Share Facebook
Crohn's Disease Forum » Parents of Kids with IBD » Drugs in the pipeline


07-26-2016, 09:52 PM   #1
Maya142
Forum Monitor
 
Maya142's Avatar
 
Join Date: Jul 2013

My Support Groups:
Drugs in the pipeline

Always like to read about what's next!

The whole article is here: http://www.gastroenterologyandhepato...ase-treatment/

G&H Are there any promising anti-integrin drugs in the pipeline?

WS Etrolizumab (Genentech) is an interesting drug in the same general class as vedolizumab that is currently being tested in phase 3 trials in patients with ulcerative colitis as well as in patients with Crohn’s disease. Like vedolizumab, etrolizumab blocks alpha-4 beta-7, but it also blocks alpha-E beta-7, which affects lymphocyte trafficking to the skin and to the gut. Blocking alpha-4 beta-1 can lead to progressive multifocal leukoencephalopathy (PML), but both etrolizumab and vedolizumab do not impact lymphocyte trafficking to the brain, which is mediated vs alpha-4 beta-1 integrins. Thus, these 2 drugs are seen as brain-sparing and are not associated with PML.

G&H Which sphingosine-1-phosphate receptor modulators are currently under clinical investigation?

WS Sphingosine-1-phosphate (S1P1) receptor modulators lead to internalization of the S1P1 receptor, which is located on surface C-C chemokine receptor type 7–positive lymphocytes, resulting in an inability for these lymphocytes to follow the S1P1 gradient on the lymphatic endothelium, thus functionally trapping the lymphocytes in lymph nodes until they die.

One promising S1P1 receptor modulator is RPC1063, or ozanimod (Celgene). This drug was shown to be effective in a phase 2 trial in ulcerative colitis and is currently being tested in a phase 3 trial in ulcerative colitis and a phase 2 trial in Crohn’s disease. There are 2 other S1P1 modulators in development for patients with inflammatory bowel disease: APD334 (Arena Pharmaceuticals) and MT-1303 (Biogen Idec).

G&H Are there any promising agents that block interleukin-12 and/or -23?

WS Anti-P40 and anti-P19 antibodies block signaling through the Th1 and Th17 pathways. Ustekinumab (Stelara, Janssen) is an anti-P40 antibody that blocks the P40 subunit of interleukin (IL)-12 and -23. This agent is currently approved by the FDA for psoriasis and psoriatic arthritis and has finished phase 3 testing in Crohn’s disease. Clinical trial data have recently been presented in abstract form showing that ustekinumab is effective for induction of remission in patients with inflammatory bowel disease who are failing conventional therapy (not anti-TNF drugs) and separately for induction of remission in patients who have failed anti-TNF drugs. A maintenance trial mixed these 2 populations and showed that the drug is effective for maintaining remission for over a year. Ustekinumab is currently under review for FDA approval, and a decision is expected in the third quarter of this year.

A number of other drugs are being developed that have anti–IL-23 antibodies directed toward P19. LY-2525623 (Lilly) is being evaluated in a phase 2 trial in ulcerative colitis. Boehringer Ingelheim just partnered with AbbVie to develop BI 655066, an anti–IL-12 antibody that has been tested in Crohn’s disease and has positive phase 2 data. AstraZeneca MedImmune, in partnership with Amgen, has an anti-P19 antibody drug called AMG 139/MEDI2070. A phase 2 study in Crohn’s disease showed that this drug was able to achieve clinical remission and improve blood and stool biomarkers. Janssen is developing a drug for psoriasis comprised of an anti-P19 antibody to IL-23 (guselkumab) that could be tested in Crohn’s disease in the future.

G&H Which Janus kinase inhibitors show promise?

