As flowers bloom and nature welcomes spring in the Northern Hemisphere, we are amidst a season of change. However, for those navigating the Rheumatoid Arthritis (RA) market, change remains uncertain. Just as nature follows cyclical shifts, markets undergo transformations, albeit with less predictability. In the realm of RA, it seems we may linger in autumn for a while longer, awaiting the arrival of a new season.
Over the past few decades, the RA market has been one of the most significant and dynamic sectors in the pharmaceutical industry. It has introduced several blockbuster drugs that have cumulatively totalled a whopping US 477 BN[1] in revenue over the past 10 years, with Humira emerging as the top-selling drug of all time. However, as with many other therapeutic areas, the RA market is now facing its own challenges, with a predicted market value decline at a CAGR of 6.9% from 2022 to 2028[2]. This decline stems from the influx of biosimilar drugs and a dearth of breakthrough late-stage pipeline drugs.
Stepping into this arena presents significant challenges. The abundance of branded treatment options, spanning various mechanisms of action (MoA), coupled with mounting pricing pressures from biosimilar competition, creates a daunting landscape for drug development. The wide array of choices and the high levels of efficacy of modern treatments have notably enhanced disease management and reduced the demand for new pharmaceutical options. A 2022 publication in Nature Review by Finckh et al.[3] confirmed this trend, indicating a decline in the severity and long-term consequences of the disease. With that, the pivotal question arises: should drug developers let the leaves fall and halt investment in RA innovation?
Examining clinical development in RA, it’s evident that the number of industry-sponsored Phase 1-3 studies has declined. Between 2013 and 2018, 276 studies were initiated, but from 2018 to 2023, that number dropped to 102. Furthermore, there is currently no innovative drug in global Phase 3 development for RA. So, what will it take for the market to embrace new innovative solutions when the existing newer medications already achieved significant levels of remission and nearly 80% ACR20 efficacy in clinical trials?
While the answer remains elusive, we believe in the cyclical nature of innovation. Sometimes, the most intriguing solutions emerge in the face of adversity. Let’s explore some options:
Find New Seeds
The use of artificial intelligence in drug discovery and continued study on the pathology of RA will continue to lead to the identification of new targets considering the complex, multifactorial, and varied ways the disease presents in different patients. New technologies and delivery systems could also offer targeted treatment options with the potential to address the safety concerns of current systemic medications.
Divide the Crop
Personalized medicine is the holy grail, tailoring treatments to individuals rather than the masses. In RA, this would entail diagnostic and biomarker-driven approaches, stratifying patients based on their specific disease drivers. The success of personalized approaches in oncology provides a promising framework. The co-development of RA drugs alongside predictive biomarkers holds potential for elevating treatment efficacy beyond current standards, thereby potentially streamlining reimbursement pathways with payers. Furthermore, considering the extensive scope and complexity of RA programs targeting the general patient population, personalized medicine offers a viable avenue for significantly reducing research costs. However, challenges such as poor pathogenic understanding of RA, limited access to diagnostic testing, and no active stratification of patients into sub-populations remain hurdles.
Graft into New Trees
RA’s complexity and the multisystem impact of the immune system offer numerous opportunities to uncover its broader implications in human health. Analogous to diabetes, which led to innovative repurposing of drugs in associated disease areas like obesity, heart failure, and kidney disease, RA could have similar potential. Exploratory work on this can be found in areas like diabetes and cardiovascular diseases, including research on the effects of TNF inhibitors to treat diabetes or IL-6 inhibition to treat myocardial infarction and heart failure. Use of RA drugs in other disease areas commonly shared by RA patients would build up the profile of the drugs in RA, and help create a more compelling proposition for payers, patients and HCPs.
In this season of transition, the landscape of the RA market may be ripe for renewal. Just as leaves shed and new blooms emerge, there’s potential for fresh innovations in Rheumatoid Arthritis. For drug developers willing to navigate the risks of innovation in a mature market, there’s a vast terrain waiting to be explored. While there are various avenues to success, the most fruitful approach may involve a holistic strategy that considers the complex needs of RA patients. Katz et al.4’s recent review supports this notion, revealing that patients with RA experience a higher prevalence of multimorbidity (31-86% vs 18-71% in non-RA) and a faster accumulation of comorbidities. The authors also noted that patients with RA and multimorbidity are at increased risk of high RA disease activity while experiencing a lower likelihood of biologic use and more biologic failures. This underscores the complexity of RA management and highlights the importance of multisystem approaches.
Similar to the transformation seen in diabetes treatment, revolutionized by a change in thinking and incorporation of cardiorenal assessments for treatment selection, approaching the market by looking beyond the traditional bounds of RA research will likely be imperative to achieve significant success. Exploring mechanistic pathways in RA with potential impacts on other organ systems could be the initial step. Then, innovating trial designs to incorporate endpoints beyond RA-related benefits could bolster the case for value, offering opportunities for improved reimbursement. Moreover, such data could catalyze dedicated studies in other medical areas.
Sources
1: evaluate pharma (cumulative total revenue generated by RA drugs that achieved 1bn in sales at any point between 2013-2023)
2: evaluate pharma
3: Finckh, A., Gilbert, B., Hodkinson, B. et al. Global epidemiology of rheumatoid arthritis. Nat Rev Rheumatol 18, 591–602 (2022).
4: Katz J, Bartels CM. Multimorbidity in Rheumatoid Arthritis: Literature Review and Future Directions. Curr Rheumatol Rep. 26, 24-35 (2024) doi: 10.1007/s11926-023-01121-w.