Biogen and Ionis Expand Collaboration to Develop Therapy Candidates for Alzheimer’s, Other Neurological Diseases

Biogen and Ionis Pharmaceuticals are expanding their strategic collaboration through a new 10-year agreement to develop novel RNA-targeted therapy candidates for a broad range of neurological diseases, including Alzheimer’s disease.

This agreement builds on the collaboration that produced Spinraza (nusinersen), the first and only approved treatment for spinal muscular dystrophy (SMA), and capitalizes on Biogen’s expertise in neuroscience research and drug development and Ionis’ experience in developing ribonucleic acid (RNA) targeted therapies through its antisense technology.

The two companies will advance programs in disease areas including dementia, neuromuscular diseases, movement disorders, ophthalmology, neuropsychiatry, and others. Ionis will identify antisense therapy candidates while Biogen will lead non-clinical studies, clinical development, manufacturing, and commercialization.

“Due to the ability of antisense oligonucleotides to directly intervene at the genetic origin of disease, we believe this approach could have a higher probability of success than traditional modalities, with a potentially more efficient development path to more rapidly help patients who suffer from diseases with limited or no treatment options,” Michael Ehlers, MD, PhD, executive vice president of R&D at Biogen, said in a press release. “Our experience with antisense therapeutics makes us believe that they will be the preferred drug modality for numerous genetic diseases and targets of the nervous system,”

The development of various forms of dementia, including Alzheimer’s disease, may be linked to the build-up of a protein called “tau” within the brain. Recent findings suggest that antisense treatment may not only halt the formation of new tau protein, but also reduce its existing levels.

Antisense oligonucleotides are short synthetic strands of nucleic acids that can bind to RNA — the intermediate molecule between DNA and functional proteins. These oligonucleotide chains have the potential to not only reduce expression of mutant proteins, but also restore or modify protein expression.

It was only in 1998 that the first gene-silencing antisense therapy was approved in the United States, called Vitravene (fomivirsen), developed by Ionis when the company was known as Isis Pharmaceuticals. The approval of Vitravene was considered a breakthrough in antisense therapy. However, it took more than a decade for other antisense therapeutics to reach the U.S. market — the next would be the anti-cholesterol drug Kynamro (mipomersen) in 2013 and Exondys 51 (eteplirsen), for the treatment of Duchenne muscular dystrophy (DMD), in 2016. Spinraza followed closely.

Now, interest in using antisense oligomers to treat various forms of dementia is growing. Findings earlier this year revealed that antisense oligonucleotides administered to mouse and monkey models with tauopathy were able to decrease the levels of tau in the brain and cerebrospinal fluid, reverse preexisting tau pathology and seeding activity, and halt neuronal loss while extending survival.

“Our collaboration with Biogen has provided significant value for both companies. We have and continue to learn more about neurological diseases and successful strategies for developing drugs for these diseases,” said Dr. C. Frank Bennett, senior vice president of Research and Franchise Leader for the Neurological Programs at Ionis. “Biogen has worked with us to validate biomarkers and develop new clinical trial endpoints. Ionis has helped Biogen understand our antisense platform and the large potential of this powerful drug modality in neurological diseases.

“Looking ahead, we are focused on continuing to advance Ionis’ antisense technology and on creating an exciting stream of drugs for neurological diseases — both for Biogen and for our wholly-owned neurological disease portfolio,” Bennett said.

The companies expect the deal to close in the second quarter of 2018.