WS Janus kinase (JAK) inhibitors block a variety of proinflammatory cytokines by blocking the JAK/Signal Transducer and Activator of Transcription signaling pathway. Tofacitinib (Xeljanz, Pfizer), which is currently approved by the FDA for rheumatoid arthritis, is a small molecule that blocks predominantly JAK1 and JAK3 receptors but also has some JAK2 effects at higher doses. A phase 2 study showed that the drug was highly effective in ulcerative colitis, and two phase 3 studies recently showed that the drug was effective for inducing response, remission, and mucosal healing, both in patients with moderate to severe ulcerative colitis who are failing anti-TNF drugs as well as in patients who are naive to anti-TNF therapy. A phase 3 maintenance trial will be completed in the third quarter of this year, which means that tofacitinib may be sent for FDA review sometime next year.

In addition, ABT-494 (AbbVie), a JAK inhibitor that is more JAK1-selective, is being evaluated for both ulcerative colitis and Crohn’s disease. The JAK inhibitor filgotinib (GLPG0634, Galapagos and Gilead) has positive phase 2 data in Crohn’s disease and will undergo phase 3 testing in ulcerative colitis and Crohn’s disease.

G&H Are there any other promising inflammatory bowel disease agents in the pipeline?

WS A metalloproteinase-9 antibody (GS-5745, Gilead) showed some evidence of efficacy in a phase 1A study in ulcerative colitis and will be undergoing phase 2/3 trials in ulcerative colitis and Crohn’s disease.

The oral SMAD7 antisense oligonucleotide drug called mongersen (GED-0301, Celgene) showed significant evidence of efficacy for inducing clinical remission in Crohn’s disease. It is now in another phase 2 trial and will soon be in a phase 3 trial for Crohn’s disease.
__________________
Mom of M (20)
diagnosed with Crohn's Disease at 16
Juvenile Idiopathic Arthritis at 12
Juvenile Ankylosing Spondylitis at 16

Mom of S (23)
dx with JIA at 14
Ankylosing Spondylitis at 18
07-26-2016, 10:05 PM   #2
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
Love it !!!
__________________
DS - -Crohn's -Stelara -mtx-IVIG
07-26-2016, 10:29 PM   #3
Maya142
Forum Monitor
 
Maya142's Avatar
 
Join Date: Jul 2013

My Support Groups:
The IL 23 drugs (3 of them plus Stelara) and Tofacitnib (Xeljanz - already approved for RA) should also work for JSpA/AS .

We were told the Boehringer Ingelheim IL 23 drug is doing VERY well for both AS and Crohn's and is magic for Psoriasis!
07-28-2016, 10:23 AM   #4
Farmwife
Forum Monitor
 
Farmwife's Avatar
 
Join Date: Apr 2012
Location: Michigan

My Support Groups:
Thanks
__________________
I'm mom to............... Little Farm Girl 8 yr old
Ibd (microscopic)
(12/28/12),
dx Juvenile Arthritis
(12/13/13)
dx Erthema Nodosum
(8/13/14)
Bladder and Bowel Dysfunction
(10/14/13)
Ehlers-Danlos Syndrome dx (1/26/17)
Remicade started on (9/8/14)Every 4 wks
Azathroprine started on 10/9/15
EN/EEN- since (1/12/13)
Past Meds- LDN, Humira, Pred, MTX, Sulfasalazine
07-31-2016, 06:56 AM   #5
Optimistic
Senior Member
 
Optimistic's Avatar
 
Join Date: Oct 2014

My Support Groups:
Great!

Boehringer Ingelheim IL 23 is the one I'm hearing a lot about professionally. I posted and several forum members replied they didn't think there was anything good coming. I'm glad you found this article to give some detail. Let's hope...
07-31-2016, 02:24 PM   #6
Maya142
Forum Monitor
 
