Celgene Corporation is giving up on GED-0301 as a Crohn’s disease therapy, but will continue to evaluate its ability to treat ulcerative colitis.
It ended its Phase 3 REVOLVE clinical trial (NCT02596893) and its SUSTAIN extension trial (NCT02641392) of GED-0301 as a potential Crohn’s treatment after an independent trial monitoring board recommended the discontinuations. The board had reviewed the therapy’s benefits and risks, and the implication of its recommendation was that GED-0301 failed to generate enough benefits.
The review board recommendation prompted Celgene to cancel its plans for the Phase 3 DEFINE trial (NCT02974322), which was also supposed to evaluate GED-0301 as a Crohn’s therapy.
Celgene will continue testing GED-0301 as an ulcerative colitis therapy in a Phase 2 trial (NCT02601300) and other treatments it has developed for Crohn’s.
GED-0301 decreases levels of Smad7 in the gut. Excessive amounts of the protein interfere with the activity of a cytokine that immune cells release. Crimping the activity of the molecule, known as transforming growth factor beta 1 (TGF-β1), leads to inflammation.
“We thank the patients and the investigators involved in the REVOLVE trial,” Scott Smith, Celgene’s president and chief operating officer, said in a press release. Crohn’s “is a debilitating condition with few effective long-term treatment options. While we are disappointed with the results of REVOLVE, we remain committed to advancing our portfolio of novel medicines for patients suffering from this disease and other inflammatory bowel disorders.”
The company updated findings on its potential Crohn’s therapy ozanimod (RPC1063) at the World Congress of Gastroenterology in Orlando, Florida, Oct. 13-18. The presentations covered results from the Phase 2 TOUCHSTONE (NCT01647516) and STEPSTONE trials.
Celegene continues to evaluate ozanimod in the ongoing Phase 3 TRUENORTH trial (NCT02435992) and plans a Phase 3 pivotal trial of the therapy in Crohn’s in the next few months.
Ozanimod binds to two protein receptors — sphingosine 1-phosphate 1 (S1PR1) and sphingosine 1-phosphate 5 (S1PR5). Celegene believes the binding reduces the blood levels of a type of immune cell known as a lymphocyte and prevents lymphocytes from migrating to sites of inflammation. The combined effect reduces inflammation, the company believes.
In addition to developing ozanimod for Crohn’s and ulcerative colitis, Celgene is developing it as a possible treatment for relapsing multiple sclerosis.
Celgene is also conducting a Phase 2 trial of another therapy candidate, Otezla (apremilast), as a Crohn’s treatment. It expects results by the end of 2017. If they are promising, it is likely to start a Phase 3 trial program in 2018.
Otezla is a small-molecule inhibitor of the enzyme phosphodiesterase 4 (PDE4), which is associated with Crohn’s. Celgene believes Otezla regulates the production of inflammatory agents, but the company’s scientists have yet to determine how.
The U.S. Food and Drug Administration has approved Otezla as a treatment for moderate to severe plaque psoriasis and for adults with active psoriatic arthritis.