The FDA in late April approved the first treatment targeting a genetic cause of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The historic approval of the drug tofersen – now marketed by Cambridge, Massachusetts-based Biogen, Inc. under the brand name QALSODY – is the start of a new chapter for the ALS treatment in a story that began in San Diego with an epiphany about “cellular paper shredders” in the human body.
Following the discovery of the gene associated with ALS in 1993, Center for Neurologic Study Director Richard A. Smith, M.D. posited that reducing the amount of work the body’s natural mechanism for eliminating the “ill-formed” proteins associated with ALS could reduce or even delay the expression of the disease, which usually begins to show in people between the ages of 30 and 70.
“When you buy a paper shredder, it works pretty well with five pieces of paper, but after three or four years, you’re lucky if you can put two pieces of paper in it,” Smith said. “So I thought, ‘Well the cellular paper shredder isn’t working too well at 40 years old, 50 years old. Maybe we could reduce the amount of ‘paper’ it has to dispose of.’ What if we lowered the amount of protein, maybe the body might heal itself to some degree.”
Biogen’s Big Ionis Investment
The idea was further developed by Smith, UC San Diego Department of Cellular and Molecular Medicine Chair Don Cleveland, Ph.D. and Ionis Pharmaceuticals Chief Science Officer Frank Bennett, Ph.D. The Ionis-backed team initiated pre-clinical investigation into the use of new antisense drugs to treat neurological disorders, eventually leading to tofersen to treat ALS in adults who have a mutation in the so-called superoxide dismutase 1 (SOD1) gene.
In 2018, as part of $1 billion commitment to invest in Ionis’ antisense technologies, Biogen optioned to license tofersen, taking over global development, regulatory and commercialization activities and costs for the drug. Under the terms of the collaboration for tofersen, Ionis is eligible to receive nearly $110 million, which is comprised of a $35 million license fee received in 2018, up to $18 million in development milestone payments and up to $55 million in regulatory milestone payments.
In addition, Ionis is eligible to receive tiered royalties up to the mid-teens on net sales from any antisense medicines developed under this collaboration.
In addition to tofersen, Biogen’s collaboration with Ionis include other ALS and neurodegenerative indications for Ionis’ antisense technologies.
“Biogen has been steadfast in our commitment to pursuing treatments for ALS, and I want to thank the scientists as well as the entire ALS community who have all worked tirelessly to bring this first-of-its-kind treatment to people with SOD1-ALS,” said Christopher Viehbacher, president and CEO of Biogen. “We believe this important scientific advancement will further accelerate innovative drug development for ALS.”
Impact on ALS Community
The approval of Biogen’s tofersen drug QALSODY was supported by 12-month integrated results from two separate clinical trials published in The New England Journal of Medicine.
“I have observed the positive impact QALSODY has on slowing the progression of ALS in people with SOD1 mutations,” said Timothy Miller, M.D., Ph.D., principal investigator of the QALSODY clinical trials and co-director of the ALS Center at Washington University School of Medicine in St. Louis. “The FDA’s approval of QALSODY gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”
Following the FDA approval announcement, ALS Association Golden West Chapter Chief Operating Officer Sheri Strahl and Vice President of Care Services Audra Hindes released a statement thanking Biogen, Smith, Bennett and Cleveland “for their commitment to the development of antisense oligonucleotide (ASO) therapies” calling its approval “a monumental milestone.”
Ionis Pharmaceuticals, Inc.
CEO: Brett Monia
Stock: IONS (NASDAQ)
Revenue: FY2022: $587 million
Notable: In 2018, Ionis inked a $1 billion deal with Biogen to develop antisense drug candidates for a broad range of neurological diseases.
CEO: Christopher Viehbacher
Headquarters: Cambridge, Massachusetts
Stock: BIIB (NASDAQ)
Revenue: $10.2 billion
Notable: Biogen has pioneered medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments for Alzheimer’s disease.