Maya142's Avatar
 
Join Date: Jul 2013

My Support Groups:
Any idea when that one would be approved Optimistic? Or is it not far enough in trials yet to be able to tell?
07-31-2016, 02:30 PM   #7
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
After 12 weeks, approximately twice as many patients with moderate-to-severe Crohn’s disease, the majority of whom had previously failed treatment with one or more TNF antagonists, achieved clinical remission with risankizumab compared with placebo1
Endoscopic remission was achieved in 15% and 20% of patients receiving 200 mg and 600 mg risankizumab, respectively, compared with three percent of patients receiving placebo after 12 weeks1
These results indicate that the selective blockade of IL-23 with risankizumab may be a promising new therapeutic approach for this serious chronic disease and warrants further investigation
Ingelheim, Germany, and North Chicago, Ill., 24 May 2016 –Results were presented today from a proof-of-concept, Phase II, randomized, placebo-controlled study (NCT02031276) in Crohn’s disease with investigational biologic, risankizumab (formerly BI 655066), a compound from Boehringer Ingelheim research and recently licensed by AbbVie. Risankizumab was shown to be more effective than placebo in patients with moderately-to-severely active Crohn’s disease.1 These interim results are the first to be reported in this indication with risankizumab, which selectively blocks IL-23 through the specific targeting of the IL-23p19 subunit.1 After 12 weeks, 24% and 37% of patients achieved clinical remission (no symptoms or very mild symptoms of disease) with 200 mg and 600 mg risankizumab, respectively, compared with 15% of patients receiving placebo*1. Endoscopic remission (normalization of the lining of bowel as seen during an endoscopy) was achieved by 15% and 20% of patients receiving 200 mg and 600 mg risankizumab, respectively, compared with three percent of patients receiving placebo.1

From
https://www.boehringer-ingelheim.com...oderate-severe


So phase II drug trials right now
But doing better than stelera for psoriasis
07-31-2016, 02:32 PM   #8
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
15 and 20% achieving endoscopic remission seems very very low to me
07-31-2016, 02:37 PM   #9
Maya142
Forum Monitor
 
Maya142's Avatar
 
Join Date: Jul 2013

My Support Groups:
It does seem low. We were told about this drug in 2015 though, so perhaps it's not doing as well as anticipated.

On the other hand, perhaps they are still trying to find the right dose?
07-31-2016, 02:55 PM   #10
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
They had 24 and 37% achieved clinical remission which seems about norm for a anti tnf but ....
Not sure what the other biologics numbers would be for histological remission kwim
08-01-2016, 04:56 PM   #11
Optimistic
Senior Member
 
Optimistic's Avatar
 
Join Date: Oct 2014

My Support Groups:
Any idea when that one would be approved Optimistic? Or is it not far enough in trials yet to be able to tell?
I think there is some later data that hasn't been published. I'll ask. Hang on!
11-25-2016, 11:08 AM   #12
xeridea
Senior Member
 
xeridea's Avatar
 
Join Date: Jul 2014

My Support Groups:
Updating something mentioned by Maya142 in the original post, Gilead has announced that they're terminating GS-5745 trials for CD and UC because preliminary data failed to show efficacy for either condition.
11-25-2016, 12:01 PM   #13
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
Separately, a Phase 3 study of GS-5745 is ongoing in patients with gastric cancer, as well as a Phase 2 study in patients with gastric cancer in combination with nivolumab and additional Phase 2 studies in moderately to severely active Crohn’s disease, rheumatoid arthritis and cystic fibrosis. These studies will continue as planned.
From link above

http://www.gilead.com/news/press-rel...rative-colitis

So still moving forward for crohns just not UC
11-25-2016, 03:41 PM   #14
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
http://www.tandfonline.com/doi/full/...X.2016.1112271

Future drugs and thoughts
Enjoy
01-17-2017, 02:48 PM   #15
willgare
 
willgare's Avatar
 
Join Date: Mar 2016
Location: Manchester UK

My Support Groups:
Mongersson is the one to look out for...

__________________
Diagnosis: Crohn's, 1999
Past Medication: Prednisone, Imuran, Infliximab
Current Medication: Vedolizumab (currently on loading doses)
Currently: In Steroid induced remission
Reply

Crohn's Disease Forum » Parents of Kids with IBD » Drugs in the pipeline
Thread Tools


All times are GMT -5. The time now is 10:19 PM.
Copyright 2006-2017 Crohnsforum.com