Ionis Announces FDA Accepts New Drug Application and Grants Priority Review of Tofersen for Rare Genetic Form of ALS

  • SOD1-ALS is a rare genetic form of ALS that affects approximately 330 people in the United States, it is progressive, causes loss of daily functions and is uniformly fatal
  • If approved, tofersen would be the first treatment to target a genetic cause of ALS
  • The 12-month data included in the dossier show that early initiation of tofersen slowed the decline in measures of clinical and respiratory function, strength and quality of life; tofersen also resulted in robust and long-lasting reductions in neurofilament, a marker of neurodegeneration

CARLSBAD, Calif., July 26, 2022 /PRNewswire/ — Ionis Pharmaceutical products (Nasdaq: IONS) today announced that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (nes) for toferseninvestigation antisense medicine for the treatment of superoxide dismutase 1 amyotrophic lateral sclerosis (SOD1-ALS). The nes was submitted by biogenicwho authorized tofersen of Ionis in 2018. The application received priority review and was given an action date under the Prescription Drug User Fees Act of the January 25, 2023. The FDA noted that it currently plans to hold an advisory committee meeting for this application. The average life expectancy of people with ALS is three to five years from the time of onset of symptoms; patients with certain SOD1 mutations have an even shorter life expectancy. There is currently no targeted treatment for SOD1-ALS.

“Acceptance of the new drug application for tofersen is a monumental milestone, not only for Ionis but for all people with SOD1-ALS, their families and healthcare professionals who are battling this devastating disease. We express to them our deepest gratitude. Their courage was instrumental in achieving this goal,” said C. Frank Bennett, Ph.D., Executive Vice President, Chief Scientific Officer and Head of Franchise for Neurological Programs at Ionis. “We would also like to thank Biogen for its commitment to advancing tofersen, which, if approved, will be the first treatment targeting a genetic cause of ALS.” Dr. Bennett added: “The NDA acceptance for tofersen further strengthens Ionis’ platform strategy to more broadly target all forms of ALS and central nervous system disorders.

Biogen is seeking approval for tofersen under the FDA’s fast-track approval process, based on the use of neurofilament as a surrogate biomarker that is reasonably likely to predict clinical benefit. Neurofilaments are normal proteins found in healthy neurons, which are increased in blood and cerebrospinal fluid when damage has been done to neurons or their axons and are a marker of neurodegeneration. In ALS, higher levels of neurofilaments have been shown to predict faster decline in clinical function and shortened survival. The results of Tofersen’s study suggest that reductions in neurofilament preceded and predicted slower declines in measures of clinical and respiratory function, strength, and quality of life. Biogen has stated its commitment to generating ongoing data and finalizing the confirmation dossier with the FDA.

The tofersen NDA included results from a Phase 1 study in healthy volunteers, a Phase 1/2 study evaluating escalating dose levels, the Phase 3 VALOR study and the extension study open (OLE). Also included are the most recent 12-month integrated results from VALOR and the OLE study, recently presented at the annual meeting of the European Network for the Cure of ALS (ENCALS).

As reported in October 2021, VALOR, a six-month randomized Phase 3 study, did not meet the primary endpoint of change from baseline to week 28 in the Amyotrophic Lateral Sclerosis Revised Functional Rating Scale. However, trends of reduced disease progression on several secondary and exploratory endpoints were observed. Integrated 12-month VALOR and OLE data showed that early initiation of tofersen resulted in long-lasting reductions in neurofilament, a marker of neurodegeneration, and slowed decline across several efficacy parameters.

In the 12-month data, the most common adverse events (AEs) among participants receiving tofersen in the VALOR study and the OLE study were headache, procedural pain, falls, back pain, and extremity pain. Most AEs in VALOR and OLE were mild to moderate in intensity. Serious AEs were reported in 36.5% of participants who received tofersen in VALOR and/or OLE and 17.3% of participants discontinued treatment due to an AE.

During the FDA review period, Biogen will maintain its early access program for tofersen, which now has participants in more than a dozen countries. The open-label extension and the ATLAS phase 3 study in presymptomatic individuals carrying a SOD1 genetic mutation are still ongoing. Biogen is actively working with other regulators around the world and will provide updates as needed.

About Tofersen

Tofersen is an antisense drug being evaluated for the potential treatment of SOD1-ALS. Tofersen binds to SOD1 mRNA, allowing it to be degraded by RNase-H with the aim of reducing the synthesis of SOD1 protein production. In addition to the ongoing open-label expansion of VALOR, tofersen is being studied in the Phase 3 ATLAS study designed to assess whether tofersen can delay clinical onset when initiated in presymptomatic individuals with SOD1 genetic mutation and biomarker evidence of disease activity. Biogen has licensed tofersen from Ionis under a collaborative development and licensing agreement.

About Amyotrophic Lateral Sclerosis and SOD1-ALS

Amyotrophic lateral sclerosis (ALS) is a rare, progressive and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and spinal cord responsible for controlling voluntary muscle movement. People with ALS suffer from muscle weakness and atrophy, which causes them to lose their independence as they gradually lose the ability to move, talk, eat and eventually breathe. The average life expectancy for people with ALS is three to five years from the onset of symptoms. Patients with certain SOD1 mutations have an even shorter life expectancy.

Several genes have been implicated in ALS. Genetic testing helps determine if a person’s ALS is associated with a genetic mutation, even in people with no family history of the disease. Currently, there are no genetically targeted treatment options for ALS. Mutations in the SOD1 gene are responsible for around 2% of the approximately 168,000 people with ALS worldwide (SOD1-ALS).

About Ionis Pharmaceuticals, Inc.

For more than 30 years, Ionis has been the leader in RNA-targeted therapy, opening new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed drugs and a leading late-stage pipeline highlighted by industry-leading cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision to become a leading, fully integrated biotechnology company.

To learn more about Ionis, visit and follow us on Twitter @ionispharma.

Ionis Forward-Looking Statements

This press release contains forward-looking statements regarding Ionis’ business and the therapeutic and commercial potential of Ionis’ technologies, tofersen and other products in development. Any statement describing Ionis’ objectives, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. These statements are subject to certain risks and uncertainties, including those related to the impact that COVID-19 may have on our business, and including, but not limited to, those related to our commercial products and pharmaceuticals. our pipeline, and in particular those inherent in the process of discovering, developing and commercializing safe and effective drugs for human therapeutic use, and in the effort to build a business around these drugs. Ionis’ forward-looking statements also involve assumptions which, if they never materialize or prove to be incorrect, could cause its results to differ materially from those expressed or implied by such forward-looking statements.

Although Ionis’ forward-looking statements reflect the good faith judgment of its management, such statements are based solely on facts and factors currently known to Ionis. Accordingly, you are cautioned not to rely on these forward-looking statements. These and other risks relating to Ionis’ programs are further described in Ionis’ Annual Report on Form 10-K for the fiscal year ended. December 31, 2021, and the most recent quarterly filing of Form 10-Q, which are filed with the Securities and Exchange Commission. Copies of these and other documents are available from the Company.

In this press release, unless the context otherwise requires, “Ionis”, “Company”, “we”, “us” and “our” refer to Ionis Pharmaceuticals and its subsidiaries.

Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

SOURCEIonis Pharmaceuticals, Inc.


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