??Evolving Strategies in IBD Treatments: Competitive Landscape with KOLs Insights, Medicare Negotiations, and LoEs
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.?
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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:?
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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.?
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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.??
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The incidence peaks in early adulthood and then plateaus at a lower rate. The disease is less commonly diagnosed in Black, Asian, and Hispanic Americans.?
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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.?
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?Some Unmet Needs in IBD:??
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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. The introduction of biosimilars, particularly following the patent expiration of blockbuster drugs, is reshaping market dynamics by offering cost-effective alternatives that could potentially be used as step-through therapies before more innovative treatments.?
The competitive intensity in the IBD space is further exemplified by 默克 '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.?
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Looking ahead, KOLs emphasize disease modification and clearance as critical future trends in UC treatment. Combination therapies are gaining traction, with strategies such as using Upadacitinib for induction and Vedolizumab for maintenance being suggested. 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.?
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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 suggest that IL-23 inhibitors, particularly when combined with JAK inhibitors, hold significant promise for treating Crohn's Disease. Anti-TNF therapies, especially when used in combination with anti-IL23, are also highlighted for their potential efficacy. Additionally, anti-TL1A therapies are noted, although their full potential is still under investigation.??
However, there is also an emphasis on the need for anti-fibrotic drugs, which are seen as crucial for addressing the underlying fibrotic complications associated with Crohn's Disease. While combination therapies are seen as a step forward, they are not expected to completely revolutionize the treatment landscape on their own.?
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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.?
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Pharmacy Benefit Managers (PBMs) also play a pivotal role in this landscape. They negotiate drug prices on behalf of insurance plans and decide which drugs are covered, which can affect how accessible these treatments are to IBD patients. As some of the highlighted drugs like Stelara, Humira, and others approach their LoE, the dynamics within the market are expected to shift, potentially making some treatments more affordable.?
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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 the case of IBD there are so many treatments so having a clear understanding of where your asset will be positioned is key.?
During the clinical development, it is imperative to design clinical trials with the appropriate input from both commercial and access perspectives to ensure the inclusion of the right patient population and correct endpoints in your study will be added to maximize commercial & access.?
From Phase 2/3 onward, planning for the launch becomes crucial, involving market preparation and engagement with payers & KOLs.?
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Genchrome can assist:?
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Please contact: [email protected], we will get back to you.??
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By: Caroline BOULLIAT , Pharm D, CEO at Genchrome??
21 May 2024?
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