Disease Analysis: Ulcerative Colitis
Author: Jeff Stevens
Publisher: Datamonitor Healthcare
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Disease Overview
Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease (IBD), which causes mucosal inflammation affecting the colon. The idiopathic inflammation is commonly associated with the rectum (proctitis) and may extend proximally, evolving into left-sided colitis or extensive colitis (see the figure below). UC typically presents with bloody diarrhea, which may manifest alongside mucus, rectal urgency, tenesmus, and abdominal pain. The disease course is relapsing and remitting with intermittent periods of acute exacerbation, which may be serious enough to warrant therapy escalation, hospitalization, or even colectomy.
Latest key takeaways
- As specialty products, therapies for ulcerative colitis (UC) can be expensive, and formulary positioning is paramount to product uptake. Payers are settled in vital contracts that lead them to prioritize broad immunology drugs Humira and Remicade. This has posed a high barrier to newer entrants to the market, which cannot compete in volume and rebates. Biosimilar and generic competition will further undermine the likely premium pricing of newer and pipeline products.
- Pivotal upcoming events in the forecast period include the entries of biosimilar adalimumab and generic tofacitinib. Biosimilar adalimumab will enter the US market from 2023, while generic tofacitinib is expected to enter the US market at the end of 2025. Notably, generics have fewer barriers to entry than biosimilars due to numerous factors, including their less complex nature and long-standing familiarity, which facilitates much faster and stronger erosion of branded sales.
- Nevertheless, the UC market is projected to expand, propelled by a growing patient caseload and the introduction of pipeline products. Datamonitor Healthcare estimates that in 2018, there were 12.6 million prevalent cases of UC worldwide, and forecasts that number to increase to 13.5 million prevalent cases by 2027.
- The UC pipeline holds multiple novel prospects in terms of distinct mechanisms of action and biologics with more convenient formulations. The market will welcome sphingosine 1-phosphate (S1P) receptor modulator etrasimod, interleukin-23 (IL-23) modulator mirikizumab, and toll-like receptor (TLR) 9 modulator Kappaproct. There has been a positive response to Xeljanz as the first novel oral drug competing with biologics for UC, and other companies have recognized this opportunity to provide ease of administration, for example with oral etrasimod and Rinvoq. Once these products reach the market, they will provide more options for UC patients beyond the established, non-oral anti-TNF class, which is currently the mainstay of treatment. It is likely that these novel products will initially compete at later lines of therapy after the anti-TNF inhibitors, given the latter’s enduring stronghold at the first line of biologic therapy.
- Zeposia (ozanimod), an S1P receptor modulator, was approved by the US FDA in May 2021 for patients with moderately to severely active UC. Zeposia will hit the market sooner than etrasimod and has a more attractive commercial profile.
- Although the anti-TNF class are the cornerstone of treatment, ~10–30% of patients are non-responders to initial treatment and ~23–46% of patients lose response over time. Additionally, the class has black box warnings for the risk of serious infections and malignancy. These drugs are favored due to long-standing physician familiarity and prioritization in formularies; however, they do not satisfy persisting unmet needs in the UC market.
- Critical unmet needs and opportunities include demonstrating strong efficacy to treat inadequate responders, clinically balanced drugs that offer both efficacy and safety, producing superior data over anti-TNF inhibitors and available drugs in the same class through head-to-head trials, and competitive pricing, which is essential to facilitate better positioning in the treatment algorithm.
- Entyvio is forecast to take a top spot in the UC market, with estimated global sales of $3,893m in 2021 and steady increases over the coming years.
- Topline results from the MANTA Phase II study of Jyseleca (filgotinib) demonstrated a numerically lower proportion of Jyseleca patients experiencing a >50% decline in sperm concentration (6.7% vs 8.3% on placebo). This provides initial reassurance for Jyseleca’s prospects in the US following safety concerns pertaining to the 200mg dose that caused the FDA to issue a complete response letter to the approval application in rheumatoid arthritis.
- The most anticipated future events include a European supplemental CHMP opinion for Zeposia in October 2021, and topline results from the Phase III LUCENT-2 study for maintenance treatment using mirikizumab by the end of the year.
