Tuesday, June 12, 2018
GNbAC1 Starts A Phase-II? Trial
GNbAC1 is a monoclonal antibody which has completed phase-II testing for treating Multiple Sclerosis, which (like type-1) is an autoimmune disease. GNbAC1 was developed by GeNeuro SA, a Swiss company, but is being tested in Australia. They have partnered with Servier, a large French pharma company to do the phase-III trials required to bring it to the Multiple Sclerosis market.
A monoclonal antibody is an artificially created antibody which targets one very specific type of cell in the body. Different monoclonal antibodies target different types of cells. So if a disease is caused by a problem in one type of cell, then using a monoclonal antibody to target that type of cell is a promising treatment. Because several monoclonal antibodies have been successful in treating other autoimmune diseases, they are an active area of research for curing type-1 diabetes.
Previously, GNbAC1 has been tested in four clinical trials as part of the Multiple Sclerosis development program, so its safety is well established (for an investigational drug). However, since this is the first trial aimed at type-1 diabetes, I'm calling it a "Phase-II?" trial. (The question mark meaning "no previous testing on people with type-1".)
This study has enrolled 60 people who were diagnosed with type-1 diabetes within the last 4 year. The first part will be double blind, with 2/3s getting the treatment and 1/3 not. After that will be a second, optional part which is not blinded (everyone will get the treatment). Unfortunately, the primary end point for this trial is safety related. But their press release does say that they will track various effectiveness outcomes as well (for example: C-peptide and insulin consumption). The drug will be given as an IV drip once a month (six doses in each part of the study). People in the study will be followed for about a year.
This study completed enrollment in January 2018, and GeNeuro plans to publish the results from the first part of the trial in September 2018, and the second part of the trial in the first half of 2019. That is pretty quick!
Press Release: http://www.geneuro.com/data/news/GeNeuro-TD1-Study-Enrollment-Complete.pdf
Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT03179423
General Background News Article: http://www.biotuesdays.com/features/2017/11/16/geneuro-pioneering-hervs-against-neurodegenerative-and-autoimmune-diseasess
Background and Rational
This clinical trial has a very different rational, as compared to previous attempts to cure type-1 with monoclonal antibodies. In the past, these antibodies have been used to target one of the defective cell types within the immune system. The idea is to find an immune cell which is involved in the attack on the beta cells, and kill off those immune cells. That idea has led to some progress, some suggestive results, but nothing like a cure.
These researchers have a different idea. They note that part of the human genome contains HERVs, which are the remains of retroviral DNA which merged into our DNA millions of years ago. The researchers believe that while this DNA does nothing most of the time, infection can sometimes cause one of these HERVs (called "pHERV-W") to activate and generate a protein (called "pHERV-W env") used by the retrovirus the DNA came from originally. Even after the infection, the HERV DNA stays activated. The pHERV-W env, in turn, causes autoimmune diseases. If true, this would explain how viral infections can "trigger" type-1 diabetes.
These researchers believe that by using a monoclonal antibody to target pHERV-W, they can stop this process. So while previous attempts to use monoclonal antibodies targeted malfunctioning immune cells, this attempt is targeting HERV DNA which (according to this theory) is the root cause of the autoimmunity.
Background reading: https://en.wikipedia.org/wiki/Endogenous_retrovirus
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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.