Disappointed with Phase I/II results for two Ionis-partnered programs, one for amyotrophic lateral sclerosis and another for Angelman syndrome, Biogen has opted to not proceed with their development.
Biogen and Ionis Pharmaceuticals on Thursday revealed early results from the Phase I/II ALSpire study, demonstrating that their investigational antisense oligonucleotide BIIB105 failed to significantly lower plasma levels of a neurodegeneration biomarker, or improve clinical outcomes, in amyotrophic lateral sclerosis patients.
Given the disappointing outcome, the partners have elected to discontinue the development of BIIB105.
ALSpire was a multiple-ascending-dose trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of intrathecal BIIB105 in adult patients with amyotrophic lateral sclerosis (ALS). The study consisted of a six-month placebo-controlled study, followed by a three-year, long-term, open-label extension phase.
In Thursday’s announcement, Biogen and Ionis revealed that the antisense oligonucleotide was unable to significantly reduce the levels of plasma neurofilament light chain (NfL), a known indicator of nerve damage and neurodegeneration. BIIB105 also showed no meaningful clinical impact on patient function, breathing and strength.
Data from ALSPire’s open-label phase were similar to its initial six-month outcomes, with BIIB105 having no significant impact on NfL or clinical measures.
While BIIB105 did significantly reduce levels of the ataxin-2 (ATXN2) protein in patients’ cerebrospinal fluid, this was not enough for Biogen. Stephanie Fradette, head of the company’s neuromuscular development unit, said in a statement that Thursday’s readout “gives us confidence that BIIB105 did not slow the disease process.”
Biogen and Ionis will continue to evaluate ALSpire’s data to better understand the “underlying disease process and effects of BIIB105.” The companies will present their analysis at the upcoming European Network to Cure ALS meeting in June 2024.
William Blair analyst Myles Minter in an investor note said that the outcome of ALSpire was “obviously disappointing,” though not surprising.
“We have maintained the view that the program was interesting but highly risky given known challenges in developing treatments for sporadic ALS and lack of a clear human genetic link for ATXN2,” Minter wrote, adding that BIIB105’s discontinuation adds to the setbacks in the ALS field, following the withdrawal of Amylyx’s Relyvrio (sodium phenylbutyrate and taurursodiol) in April 2024.
Biogen on Thursday also announced that it would not exercise its option to license and take charge of the development of another Ionis antisense oligonucleotide candidate, dubbed BIIB121, for the treatment of Angelman syndrome.
The announcement comes after Ionis posted positive Phase I/IIa data for BIIB121, also known as ION582, showing that the investigational treatment improved cognition, communication and motor function in patients.
“While it is difficult to speculate the exact rationale for Biogen’s decision, particularly without the full dataset, Biogen has previously emphasized plans to reprioritize its early-stage R&D efforts, so we are not particularly surprised by Thursday’s update,” Minter wrote in the investor note, adding that ION582 is a “natural fit” for Ionis, given the biotech’s “focus on rare neurological diseases.”
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