CONTENTS
8 OVERVIEW
8 Latest key takeaways
10 DISEASE BACKGROUND
10 Definition
10 Patient segmentation
12 TREATMENT
12 ACG treatment guidelines
12 ECCO treatment guidelines
12 NICE treatment guidelines
28 EPIDEMIOLOGY
28 Prevalence methodology
31 MARKETED DRUGS
39 PIPELINE DRUGS
49 KEY REGULATORY EVENTS
49 Sorrento And Mabpharm Get ‘Biobetter’ Infliximab Approval In China
49 ANI Refiles Cortrophin After Talks With FDA
49 Zeposia’s Ulcerative Colitis Approval Provides BMS’s Beachhead Into GI
49 Alberta Expands Biosimilar Switching With Adalimumab
50 Sandoz Confirms Launch Of Humira Rival In Canada
50 Celltrion Wins Global First Approval For High-Concentration Humira Biosimilar
50 Celltrion Wins Race For High-Concentration Adalimumab
51 Tentative Xeljanz XR Approval Among Several For Zydus Cadila
52 PROBABILITY OF SUCCESS
53 LICENSING AND ASSET ACQUISITION DEALS
53 LianBio Gets Two GI Candidates From Landos
53 LG Chem, TransThera Agree To Immune Disease Partnership
53 Merck & Co. Buys Pandion, Building Out Capability In Autoimmune Disease
53 Scipher Hopes IBD Alliance With Galapagos Is The First Of Many
55 CLINICAL TRIAL LANDSCAPE
56 Sponsors by status
57 Sponsors by phase
58 Recent events
63 DRUG ASSESSMENT MODEL
63 Biologic disease-modifying antirheumatic drugs (DMARDs)
65 Non-biologic DMARDs
68 DNA-based immunomodulatory sequence
69 MARKET DYNAMICS
70 FUTURE TRENDS
70 Novel pipeline products are poised to diversify the UC market
70 Brands will face headwinds as the UC market is penetrated by biosimilars and generics
72 CONSENSUS FORECASTS
78 RECENT EVENTS AND ANALYST OPINION
78 Multiple Drugs for Ulcerative Colitis (September 1, 2021)
79 TD-1473 for Ulcerative Colitis (August 23, 2021)
81 SER-287 for Ulcerative Colitis (July 22, 2021)
83 ABX464 for Ulcerative Colitis (May 24, 2021)
85 Jyseleca for Ulcerative Colitis (March 4, 2021)
87 Rinvoq for Ulcerative Colitis (February 22, 2021)
88 SHR0302 for Ulcerative Colitis (February 4, 2021)
90 AJM300 for Ulcerative Colitis (January 13, 2021)
91 Omilancor for Ulcerative Colitis (January 4, 2021)
93 Jyseleca for Ulcerative Colitis (December 15, 2020)
94 Rinvoq for Ulcerative Colitis (December 9, 2020)
95 Jyseleca for Ulcerative Colitis (October 12, 2020)
97 Etrolizumab for Ulcerative Colitis (October 11, 2020)
99 Zeposia for Ulcerative Colitis (October 10, 2020)
100 Etrolizumab for Ulcerative Colitis (August 9, 2020)
102 Etrolizumab for Ulcerative Colitis (August 9, 2020)
103 Zeposia for Ulcerative Colitis (June 2, 2020)
105 Jyseleca for Ulcerative Colitis (May 20, 2020)
107 Neihulizumab for Ulcerative Colitis (May 4, 2020)
109 KEY UPCOMING EVENTS
110 KEY OPINION LEADER INSIGHTS
111 UNMET NEEDS
111 Treatments that improve the natural history of UC
111 Effective, well-tolerated treatments that induce rapid and sustained remission
111 There is critical unmet need for predictive biomarkers
112 Novel oral treatments
113 BIBLIOGRAPHY
114 APPENDIX
LIST OF FIGURES
10 Figure 1: Ulcerative colitis disease extent
30 Figure 2: Trends in prevalent cases of ulcerative colitis, 2018–27
39 Figure 3: Overview of pipeline drugs for ulcerative colitis in the US
39 Figure 4: Pipeline drugs for ulcerative colitis, by company
40 Figure 5: Pipeline drugs for ulcerative colitis, by drug type
40 Figure 6: Pipeline drugs for ulcerative colitis, by classification
52 Figure 7: Probability of success in the ulcerative colitis pipeline
55 Figure 8: Clinical trials in ulcerative colitis
55 Figure 9: Top 10 drugs for clinical trials in ulcerative colitis
56 Figure 10: Top 10 companies for clinical trials in ulcerative colitis
56 Figure 11: Trial locations in ulcerative colitis
57 Figure 12: Ulcerative colitis trials status
58 Figure 13: Ulcerative colitis trials sponsors, by phase
63 Figure 14: Datamonitor Healthcare’s drug assessment summary for ulcerative colitis
69 Figure 15: Market dynamics in ulcerative colitis
70 Figure 16: Future trends in ulcerative colitis
81 Figure 17: TD-1473 for Ulcerative Colitis (August 23, 2021): Phase IIb/III – RHEA
83 Figure 18: SER-287 for Ulcerative Colitis (July 22, 2021): Phase IIb – ECO-RESET
85 Figure 19: ABX464 for Ulcerative Colitis (May 24, 2021): Phase IIb – Multiple Dose (103)
87 Figure 20: Jyseleca for Ulcerative Colitis (March 4, 2021): Phase II – MANTA
88 Figure 21: Rinvoq for Ulcerative Colitis (February 22, 2021): Phase III – U-Accomplish
