Ionis and Biogen Advance Second Drug for ALS into Clinical Development Under Broad Neurological Disease Collaboration

– Phase 1/2 study of IONIS-C9Rx initiated in patients with ALS with a C9ORF72 mutation, the most common genetic form of ALS –

Ionis reinforces leadership position in neurological disease with expanding clinical pipeline –

This week, along with our partner Biogen, we announced the initiation of the Phase 1/2 clinical study of IONIS-C9Rx (also known as BIIB078) in patients with Amyotrophic Lateral Sclerosis (ALS) who have a mutation in the chromosome 9 open reading frame 72 (C9ORF72) gene. The multi-ascending dose study will evaluate the safety, tolerability and pharmacokinetic profile of IONIS-C9Rx administered intrathecally as well as a variety of exploratory endpoints to determine the dose and refine the clinical endpoints for a future pivotal study.

IONIS-C9Rx represents a novel approach to treating ALS, a rare, fatal neurodegenerative disorder for which there is no cure. C9ORF72 mutation is the leading known genetic cause of ALS. IONIS-C9Rx is the second drug from our Biogen collaboration targeting a familial type of ALS. The first is IONIS-SOD1Rx (also known as BIIB067), designed to treat superoxide dismutase 1(SOD1)-related ALS, caused by a mutation in the SOD1 gene. We anticipate Phase 1/2 data for IONIS-SOD1Rx in the next 6 months.

ALS is an important and devastating disease with significant unmet medical need. ALS is characterized by the progressive degeneration and dysfunction of neurons in motor pathways, resulting in a declining quality of life. 1,2

We are committed to using our novel antisense technology to find a treatment for people with ALS by pursuing numerous targets associated with both familial and nonfamilial forms of the disease. The two drugs under our Biogen partnership are part of a much larger research effort focused on discovering and advancing novel treatments for ALS as well as other neurological diseases.

Our highly productive antisense platform has generated ten novel drugs for neurological diseases, eight of which are a result of our strategic partnership with Biogen. To date, the keystone accomplishment of our collaboration with Biogen is the blockbuster success of SPINRAZA® (nusinersen), the first and only approved treatment for patients with spinal muscular atrophy (SMA). In our Biogen collaboration we are also evaluating IONIS-MAPTRx in a Phase 1/2 study in patients with Alzheimer’s Disease and have three other exploratory programs (IONIS-BIIB6Rx, IONIS-BIIB7Rx and IONIS-BIIB8Rx) currently in IND-enabling toxicology studies.

Our extensive neurological disease pipeline also includes IONIS-HTTRx (RG6042), licensed to Roche, a potential treatment for people with Huntington’s Disease (HD). It is the first and only drug to demonstrate reduction of the mutant huntingtin protein, the underlying cause of HD. Roche is preparing to begin a pivotal study to evaluate IONIS-HTTRx in a larger number of patients to further characterize its safety and efficacy in adults with HD.

It is important to note that we are also independently advancing programs for Alexander Disease, Lafora Disease and Charcot-Marie-Tooth Disease, with plans to add several new drugs to our pipeline over the next 12-18 months. Most recently, our drug TEGSEDI was approved in Europe for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR). It is being commercialized by our affiliate Akcea. Also in collaboration with Akcea, we are developing AKCEA-TTR-LRx for the treatment of all forms of TTR amyloidosis, including both hereditary and wild-type cardiomyopathy.

For almost 30 years, our antisense drug discovery platform has served as a springboard for innovation and hope for patients with unmet needs. Ionis-discovered drugs have the potential to revolutionize the treatment of diseases – for neurology and beyond – and to transform the lives of patients and their families.


  1. Van Blitterswijk, M., DeJesus-Hernandez, M., & Rademakers, R. (2012). How do C9ORF72 repeat expansions cause ALS and FTD: can we learn from other non-coding repeat expansion disorders? Current Opinion in Neurology, 25(6), 689–700. (Link:
  2. McCampbell et al., “Antisense oligonucleotides extend survival and reverse decrement in muscle response in ALS models.” The Journal of Clinical Investigations, Advanced Online Publication, July 16, 2018 (Link: