This one is for my sister, who studies this stuff and is very interested in this drug!
In the world of Celiac research, there are currently about 14 drugs in or approaching clinical trials. It is literally a race to see which drug gets approved first! Each company uses a different method to attack the problem. There seems to be two large categories for solving the problem. First, degrade the gluten before it can do any damage or second, adjust the way the body reacts to the gluten.
Degrading the gluten before it does any damage should be a great idea for those who don’t want to affect the way their system works. This is a great option. Stop the damage before it starts. Schar removed the gluten before they make their products. They are also talking about removing gluten entirely when growing the wheat grain. All really interesting options. But that is not today’s topic.
Adjusting the way the body reacts to gluten is probably where most of the drugs are being worked on. AMG714 is on the table for discussion today.
Here’s the basic science to this. I’m sure much smarter people understand a lot more about this than I do, so please feel free to chime in. Interleukin 15 (IL-15) is one of the pro-inflammatory cytokines in the small intestine. It causes the the disruption in the “intestinal immune homeostasis” or it messes up your normal intestinal functioning. The scientists have done studies where they blocked this IL15 in genetically disposed mice to celiac disease on a gluten containing diet. They found the mice were able to eat a gluten containing diet without damage to the intestinal mucosa. Good for mice, right!!
Amgen has completed two Phase 2 studies. One study was where people took the drug once every two weeks for 12 weeks with biopsies at the beginning and end. There was a 10 week gluten challenge involved as well. Some were give high doses of gluten and some were given low doses of gluten. The results were presented at Digestive Diseases Week 2018 and they said, ”
While AMG 714 did not fully prevent gluten-induced mucosal injury in the gluten challenge group, the primary endpoint of the study, a decrease in intestinal inflammation was observed, as well as a non-significant trend towards reduced intestinal damage in the non-challenge group.” Again, a reduction in symptoms but still mucosal damage.
The second study was very similar but done on patients with Type 2 Refractory Celiac Disease. (I’ll explain that in a minute.) The end assessment for that study is whether or not they were able to reduce the number of abherrent (broken) aberrant small bowel intestinal intraepithelial lymphocytes. This study just completed in . But there is something interesting below….
Couple of side notes here. First, one of the diagnostic criteria for Celiac disease is an “increased number of intraepithelial lymphocytes”. In other words, intraepithelial lymphocytes act as the barrier between your intestine and the rest of your body. If there are increased intraepithelial lymphocytes, that means you have more than the normal amount and that is bad!
Second, there are different versions of Celiac disease. Celiac that responds to a gluten free diet – your gut heals on a gluten free diet and all is right with the world. This is the kind most people have.
But sometimes, very rarely, the gut doesn’t heal on a gluten free diet. Most of the time, doctors tell you that you are still eating gluten. But sometimes that isn’t the case. There is Refractory Celiac Disease Type 1 and Type 2 based on the number of abnormal intraepithelial lyphocytes in your biopsy – greater than 20% and you have Refractory Celiac Disease Type 2 (RCD2). Often RCD2, leads to lymphoma or the dreaded Celiac Cancer.
AMG 714 is hard to find information about. I had to dig and to know what I was looking for. Just a general search for AMG714 was not fruitful. I found lots of information about the companies that own it, but not much about the drug itself.
Here’s some company information. Provention has offered to fund Amgen’s Phase 2b trial in exchange for $150m payment at the successful end of 2b trials and “additional regulatory milestone payments and royalties if Amgen continues AMG 714 development.” So another company is basically financing Phase 2b studies in order to get a royalty once the drug is approved.
I cannot find if this drug has Fast Track designation at the FDA like some of its competitors in this race for Celiac drug.
As I’m doing research on these companies and drug trials, I’m finding many of them prevent or minimize symptoms due to accidental gluten exposure but do not protect against mucosal damage. Maybe that will be the first step on the road to a cure. Maybe that will be all we get and we have to decide if that is good enough. I’m not sure where this will end up and I keep changing my mind on whether symptom relief is good enough.
Ask questions if you need to. This was a complicated article to write because the information was difficult and hard to come by. Let me know if I didn’t make something clear. Also, I know there are some medical professionals out there reading. Please let me know if I made a mistake. I try, but I don’t have medical training and might make mistakes, so correct me if I’m wrong.
Article describing Interleukin 15’s role in Celiac.
Study results from Digestive Week 2018.
Article talking about the business of Provention and Amgen.