Aiming to Halt Disease Progression at its Root

Biogen is actively conducting a global Phase 3 clinical trial (STELLAR-1, NCT07221669) of its novel drug candidate, Salanersen (BIIB115), to evaluate the safety and efficacy in infants with Spinal Muscular Atrophy (SMA) who are in the pre-symptomatic stage. This represents a paradigm shift from the current treatment approach, which focuses on treating the disease after neurological damage has occurred, and is attracting significant attention from both the academic and industrial communities. The trial targets infants under 6 weeks of age who have been genetically diagnosed, with the goal of preventing lifelong motor impairments through early intervention.

Innovative Mechanism Targeting the SMN2 Gene

Salanersen is an antisense oligonucleotide (ASO) therapeutic administered via intrathecal injection. It binds to SMN2 pre-mRNA to promote the production of SMN protein within nerve cells. While its mechanism is similar to Spinraza (nusinersen), it has undergone modifications to its chemical backbone, resulting in improved drug efficacy and target binding. This is expected to overcome the limitations of the previous 4-month administration schedule, allowing for sufficient therapeutic concentrations to be maintained in the cerebrospinal fluid (CSF) with only annual administration.

Efficacy Demonstrated Through Motor Milestone Achievement

The primary endpoint of the STELLAR-1 Phase 3 trial focuses on whether infants achieve key motor milestones as they grow. Specifically, for infants with two copies of the SMN2 gene, the objective is to assess whether they can sit independently by 12 months of age, and for infants with three copies, whether they can walk independently by 18 months of age. This is a sophisticated design aimed at directly demonstrating that the drug administered into the spinal cord effectively inhibits severe neurological damage in infants and preserves physical function in the long term, going beyond simply increasing protein levels.

Competition Among Three Companies and Strategy to Defend Market Share

The global SMA treatment market is currently dominated by three major players: Spinraza, with annual sales of $1.55 billion; Zolgensma, a gene therapy with annual sales of $1.23 billion; and Evrysdi, an oral therapy with annual sales of approximately $2 billion. Biogen aims to regain market leadership and defend against Spinraza's declining sales by maximizing the convenience of Salanersen, which offers annual administration. The drug has also received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA), reflecting its high commercial potential.

Strategic Partnership with Ionis and Deal Terms

This pipeline represents a key deal in which Biogen paid Ionis Pharmaceuticals an upfront payment of $60 million in January 2022 to acquire exclusive global development and commercialization rights. Biogen will pay Ionis milestone payments based on clinical progress and commercial success, as well as tiered royalties based on global sales. This can be seen as a crucial financial investment for Biogen to strengthen its neurology portfolio and maintain a leading position in the rare disease therapeutics field.