This week marks the highly anticipated Digestive Disease Week (DDW)! DDW provides an unparalleled platform for the latest research and advancements in the field.
For the occasion, let’s delve into current treatments for IBD, and explore the insights and developments shared by Key Opinion Leaders (KOLs) regarding the most promising treatments and future trends for IBD, including Crohn’s Disease and Ulcerative Colitis. We will also examine the impact of Medicare and Loss of Exclusivity (LoEs) on current and future treatments.
Introduction to Inflammatory Bowel Disease (IBD)
Inflammatory Bowel Disease (IBD) encompasses a group of chronic, recurrent inflammatory conditions of the gastrointestinal (GI) tract. The two primary types of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). These conditions affect approximately 2-4 million individuals in the U.S. and over 5 million worldwide. Characterized by intermittent flares and remissions, IBD significantly impacts patients’ quality of life due to its unpredictable nature.
UC and CD are distinguished by their specific areas of inflammation. UC is confined to the large intestine and rectum, presenting with continuous inflammation. In contrast, CD can affect any part of the GI tract and is noted for its discontinuous inflammation.
Signs and symptoms that are common to both Crohn’s disease and ulcerative colitis include:
- Diarrhea
- Fatigue
- Abdominal pain and cramping
- Blood in your stool
- Reduced appetite
- Unintended weight loss
The etiology of IBD remains complex and multifactorial, with genetic, environmental, and immune-related factors contributing to its pathogenesis. It is particularly prevalent in countries with Western lifestyles, suggesting a potential link with diet and hygiene practices.
Dr. Alsabbagh and his team, including lead researcher Miguel Regueiro, MD from Cleveland Clinic’s Digestive Disease & Surgery Institute, searched a large electronic health record database called Explorys. They looked for adult patients diagnosed with Crohn’s disease or ulcerative colitis from 1999 to 2022 across 26 major U.S. health systems. Within the Explorys database, which includes records of about 70 million people, they found 458,419 patients (or 0.65%) with IBD. Of these, 54.4% had Crohn’s disease (249,429 patients) and 45.6% had ulcerative colitis (208,990 patients). About 8% of these patients were Black and 76% were white.
Incidence peaks during early adulthood and then levels off at a lower rate. Specialists diagnose the disease less frequently in Black, Asian, and Hispanic Americans
Current Treatments and Unmet Needs in IBD
Initial management of IBD typically involves the use of 5-aminosalicylic acid (5-ASA) compounds, especially for mild cases. As the severity increases, treatment escalates to corticosteroids and immunomodulators like methotrexate to induce remission. However, these conventional treatments often fail to maintain long-term remission, leading to the use of more advanced therapies such as TNF inhibitors and integrins.
For moderate to severe cases that show inadequate response to initial treatments, the therapeutic strategy includes anti-TNF agents, integrins, and other biologics targeting interleukins (ILs), Janus kinases (JAKs), and sphingosine-1-phosphate receptors (S1Ps). Despite the availability of these treatments, a significant unmet need exists for patients who are refractory to current options, with many cycling through various therapies due to diminishing responses over time.
Some Unmet Needs in IBD:
- Risk Stratification: Early aggressive treatment can prevent severe outcomes, but identifying who needs it remains difficult. Improved, validated biomarkers are essential.
- Personalized Therapy: IBD varies widely among individuals, requiring more precise biomarkers to tailor therapies based on individual risk profiles and treatment responses.
- Therapeutic Ceiling and Sequencing: Many patients do not reach remission with current treatments, highlighting the need for better therapy sequencing and combination strategies.
- Special Populations: Addressing treatment for specific groups such as patients with perianal disease, the elderly, and those with refractory conditions is critical, as these populations often have poor outcomes with standard treatments.
- Monitoring and Prophylaxis: Healthcare providers need effective non-invasive monitoring tools to assess disease progression, treatment response, and strategies to prevent post-operative recurrence.
- Quality of Life: Beyond controlling disease, improving overall quality of life and managing symptoms like fatigue and psychological impacts remains a significant need.
- Therapy De-escalation: Developing safe strategies to reduce or stop treatment while maintaining remission is crucial, particularly for patients responding well to biologics.
