. Researchers are only now starting to scratch the surface when it comes to understanding and treating these diseases. For biopharma companies, gaining a strong competitive foothold requires characterizing unmet needs and understanding the factors driving the evolution of standards of care. To become leaders in the field, they must leverage real-world evidence in order to integrate insights from clinical practice into their R&D decision making.
In the next article in this series, we will explore how companies can use archetypes of diseases with different patterns of evolution in standards of care to define their strategies