Significant opportunity remains for therapies to treat moderate to severe ulcerative colitis (UC), particularly for drugs with novel mechanisms of action that more effectively elicit mucosal healing, maintain and sustain long-term disease remission, and improve patients’ quality of life relative to the leading TNF-? inhibitor, infliximab. Current therapies for moderate to severe UC are associated with insufficient efficacy, sometimes serious safety concerns, and a high burden of delivery. Given that the cell adhesion molecule (CAM) inhibitor vedolizumab (Takeda’s Entyvio) recently launched and the oral Janus-activated kinase (Jak) inhibitor tofacitinib (Pfizer’s Xeljanz) is in late-stage development for UC, the competition in the TNF-refractory space is intensifying as companies try to differentiate their novel therapies and capture market share.
Questions Answered in This Report:
- Maintenance of remission, sustained remission, and improvement in quality of life are key goals in UC treatment. What are the key primary and secondary clinical trial end points on which new therapies are evaluated? How do U.S. and European gastroenterologists weigh specific efficacy end points and other drug attributes in their prescribing decisions for moderate to severe UC?
- Improved mucosal healing, improved maintenance of remission, improved sustained remission, and improved quality of life are key areas of unmet need in moderate to severe UC, according to the insights of surveyed U.S. and European gastroenterologists. Which therapies in development for moderate to severe UC are poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome to capitalize on these areas of unmet need? What degree of improvement over currently available therapies do surveyed U.S. MCO PDs seek from new therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?
- Effect on induction of clinical remission and a therapy’s incidence of serious, life-threatening effects (e.g., serious/opportunistic infections, malignancy) are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for moderate to severe UC. What trade-offs across these and other clinical attributes are U.S. gastroenterologists willing to make when considering prescribing a new therapy for moderate to severe UC? Based on these trade-offs, how do physician preference and prescribing likelihood vary across different product profiles for moderate to severe UC?
- By 2018, we expect, vedolizumab (Takeda’s Entyvio) will replace infliximab (Janssen/Merck/Mitsubishi Tanabe’s Remicade) as the gold-standard therapy in our Drug Comparator Model because of its superior clinical profile over the key current therapies we evaluated. On what clinical attributes is vedolizumab most differentiated from its competitors? Which other current therapies are at greatest risk of being replaced by vedolizumab?
Attributes included in conjoint analysis-based assessment of target product profiles for moderate to severe UC:
- Effect on induction of clinical remission at eight weeks.
- Effect on maintenance of clinical remission at 54 weeks.
- Effect on mucosal healing at 54 weeks.
- Incidence of serious, life-threatening effects (e.g., serious/opportunistic infections, malignancy).
- Immunogenicity (percentage of patients developing antibodies to the drug).
- Delivery burden (dosing formulation and frequency).
- Price/day (UC maintenance setting).
Attributes included in assessment of U.S. payers’ receptivity to new therapies for moderate to severe UC:
- Effect on induction of remission.
- Effect on maintenance of remission.
- Risk of serious/opportunistic infections.
- Burden of delivery (dosage formulation and dosing frequency).
Physicians surveyed: 63 U.S. and 33 European gastroenterologists.
Payers surveyed: 20 U.S. MCO PDs.
Comprehensive List of Therapies Included in Our Research and Modeling:
- Infliximab (Janssen/Merck/Mitsubishi Tanabe’s Remicade)
- Azathioprine (GlaxoSmithKline/Prometheus Laboratories/UCB’s Imuran, Eisai’s Imurek, generics)
- Adalimumab (AbbVie/Eisai’s Humira)
- Golimumab (Janssen/Merck/Mitsubishi Tanabe’s Simponi)
- Vedolizumab (Takeda’s Entyvio)
- Tofacitinib (Pfizer’s Xeljanz)
- Etrolizumab (Genentech/Roche)
- Eldelumab (Bristol-Myers Squibb)
- AJM-300 (Ajinomoto Pharmaceuticals)