IBD: Competitive Landscape and New Treatments
The IBD treatment landscape is highly competitive and dynamic, underpinned by a robust pipeline of novel therapies aimed at addressing unmet needs. Biosimilars are reshaping market dynamics, especially after the patent expiration of blockbuster drugs, by offering cost-effective alternatives that may serve as step-through therapies before more innovative treatments.
The competitive intensity in the IBD space is further exemplified by Merck‘s recent acquisition of Prometheus Biosciences, Inc. for an estimated $10.8 billion. This strategic move highlights the industry’s focus on diversifying portfolios and enhancing inflammation and immunology (I&I) capabilities. Prometheus’s lead asset, PRA023, has shown promising Phase 2 results in UC and CD, offering potential pipeline-in-a-product advantages with JAK inhibitor-like efficacy but a superior safety profile.
Ulcerative Colitis (UC): Promising Treatments and Future Trends | Genchrome Insights from KOLs
Genchrome surveyed KOLs specialized in the field of Inflammatory Bowel Disease (IBD), and they have identified several promising treatments and future trends for Ulcerative Colitis (UC). JAK inhibitors are highlighted by experts for their rapid onset and potential for achieving complete remission. Anti-IL23 therapies are also considered significant due to their targeted approach in modulating the immune response. Additionally, the potential of anti-TL1A therapies is noted, though more evidence is needed to confirm their efficacy.
KOLs highlight disease modification and clearance as critical future trends in UC treatment. Combination therapies are gaining traction, with strategies like using Upadacitinib for induction and Vedolizumab for maintenance. Experts recognize the challenge of maintaining the efficacy of JAK inhibitors over time, proposing a combination therapy approach that integrates JAK inhibitors with a maintenance therapy to balance rapid onset with long-term safety and durability.
Crohn’s Disease Promising Treatments and Future Trends | Genchrome Insights from KOLs
Promising Treatments:
The future of Crohn’s Disease treatment appears to be leaning towards combination therapies. Experts widely discuss the potential of combining different therapeutic agents.
KOLs highlight the potential of IL-23 inhibitors, especially when combined with JAK inhibitors, for treating Crohn’s Disease. They also emphasize the efficacy of anti-TNF therapies, particularly in combination with anti-IL23. While anti-TL1A therapies show promise, their full potential remains under investigation.
Additionally, there is a strong focus on the need for anti-fibrotic drugs to address the underlying fibrotic complications in Crohn’s Disease. While experts view combination therapies as a positive step forward, they do not expect these treatments to fully transform the landscape on their own.
IBD: The Impact of IRA Negotiations and LoEs
The Inflation Reduction Act represents a significant shift in how drug prices are negotiated within the U.S., particularly for Medicare. This legislation allows for the negotiation of drug prices, which can directly affect the cost and availability of IBD therapies. As patents expire (Loss of Exclusivity), biosimilars and generics enter the market, potentially lowering costs but also intensifying competition. For healthcare professionals, understanding these changes is crucial as they can impact prescribing patterns and patient access to medications.
Pharmacy Benefit Managers (PBMs) play a pivotal role in this landscape by negotiating drug prices for insurance plans and deciding which drugs are covered, which directly affects how accessible these treatments are to IBD patients. As Stelara, Humira, and other drugs approach their Loss of Exclusivity (LoE), shifting market dynamics will potentially make some treatments more affordable
Genchrome Key Insights:
During the preclinical stage, it’s essential to build the TPP to ensure your asset captures unmet need and represents a commercially viable asset. Understanding where to position your new drug in the treatment pathway is essential.
In IBD, you must clearly understand where to position your asset among numerous treatment options. During clinical development, it’s essential to design trials with input from both commercial and access perspectives to ensure the inclusion of the right patient population and the correct endpoints, maximizing commercial success and market access
From Phase 2/3 onward, planning for the launch becomes crucial, involving market preparation and engagement with payers & KOLs.
Genchrome can assist:
- In building your insights ( eg- KOL; payers interviews, Advisory Boards)
- In Building your strategy (eg.TPP, Positioning, differentiation , unmet need)
- In Valuation of assets
- In supporting licensing in/out of IBD assets or other relevant partnerships.
Please contact: contact@genchrome.com, we will get back to you.
