/ inflammatory bowel disease

New treatments for inflammatory bowel disease (IBD) in clinical trials

Advances in our understanding of Crohn’s disease and ulcerative colitis have led to research that explores new pathways for treating inflammatory bowel disease (IBD). While these new treatments do not represent a cure for IBD, here are some of the notable new types of therapies, including biologics, small molecules, and stem cell infusions, that are being evaluated in clinical trials.

1. Small molecules

A small molecule is an organic compound that has a low molecular weight. Biologic drugs (such as Humira) are made by living cells, which are typically about 500-1000 times larger than small molecule inhibitors.

In the past, IBD was primarily treated by using small molecules such as prednisone, budesonide, and mesalamine, coupled with small molecule immunosuppressive treatments such as azathioprine, 6-MP, and methotrexate. Before Remicade (infliximab) was approved in 1998, the treatment of IBD was entirely based on small molecules. Since then, nearly all new medications approved for IBD have been biologics.

Compared to biologics:

  • Small molecule therapies are usually tablets taken orally, rather than given by injection.
  • You will not form antibodies against small molecule treatments due to the fact that they are not proteins.

New small molecule treatments in studies include:

  • Various JAK inhibitors. Tofacitinib, a JAK inhibitor, was approved for treating moderate to severe UC in May 2018. Other JAK inhibitors are currently in trials for both UC and CD.
  • Filgotinib, which had phase 3 programs in Crohn's disease and ulcerative colitis started in 2016.
  • Upadacitinib, which is in phase 3 trials for patients with Ulcerative Colitis and Crohn's disease.

2. S1P receptor modulators

Sphingosine-1-phosphate (S1P) receptor modulators are a class of drugs used as immunomodulators. Today, the only one available on the market is fingolimod, a treatment for multiple sclerosis.

Here are some S1P receptor modulators currently being evaluated in clinical trials:

  • Ozanimod, which has been shown to be fairly effective in phase 2 trials, is currently in a phase 3 study for Ulcerative Colitis. A phase 3 study evaluating Ozanimod for Crohn's Disease is planned to start in 2018.
  • Etrasimod (APD334) in a phase 2 trial for UC.

3. Anti-IL-23 biologics

Interleukins (ILs) are a group of cytokines (which are secreted proteins and signal molecules). How well the immune system can function is influenced by interleukins, and many new treatments being developed for autoimmune conditions are now based around targeting specific ILs. There are more than 50 different interleukins and related proteins.

Before IL-23 was discovered, IL-12 was being evaluated for its role in controlling inflammation. However, a study in a mouse model of multiple sclerosis showed that IL-23 was actually responsible for the inflammation, not IL-12. Since then, IL-23 has been shown to influence development of inflammation in numerous other areas where we previously thought IL-12 was responsible, including in arthritis, Crohn's Disease, Ulcerative Colitis, and psoriasis.

A review found that they are potentially more effective and safer than anti-IL-12/23 treatments.

Anti-IL-23 drugs currently being studied for IBD:

  • Risankizumab, which is currently in phase 3 trials for Crohn's Disease and Ulcerative Colitis.
  • Guselkumab, in a phase 2/3 study for Crohn's Disease.
  • Mirikizumab (LY3074828) from Eli Lilly, which is currently in its phase 3 trial for UC and a phase 2 study for Crohn's.

4. Gut specific anti-adhesion drugs

Gut specific anti-adhesion drugs work to block the movement of white blood cells into the GI tract, which helps control the symptoms of IBD. Because these therapies target the gut locally, they have the potential advantage of effectively treating Crohn's Disease and Ulcerative Colitis without weakening the rest of the body’s immune system. This appears to lead to lower risk of infections (such as pneumonia) outside of the bowel compared to other treatments.

Vedolizumab (Entyvio) is a gut-specific therapy administered intravenously that was approved by the FDA in 2014 for treating moderate-to-severe ulcerative colitis and Crohn's disease.

Other treatments that work similarly to Entyvio, but are subcutaneous injections (as opposed to intravenous) are currently in clinical trials.

Some of these new gut specific anti-adhesion drugs include:

  • Etrolizumab, an anti-integrin treatment that had positive results from its phase 2 trial and is currently in phase 3 testing for both Crohn's Disease and Ulcerative Colitis.

  • SHP-647 (Formerly owned by Pfizer and known as PF-0547659), is an anti-MadCam 1 biologic that had positive results from the phase 2 clinical trials run, and is currently in phase 3 testing for both Crohn's Disease and Ulcerative Colitis.

5. Stem cell therapies

Stem cell therapies being evaluated for IBD include hematopoietic stem cell transplantation (HCT), mesenchymal stromal cell infusions (MSC), and local MSC injections for perianal fistulas. Hematopoietic cells and mesenchymal cells have the ability to differentiate into a variety of cells, and act by potentially resetting the body’s immune system or filling in/closing fistulas.

These therapies have typically only been used for the most severe forms of Crohn’s disease or fistulizing Crohn’s disease. Although stem cell therapies show promising results, there is also the potential for side effects, such as a high rate of infections. Further studies are evaluating the benefits and risks of stem cell therapies in various different cases, including as a standalone treatment, and in combination with other drugs.

A study of stem cell injections for perianal fistulas (Alofisel/Cx601) sponsored by TiGenix and Takeda, is now opening at centers in the US.


Are you or a loved one interested in exploring new treatments for IBD being evaluated in clinical trials? Let us know! We'll help you every step of the way. Sign up for Clara now or follow this link to learn more about how Clara supports patients through the clinical trials process.

Peter Higgins, M.D.

Peter Higgins, M.D.

Dr. Peter Higgins, M.D., Ph.D, M.Sc. is the director of the Inflammatory Bowel Disease (IBD) program at the University of Michigan. He received his bachelor's and medical degree from Duke University.

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