90 Figure 22: SHR0302 for Ulcerative Colitis (February 4, 2021): Phase II – AMBER2
91 Figure 23: AJM300 for Ulcerative Colitis (January 13, 2021): Phase III – AJM300/CT3 (Japan)
93 Figure 24: Omilancor for Ulcerative Colitis (January 4, 2021): Phase II – Mild to Moderate UC
95 Figure 25: Rinvoq for Ulcerative Colitis (December 9, 2020): Phase IIb/III – U-ACHIEVE
97 Figure 26: Jyseleca for Ulcerative Colitis (October 12, 2020): Phase IIb/III – SELECTION
99 Figure 27: Etrolizumab for Ulcerative Colitis (October 11, 2020): Phase III – GARDENIA (vs. Infliximab; Sustained remission study)
102 Figure 28: Etrolizumab for Ulcerative Colitis (August 9, 2020): Phase III – HICKORY (TNF Intolerant)
103 Figure 29: Etrolizumab for Ulcerative Colitis (August 9, 2020): Phase III – HIBISCUS I (vs. Adalimumab; TNF Naive; Induction), Phase III – HIBISCUS II (vs. Adalimumab; TNF Naive; Induction), Phase III – LAUREL (TNF Naive/Refractory; Maintenance)
105 Figure 30: Zeposia for Ulcerative Colitis (June 2, 2020): Phase III – TRUE NORTH
107 Figure 31: Jyseleca for Ulcerative Colitis (May 20, 2020): Phase IIb/III – SELECTION
108 Figure 32: Neihulizumab for Ulcerative Colitis (May 4, 2020): Phase II – Proof of Principle
109 Figure 33: Key upcoming events in ulcerative colitis
LIST OF TABLES
11 Table 1: American College of Gastroenterology ulcerative colitis activity index
13 Table 2: 2019 ACG recommendations for induction of remission in patients with mildly active UC
14 Table 3: 2019 ACG recommendations for maintenance of remission in patients with previously mildly active UC
15 Table 4: 2019 ACG recommendations for induction of remission in patients with moderately to severely active UC
16 Table 5: 2019 ACG recommendations for maintenance of remission in patients with previously moderately to severely active UC
17 Table 6: 2019 ACG recommendations for hospitalized patients with acute severe UC
18 Table 7: 2017 ECCO treatment guidelines for proctitis
19 Table 8: 2017 ECCO treatment guidelines for left-sided UC
20 Table 9: 2017 ECCO treatment guidelines for extensive UC
21 Table 10: 2017 ECCO treatment guidelines for severe UC
22 Table 11: 2017 ECCO treatment guidelines for maintenance of remission
23 Table 12: 2019 NICE treatment guidelines for induction of remission in mild-to-moderate proctitis
24 Table 13: 2019 NICE treatment guidelines for induction of remission in mild-to-moderate proctosigmoiditis and left-sided UC
24 Table 14: 2019 NICE treatment guidelines for induction of remission in mild-to-moderate extensive UC
25 Table 15: 2019 NICE treatment guidelines regarding biologics and JAK inhibitors for moderate-severely active UC for all extents of disease
26 Table 16: 2019 NICE treatment guidelines for acute severe UC for all extents of disease
27 Table 17: 2019 NICE treatment guidelines for maintaining remission
29 Table 18: Prevalent cases of ulcerative colitis, 2018–27
32 Table 19: Marketed drugs for ulcerative colitis
41 Table 20: Pipeline drugs for ulcerative colitis in the US
73 Table 21: Historical global sales, by drug ($m), 2016–20
76 Table 22: Forecasted global sales, by drug ($m), 2021–25
78 Table 23: Multiple Drugs for Ulcerative Colitis (September 1, 2021)
80 Table 24: TD-1473 for Ulcerative Colitis (August 23, 2021)
82 Table 25: SER-287 for Ulcerative Colitis (July 22, 2021)
83 Table 26: ABX464 for Ulcerative Colitis (May 24, 2021)
86 Table 27: Jyseleca for Ulcerative Colitis (March 4, 2021)
87 Table 28: Rinvoq for Ulcerative Colitis (February 22, 2021)
89 Table 29: SHR0302 for Ulcerative Colitis (February 4, 2021)
90 Table 30: AJM300 for Ulcerative Colitis (January 13, 2021)
92 Table 31: Omilancor for Ulcerative Colitis (January 4, 2021)
93 Table 32: Jyseleca for Ulcerative Colitis (December 15, 2020)
94 Table 33: Rinvoq for Ulcerative Colitis (December 9, 2020)
96 Table 34: Jyseleca for Ulcerative Colitis (October 12, 2020)
98 Table 35: Etrolizumab for Ulcerative Colitis (October 11, 2020)
100 Table 36: Zeposia for Ulcerative Colitis (October 10, 2020)
101 Table 37: Etrolizumab for Ulcerative Colitis (August 9, 2020)
102 Table 38: Etrolizumab for Ulcerative Colitis (August 9, 2020)
104 Table 39: Zeposia for Ulcerative Colitis (June 2, 2020)
106 Table 40: Jyseleca for Ulcerative Colitis (May 20, 2020)
107 Table 41: Neihulizumab for Ulcerative Colitis (May 4, 2020)
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