Ulcerative Colitis / Crohn’s

Thought Leader Panel #20 2015-11

Therapeutic Area: Inflammatory Bowel Disease

Disease Area(s): Crohn’s disease, Ulcerative Colitis

Specialty/Location: Gastroenterology / N. America, Europe

Publication Date: November 2015

Principal Authors: Tricia L. Hanlon; Jeff Berk

Product Code: Gastro-20-2015-11

Abstract

Ulcerative Colitis/Crohn’s TLP #20 2015-11 summarizes a series of thought leader interviews that were conducted in October 2015. For this panel, BOLT / MedPredict spoke with 6 internationally recognized experts in the treatment of inflammatory bowel disease. The purpose of this Panel was to identify the events that will reshape the IBD landscape in 2016/2017. Thought Leaders offered their perspectives on the significance of the approval of vedolizumab for Crohn’s and ulcerative colitis, TNF biosimilars, next-generation anti-integrins, JAK inhibitors, IL23 inhibitors, S1P agonists, SMAD7 inhibitors, IL-6 inhibitors and a variety of therapeutic approaches that are in earlier clinical / preclinical development.

The Panel offers insight in the following areas:

• Anti-TNF positioning and sequencing in light of the vedolizumab approval.
• IL-23 +/- IL-12: Stelara in treatment experienced Crohn’s. Role for IL-23 selective inhibitors.
• JAK: Xeljanz infection risk in IBD.
• Other Mechanisms
• SMAD7
• S1P
• NK inhibition
• IL-6
• IL22
• TLR-9
• GPR84
• IL10
• ATPase
• Stem Cells
• RORγt
• other

The Panel specifically elaborates on the following Key Findings:

• The IBD category will see two new approvals in 2016.

• Ustekinumab will garner an approval in the US and EU for Crohn’s disease, with ulcerative colitis following about a year later. The drug will be available in both an infusion for induction and, if the physician and patient desire, an injection for maintenance.

• Tofacitinib 10 mg b.i.d. will be approved on both sides of the pond for ulcerative colitis. It is probably a mistake to assume that the complete response letter to Pfizer regarding tofacitinib for psoriasis portends a negative judgment on the TOFA ulcerative colitis registration by either FDA or EMA.

• About 25% of vedolizumab scrips are being written for anti-TNF naive patients. The response time is very long vs anti-TNF therapy, so the major drivers for choosing vedolizumab before anti-TNF are 1) patient’s disease burden – lower supports vedo use upfront), 2) patient’s infection risk, 3) patient’s aversion to biologics that increase infection risk and 4) cost (in Europe, vedolizumab is much less expensive than branded anti-TNF therapy)

• Etrolizumab’s efficacy looks to be very similar to vedolizumab, in both ulcerative colitis, and the less well-studied Crohn’s population. The key product differentiation will be the dose form: vedolizumab is delivered as a 30 minute weight independent iv infusion. Etrolizumab is an injectable product. This Panel tends to see infusion as the better way to go, particularly in the Crohn’s population. However, vedo is a fixed dose, as opposed to e.g. infliximab which is weight based, and Panelists think the fixed dose limits their optimizing of a vedolizumab-based strategy.

• Biosimilar anti-TNF is non-inferior to the parent brand when used in anti-TNF naive patients, but is inferior when switching due to antibody cross reactivity. Strategies to price the biosimilars at 20% below brand are being met by price matching by the innovator.

• S1P agonists are more likely to have a long term therapeutic benefit than is mongersen.

• NK cell inhibition is probably associated with better outcomes in IBD than is NK cell sparing.