Biogen Abandons Ionis Assets in ALS, Angelman Syndrome Post Early Results

Biogen and Ionis Pharmaceuticals announced early results from their Phase I/II ALSpire study on Thursday, revealing that their experimental antisense oligonucleotide BIIB105 did not achieve significant reductions in plasma levels of a neurodegeneration biomarker, nor did it improve clinical outcomes for patients with amyotrophic lateral sclerosis (ALS). Consequently, the companies have decided to halt the development of BIIB105.

The ALSpire study was designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of intrathecal BIIB105 in adult ALS patients through a multiple-ascending-dose trial. This trial included a six-month placebo-controlled phase, followed by a three-year, long-term open-label extension phase.

In the recent announcement, Biogen and Ionis confirmed that BIIB105 did not significantly lower plasma neurofilament light chain (NfL) levels, a biomarker linked to nerve damage and neurodegeneration. Additionally, the investigational drug did not show any meaningful clinical improvements in patient function, respiratory capacity, or muscle strength.

Data from ALSpire’s open-label phase corroborated the initial six-month findings, as BIIB105 continued to show no significant impact on NfL levels or clinical measures. Despite BIIB105’s ability to significantly reduce the ataxin-2 (ATXN2) protein in cerebrospinal fluid, Biogen found this result insufficient. Stephanie Fradette, head of Biogen’s neuromuscular development unit, stated that the latest data “gives us confidence that BIIB105 did not slow the disease process.”

Biogen and Ionis plan to further analyze the ALSpire data to gain a deeper understanding of the disease mechanisms and the effects of BIIB105. The companies intend to present their findings at the European Network to Cure ALS meeting in June 2024.

William Blair analyst Myles Minter described the ALSpire outcome as “obviously disappointing,” although not unexpected. He noted the high risk associated with developing treatments for sporadic ALS, particularly due to the absence of a clear human genetic link for ATXN2. Minter also pointed out that the discontinuation of BIIB105 follows other setbacks in the ALS treatment field, such as the withdrawal of Amylyx’s Relyvrio (sodium phenylbutyrate and taurursodiol) in April 2024.

On the same day, Biogen announced its decision not to exercise its option to license and further develop another Ionis antisense oligonucleotide candidate, BIIB121, intended for the treatment of Angelman syndrome. This decision comes despite positive Phase I/IIa data for BIIB121, also known as ION582, which demonstrated improvements in cognition, communication, and motor function in patients.

Minter suggested that Biogen’s decision to forgo further development of BIIB121 might reflect its strategy to reprioritize early-stage research and development efforts. He noted that the promising results for ION582 make it a “natural fit” for Ionis, given the company’s focus on rare neurological diseases.