Rare Daily Staff

Biogen reported new research supporting the continued development of an experimental higher dose of Spinraza and additional data reinforcing the strength of Spinraza’s clinical profile in improving the lives of individuals with spinal muscular atrophy over the long term.

These data are being presented at the virtual Cure SMA Research & Clinical Care Meeting taking place June 9-11, 2021.

“The data we are presenting at Cure SMA 2021 demonstrate the long-term benefits with Spinraza as individuals age. Additionally, a new analysis provides further support for the potential for a higher dose of Spinraza to offer even greater improvements in motor function for SMA patients,” said Alfred Sandrock, head of research and development at Biogen.

SMA is a rare, genetic, neuromuscular disease characterized by a loss of motor neurons in the spinal cord and lower brain stem, resulting in progressive muscle atrophy and weakness. SMA is caused by a deficiency in the production of survival motor neuron (SMN) protein due to a damaged or missing SMN1 gene, with a spectrum of disease severity. Some individuals with SMA may never sit; some sit but never walk; and some walk but may lose that ability over time. In the absence of treatment, children with the most severe form of SMA would not be expected to reach their second birthday. SMA impacts approximately one in 11,000 live births in the United States and is a leading cause of genetic death among infants.

Spinraza is approved to treat infants, children and adults with SMA and is available in more than 50 countries. It is an antisense oligonucleotide that targets the root cause of SMA by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body. It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts.

An analysis of data from the phase 2 CS3A and phase 3 ENDEAR studies in children with infantile-onset SMA used pharmacokinetic (PK)/pharmacodynamic (PD) modelling to predict the potential efficacy of an experimental higher dose regimen of Spinraza, which suggests that a higher dose may lead to a clinically meaningful increase in the CHOP INTEND (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders) score beyond that already observed with the 12 mg approved dose. These findings further reinforce the scientific rationale for the evaluation of a higher dose of Spinraza in the ongoing DEVOTE study, an ongoing trial evaluating the safety, tolerability, and potential for even greater efficacy of a higher dose administration that the currently approved dose. It is a three-part study that includes an open-label safety evaluation cohort (Part A), a pivotal, double-blind, randomized, active-controlled treatment cohort (Part B), and an open-label cohort of patients transitioning from the approved 12 mg dosing regimen of SPINRAZA to the higher dose regimen (Part C).

Safety data from Part A (n=6; 28 mg) support continued development of a higher dose of Spinraza and an updated analysis presented at the meeting includes data collected up to 10 months. Enrollment in the pivotal Part B of DEVOTE is ongoing and will evaluate a higher-dose regimen (two loading doses of 50 mg 14 days apart followed by 28 mg maintenance doses every four months) compared to the currently approved dosing regimen for Spinraza.

An analysis of data from the NURTURE study (n=25) shows 92 percent of patients who initiated SPINRAZA treatment as pre-symptomatic infants maintained the ability to swallow after a median of 3.8 years. This is in contrast with the natural history of SMA where impaired swallowing is expected for people with 2 or 3 SMN2 copies and can lead to an increased risk of aspiration pneumonia, choking and failure to thrive. In this analysis, NURTURE study participants were consistently rated by their caregiver as, on average, never to rarely experienced difficulty for the majority of measures related to general feeding, drinking liquids and eating solid foods. Additionally, all participants with 3 SMN2 copies and 73 percent (11 of 15) of participants with 2 SMN2 copies were reported by their caregiver as being fed exclusively by mouth.

In addition, post-hoc data from the open-label CS2-CS12 and SHINE extension studies indicate children and teens with later-onset SMA (n=14) showed improvement in walking distance over five years of SPINRAZA treatment and stabilization in fatigue.

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