Biogen Inc. announced plans to initiate a global Phase 3b clinical study, ASCEND. The ASCEND study is designed to evaluate the clinical outcomes and assess the safety of a higher dose of nusinersen in children, teens and adults with later-onset spinal muscular atrophy (SMA) following treatment with Evrysdi® (risdiplam). People with SMA do not produce enough survival motor neuron (SMN) protein, which is critical for the ongoing maintenance of motor neurons that support sitting, standing and movement. Over time, people with SMA may lose their ability to perform everyday activities, including brushing their teeth, turning on a light switch or drinking from a cup. The goal of treatment in SMA is to sufficiently protect motor neurons and help preserve function. Available data suggest that exposure to Evrysdi diminishes with increased age and weight, with an approximately 40% reduction in drug concentration in adults compared to infants. Evrysdi’s dosing is capped at 5 milligrams (mg) once patients reach 20 kilograms (kg).8 At the approved 12-mg dose, motor neuron exposure to nusinersen remains similar as patients age and grow. Further, nusinersen has demonstrated proven, sustained efficacy and a well-characterized safety profile, with long-term data in patients treated for more than 7 years across ages and SMA types. Taken together, these data support further exploration of whether a higher dose can deliver even greater efficacy to patients. The ASCEND study will assess if nusinersen at a higher dose may address outstanding clinical needs among later-onset SMA patients treated with Evrysdi who want to make a change in their treatment regimen. The same investigational higher dose of nusinersen is also being evaluated in the ongoing DEVOTE study. The ASCEND protocol has been submitted to the U.S. Food and Drug Administration and is planned to be an approximately 2.5-year study projected to enroll up to 135 later-onset, non-ambulatory individuals with SMA (aged 5 to 39). All participants must have been previously treated with Evrysdi at the maximum recommended dose of 5 mg and be willing and able to change their treatment regimen to a higher dose of nusinersen. Participants must also fall within a particular Revised Upper Limb Module (RULM) measurement range to enter the study. Individuals enrolled in ASCEND will receive two loading doses of nusinersen 50 mg two weeks apart, followed by a maintenance dose of 28 mg every four months during the study period. Efficacy is planned to be assessed by RULM. Additional clinical outcomes include safety, Hammersmith Functional Motor Scale Expanded (HFMSE) and caregiver burden. The study will also evaluate upper limb fine motor function in participants aged 13 and older using the mobile application Konectom™, and neurofilament levels as a marker of biological disease activity, both exploratory endpoints. The study aims to include children, teens and adults naïve to treatment with nusinersen, as well as adults who were previously treated with nusinersen prior to Evrysdi. The company aims for the first eligible patients to be enrolled in 2021.