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IBD Clinical Trial Landscape: 3 Greatest Unmet Needs in IBD Clinical Development in 2023

Leave a Comment / News article / By Ashley Stufano

With the steady increase in the prevalence of inflammatory bowel disease (IBD) worldwide and the discovery of new disease pathways, there has also been a renewed interest in IBD drug development. During the ten years from 2010 to 2020, the number of clinical trials in the IBD therapeutic area almost doubled due to a combination of factors, including the continuous development of biologics, the discovery of new pathways, and, consequently, the introduction of new classes of medications such as JAK–STAT pathway inhibitors.

Our new white paper Inflammatory Bowel Disease: Current Status and Future Perspectives offers insights into recent trial and research developments that will most impact study design and operationalization for various IBD therapies and indications. In our previous post, we discussed the common challenges in IBD patient enrollment. In such a competitive landscape, it is also critical for drug developers to understand the major unmet needs in IBD management.

1. Lack of Predictive Biomarkers for Early Diagnostic Testing

There are a number of biomarkers, divided into two groups based on their application, currently used in clinical practice, but there is no single one that can help with an accurate diagnosis of IBD. The first group, aimed at diagnosis and monitoring of IBD, contains blood-based biomarkers of inflammation (C-reactive protein and erythrocyte sedimentation rate) and stool-based biomarkers (e.g., fecal calprotectin, fecal lactoferrin, fecal neopterin, and polymorphonuclear neutrophil elastase). The second group of biomarkers, aimed at the subclassification of IBD between UC and CD, includes blood-based biomarkers such as antineutrophil cytoplasmic antibodies (ANCAs), anti–outer membrane protein C (Anti-OmpC), anti–S. cerevisiae antibodies (ASCA), and anti-I2, anti-carbohydrate, and pancreatic antibodies.ⁱ These biomarkers can only be used as supporting data secondary to clinical data and endoscopic examination. Another limitation of biomarkers is their inability to predict response to therapy in patients with IBD.

2. Lack of Drugs with Minimal Side Effects

Conventional therapy methods, including 5-aminosalicylates, corticosteroids, thiopurines, anti-TNFs, and others, are generally effective in controlling symptoms, but adverse side effects such as immunosuppression, systemic fungal infections, and possible cancer development may have an overall negative impact on the disease outcome. There continues to be an unmet need for long-term treatments with minimal side effects, one of the greatest motivators for driving new IBD biologic development. For instance, all anti-TNF-α drugs in the US carry a boxed warning due to the increased risk of infections in 25–30% of patients, with limited treatment options afterwards. Etrolizumab was a potentially promising drug that was thought to close this gap, but as of November 2022, etrolizumab met its primary endpoint of inducing remission versus placebo for patients with UC in only two out of five studies and failed to meet its primary endpoint versus placebo as maintenance therapy.ⁱⁱ

3. Lack of Oral Drug Formulations

Based on the literature analysis and feedback from clinical trial investigators (and indirectly from the patients), the primary unmet need in management of moderate to severe IBD is lack of oral drug formulations: patients would prefer an oral formulation over the subcutaneous or intravenous administration. If the disease progresses further, requires hospitalization and IV corticosteroids, treatment options are limited with options of infliximab or cyclosporin, that in turn have significant side effects and they are at risk of toxic megacolon or bowel perforation with subsequent surgery. Prevention of this outcome is another focus of drug development – finding effective drugs for a late-stage disease.

Key Takeaways

IBD therapeutics and biologic developments have, thus far, not been able to provide substantial holistic solutions that improve a patient’s quality of life. More than that, limitations in testing, serious side effects, recalls and a lack of convenient therapeutic options have made minimal improvements upon current therapies. With the growing number of IBD studies, it is essential to consider and choose the right partner to help your IBD clinical trial stand out.

Despite the competition, PSI continues to deliver higher enrollment rates than typical across the industry due to our relationships with more than 3,900+ IBD sites around the world. Our studies are successful due to our long-term relationships with recruiting sites; we know the investigators on a personal level and they are motivated to work with us. Visit us online to learn more about our IBD therapeutic experience.

Meet our experts at DDW 2023!

Schedule a meeting to discuss your upcoming IBD trial in Chicago May 6-9.

