Thursday, Ionis Pharmaceuticals Inc (NASDAQ:IONS) and Biogen Inc (NASDAQ:BIIB) decided to terminate the development of BIIB105 (ION541), an investigational antisense oligonucleotide (ASO) for amyotrophic lateral sclerosis (ALS) based on topline results from the Phase 1/2 ALSpire study.
BIIB105 was designed to reduce the expression of ataxin-2 (ATXN2) protein and demonstrated statistically significant cerebrospinal fluid (CSF) ATXN2 protein reductions in the study.
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However, over the 6-month placebo-controlled period, treatment with BIIB105 did not result in a reduction in levels of plasma neurofilament light chain (NfL), a marker of neurodegeneration and neuronal damage.
Additionally, BIIB105 did not demonstrate an impact on clinical outcome measures of function, breathing and strength.
"While BIIB105 lowered ATXN2 protein, it did not reduce neurofilament, which gives us confidence that BIIB105 did not slow the disease process," said Stephanie Fradette, Head of the Neuromuscular Development Unit at Biogen.
Longer-term biomarker and efficacy data from the open-label extension were similar to those seen during the 6-month placebo-controlled treatment period, with sustained reductions in ATXN2 but no impact on NfL or clinical outcome measures over 40+ weeks of follow-up.
No evidence of benefit was observed in any subgroup evaluated, including those participants with a Poly-CAG expansion in the ATXN2 gene.
Data analysis from the study is ongoing. The companies will present the BIIB105 Phase 1/2 data at the upcoming European Network to Cure ALS meeting in June.
Concurrently, Ionis Pharmaceuticals reported topline data from the HALOS Phase 1/2a open-label study of ION582 in Angelman syndrome.
ION582 was safe and well tolerated in the study.
ION582 demonstrated consistent improvements across multiple functional domains in Angelman syndrome patients, with improvements observed in key areas of functioning, including cognition, communication, and motor function.
Ionis also announced that it will independently advance ION582 as Biogen has elected not to exercise its option to license ION582.
Ionis plans to review the ION582 Phase 1/2a results with regulatory authorities to align on the design of the pivotal program.
Price Action: IONS shares are down 5.19% at $37.17, and BIIB shares are down 2.12% at $230.33 at last check Thursday.
Illustration of Phrama lab worker created with MidJourney