Monday, September 18, 2017

Possible Cures for Type-1 in the News (September)

Catching Up With NNC0114­-0006 (Anti IL-21)

Back in 2015 Novo-Norsk started a clinical trial into a combo treatment of NNC0114-0006 and Liraglutide (which is more commonly known as Victoza).  I ignored this trial, because I thought that NNC0114-0006 was a new form of insulin, and they were testing a treatment for type-1 diabetes. However, I have since found out that NNC0114-0006 targets IL-21 and that Liraglutide may stimulate beta cell growth.  Therefore, this combination could have the effect of stopping the autoimmune attack while at the same time regrowing beta cells, and that would be a path to a cure.

Liraglutide is approved for use in type-2 diabetes and works by increasing insulin production. Recently, experiments in mice have suggested that it works (at least partly) by helping the body grow more beta cells, and preventing the death of beta cells:

NNC0114-0006 is an anti IL-21 treatment.  IL-21 is a chemical that the immune system uses for communication, and several experiments have suggested that too much IL-21 is important to creating type-1 diabetes:
(and there are many more such studies.)

So combining these two treatments provides a possible path to a cure.

The Current Study

The study that started in 2015 is a phase-II? trial (the question mark means that it is a phase-II trial, but there has never been a phase-I trial for this combination of treatments).  The basic study design is four groups: one group gets both treatments, one group gets two placebos, one group gets NNC0114-0006 and placebo, and one group gets Liraglutide and a placebo.  So they have all their bases covered. The study is large: 304 people recruited from 100+ sites all over the US and Europe.

The clinical trial record says that this study is recruiting patients.  However, when I look at the list of locations, every one is marked "Active, not recruiting", "Completed", or "Suspended", so I'm very hopeful that they have recruited all the patients that they need.  That is important, because they expect to collect data for 80 weeks.  Their target completion date is April 2019.

This is actually the fifth study of NNC0114­-0006.  You can see the list here:
The four previous studies were smaller (between 10 and 65 people), and were done on other autoimmune diseases: Rheumatoid Arthritis, Crohn's Disease, and Systemic Lupus Erythematosus.

Clinical Trial Registry:
Other Study ID Numbers: NN9828-4150
2014-001215-39 ( EudraCT Number )
U1111-1154-7172 ( Other Identifier: WHO )
REec-2015-1768 ( Registry Identifier: Spanish registry )

Metreleptin Fails A Phase-I Trial

Back in the 2008-2010 timeframe there was some hope that Leptin would cure type-1 diabetes, and a clinical trial was started in 2010.  Then in 2015 the trial was canceled by one of the sponsors.  Finally, now in 2017 the results have been published, and the conclusions are:
Metreleptin is safe but may not be efficacious in improving glycemic control in patients with T1DM, although it reduces body weight and daily insulin dose modestly.
You can read my previous blogging here:
The abstract is here:
Clinical Trial Record:

Interesting Treatment for Multiple Sclerosis

I usually do not blog on cures or treatments for other diseases.  However, MS, type-1 diabetes and several other diseases are all from the same family of "autoimmune diseases".  They are all caused by the body's immune system attacking a different organ or internal system.  So in theory, research into curing one of these diseases might help cure the others.

So with that in mind, I thought this study was interesting:
Multiple Sclerosis Therapy NKTR-358 Begins Phase 1 Clinical Trial:

Basically, this company has a treatment which causes a person to generate more Treg cells.  Since Treg cells regulate the immune system, having more of them might prevent the immune system from attacking the wrong cells.  In type-1 diabetes, we have several research programs aimed at increasing Treg counts, but usually by growing more Tregs outside the body, and then infusing them into the body (T-Rex, Stem Cell Educator, and Stem Cells of Arabia are all working on similar ideas). NKTR-358 is a treatment which (they hope) will cause the body to generate more Treg cells, itself.

Also, NKTR-358 works at least partially, by targeting the IL-2 receptor in the immune system, and this receptor is also an active target of research in type-1:
(and the IL-2 targeted by NKTR-358 is different than the IL-21 targeted by NNC0114-0006 above.)

Company Information:
Some animal data:

Joshua Levy 
publicjoshualevy at gmail dot com 
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

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