References

ⁱ Soubières, A. A., & Poullis, A. (2016). Emerging Biomarkers for the Diagnosis and Monitoring of Inflammatory Bowel Diseases. Inflammatory Bowel Diseases, 22(8), 2016–2022. https://doi.org/10.1097/MIB.0000000000000836 

ⁱⁱ M. Agrawal, B. Verstockt. (2021) Etrolizumab for ulcerative colitis: beyond what meets the eye. Lancer Gastoenterology and Hematology 7(1): P2-4. https://doi.org/10.1016/S2468-1253(21)00369-1 

Top 4 Sponsor Challenges in IBD Patient Enrollment

Leave a Comment / News article / By Ashley Stufano

The number of IBD clinical studies grows each year; however, the number of patients enrolling in these studies has not increased proportionally. Instead, patient enrollment rates for IBD trials in recent years have shown a significant decline: from 1998 to 2018, the average recruitment rate in moderate-to-severe UC decreased from 0.32 to 0.13 patients per site per month, while the average recruitment rate in moderate-to-severe CD decreased from 0.65 to 0 to 0.10 patients per site per month.ⁱ

In PSI’s white paper Inflammatory Bowel Disease: Current Status and Future Perspectives, Senior Medical Advisor Maxim Kosov breaks down recent trends in IBD clinical research, including insights into patient recruitment and retention. Read on to discover the top four challenges to consider when enrolling IBD patients for your next trial.

1. Availability of Existing Treatments

The success of FDA-approved treatments, particularly vedolizumab in 2014, ustekinumab in 2016, and tofacitinib in 2018, often leads to a decreased patient enrollment rate in placebo-controlled randomized controlled trials. When the currently approved drug provides effective treatment with minimal side effects, patients will often opt for this method instead of enrolling in a study where they may receive a placebo drug. This is often a leading factor contributing to slow enrollment.

2. Competition Between Trials

When it comes to site choices and geomix, many sponsors and their partners approach larger academic centers first, assuming that these sites will have more experienced staff and equipment. One study found patients followed at academic centers are almost twice as likely to have participated in randomized clinical trials. However, the study also found over half of enrolled patients were followed in private practice settings.2 Focusing on large institutions leads to higher competition rates. For instance, as of October 2022, in the University of California San Francisco alone, there were 29 active IBD clinical trials, and 9 of them were enrolling.ⁱⁱ

3. Country and Site Selection

Additional factors may influence low enrollment potential, including site choice and geomix. When choosing the right geomix of sites, sponsors must consider the incidence of the disease, treatment standards, and availability of the medications. The incidence of IBD is increasing in Asia, Africa, and Latin America, driving interest in shifting clinical trials to these regions.ⁱⁱⁱ Additional factors to consider when selecting sites include the health insurance environment (the likelihood that insurance companies will approve less efficient generic medications over specialty ones) and the presence of preferred study sites (sites with whom the CRO has a long history of cooperation and appropriately trained study teams).

4. Screen Failure Rates

Over the past decade, screen failure rates in IBD trials have grown, approaching 50% in UC and 70% in CD, primarily due to failure to meet minimal endoscopic or biomarker criteria for active disease and a growing list of exclusionary concomitant medications. In PSI studies, we’ve seen a screen-out rate of 26-48% in UC and up to 64% in CD.

Some general recommendations to minimize screen failure and aid in patient enrollment rates include higher drug-to-placebo rates (such as a ratio of 2:1 or 3:1 rather than 1:1), broader use of patient-reported outcomes as the primary study endpoint, and optimization of study visits’ duration and complexity (including fewer procedures and endoscopies). Additional options for trial design include adding a long-term open-label extension for patients responding to therapy, and more involvement from the patient’s primary GI physicians at local hospitals and private practices. Primary care doctors see patients at the earlier stages of the disease course. There is a better chance that such patients are more likely to meet eligibility criteria than those admitted to larger hospitals or academic institutions, where the disease is often more severe and potential complications more frequent.

Conclusion

IBD patient recruitment and retention depends on the study protocol criteria and complexity, which must be scientifically sound to achieve the goals of the study as well as being attractive to patients. PSI provides a thorough review of the protocol by internal therapeutic area experts and harnesses the power of AI and machine-learning through our INTELIA ™ platform, combined with strong site relationships around the globe, to ensure your study meets enrollment goals. If you’d like to learn more about PSI can support your global Phase 2 and 3 IBD trials, click here.

References

ⁱ Harris, M. S., Wichary, J., Zadnik, M., & Reinisch, W. (2019). Competition for clinical trials in inflammatory bowel diseases. Gastroenterology, 157(6), 1457–1461. https://doi.org/10.1053/j.gastro.2019.08.020

ⁱⁱ Heyman, M., Terdiman, J., Lewin, S., Verstraete, S. G., & Mahadevan, U. (2022, November 7). UCSF inflammatory bowel disease clinical trials – San Francisco Bay Area. UCSF Clinical Trials. Retrieved November 21, 2022, from https://clinicaltrials.ucsf.edu/inflammatory-bowel-disease

ⁱⁱⁱ Ng, S. C., Shi, H. Y., Hamidi, N., Underwood, F. E., Tang, W., Benchimol, E. I., Panaccione, R., Ghosh, S., Wu, J. C., Chan, F. K., Sung, J. J., & Kaplan, G. G. (2017). Worldwide incidence and prevalence of inflammatory bowel disease in the 21st Century: A systematic review of population-based studies. The Lancet, 390(10114), 2769–2778. https://doi.org/10.1016/s0140-6736(17)32448-0