New trial will investigate improved ASO technology in people with ALS
Recently Biogen announced two new clinical research
projects in ALS. One of these is a clinical trial exploring a potential
investigational therapeutic (BIIB067/ISIS-SODRX)
for the SOD1 form of the disease, and the other will
explore potential outcome measures
for future use in all ALS clinical trials. Both trials are expected to open for
recruitment soon at centers in the US and abroad.
The investigational therapeutic clinical trial in ALS seeks
to determine the safety and tolerability of an antisense oligonucleotide (ASO) therapy in people with
ALS whom are also carriers of a mutation in the SOD1 gene. This trial builds on
previous work using ASO technology to target ALS and is being conducted in
partnership with Isis
Pharmaceuticals, a San Diego biotechnology company. Isis officially
announced the start of the trial December 11, 2015 with a press
The investigational therapeutic is designed to disrupt the
process by which the mutated SOD1 gene creates misfolded proteins. These abnormal
proteins and several different genes associated with ALS have been found to
produce similar products. Misfolded proteins cause cells such as motor neurons
significant cell stress. An abundance of misfolded proteins inside motor
neurons is thought to play a central role in the onset and progression of ALS.
This new clinical trial aims to halt the production of these misfolded proteins
in hope of slowing or stopping the disease altogether. The investigational therapy
will be delivered intrathecally to the spinal fluid. People with ALS enrolled
in this trial will be asked to provide samples of their spinal fluid
(cerebrospinal fluid, CSF) throughout the study which will allow the
researchers to measure changes in the levels of SOD-1 as a result of treatment.
This initial study is designed to determine the safety and tolerability of the
ASO treatment, an important first step before moving into efficacy studies.
This new Phase 1 study builds on previous work led by
Timothy Miller, Ph.D., M.D., using first generation ASO technology. This new
trial will enroll more people with ALS than the previous study, and the ASO
being evaluated has been improved upon. For example, the Generation 2.0 ASO has
been redesigned to better target the precursors to misfolded SOD1 protein and to
be delivered in a matter of minutes to the study participants, as opposed to
many hours with the earlier generation of therapy.
The study is officially called “Single and Multiple Dose
Study of BIIB067 (Isis-SOD1Rx) in Adults With Amyotrophic Lateral Sclerosis
(ALS).” Biogen and Isis Pharmaceuticals have organized a network of 18
enrollment centers in 9 countries to enroll as many as 72 people with ALS in
the project. This is a two-part study in which testing positive for the SOD1
gene is NOT a requirement to participate in the initial part of the trial. More
information about full inclusion criteria can be found online here.