Unfortunately, AMG714 was not the drug we were hoping for. AMG714 was in clinical trials for two reasons – first to help with those with RCD type 2 and the second was for normal gluten exposure. Unfortunately, neither had the desired outcome.

First the RCD type 2 results, but we have to define Refractory Celiac first.

Refractory Celiac Disease (RCD) has two types – type 1 and type 2. Refractory Celiac Disease is where a patient initially responds to the gluten free diet but after 6 to 12 months symptoms return and intestines don’t heal. The intraeptihelial lymphocytes (IEL) become abnormal and could be the beginning of cancer. The difference between RCD type 1 and RCD type 2 is the number of these abnormal IEL’s. If fewer than 20% of IEL’s are abnormal, RCD1 is diagnosed and about 1 in 100 celiac patients are diagnosed with RCD1. If more than 20%, RCD2 is diagnosed and about 1 in 200 are diagnosed with RCD2.

RCD1 is typically treated with steroids and close monitoring. RCD2 is the bad kind and is considered a cancer. RCD2 has a 5 year survival rate of 40%-58%, so not good. There is currently no standard of treatment for RCD2, so a drug is vital for those suffering with RCD2.

The AMG714 study for RCD2 enrolled 28 patients. They were given at least 7 intravenous doses of AMG714 over the course of 12 weeks. They were given endoscopies at the beginning and end of the study and did a gluten challenge. They found that abherrant IEL’s went down and Marsh scores didn’t change. However, 25 out of 28 enrolled patients, 8 on the placebo side and 17 on the drug side, had adverse events. Adverse events in clinical trial language means side effects.

In the second study, the one with celiac patients and gluten challenge the results were about the same. They enrolled 64 patients into three categories – 150mg AMG 714, 300mg AMG 714, and placebo. They state right in the middle of their results, “AMG 714 did not prevent mucosal injury due to gluten challenge.” Ugh. That hurts. But they did say that diarrhea in both drug categories did dissipate significantly. Unfortunately, everyone on all three arms experienced adverse events with the most common being injection site discomfort.

The hopeful thing at the end of the RCD2 study they say, “Effects on symptoms and other endpoints suggest that further research of AMG 714 may be warranted in patients with refractory coeliac disease type 2.” At the end of the gluten challenge study they say, ” Effects on intraepithelial lymphocyte density and symptoms suggest that further research of AMG 714 may be warranted in patients with non-responsive coeliac disease.” I didn’t get that from either study, but they may have seen something I didn’t. Maybe they are going to reformulate and retest. Maybe they saw something in one of the tests they ran they didn’t report on. I don’t know. We will have to wait and see.

The more I hear, the more I will let you know.