First Patient Treated in Phase 2/3 Trial Assessing Higher Dose of Spinraza

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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The first patient has been dosed in the Phase 2/3 DEVOTE trial assessing the safety, tolerability, and efficacy of a higher dose of Spinraza (nusinersen) in patients of all ages with spinal muscular atrophy (SMA), Biogen has announced.

Spinraza, the first disease-modifying treatment approved by the U.S. Food and Drug Administration (FDA) for different forms of SMA, works by increasing production of the survival motor neuron (SMN) protein by the SMN2 “backup” gene (a gene similar to SMN1) that usually remains unaffected in people with SMA.

The medication is given by an injection directly into the spinal canal (intrathecal injection) to overcome its inability to cross the blood-brain barrier — a highly selective, semipermeable membrane that isolates the brain from the rest of the blood circulating in the body.

“As the first treatment for SMA, Spinraza fundamentally shifted the disease course compared to natural history, allowing many individuals to reach milestones that may have been previously unattainable,” Alfred Sandrock Jr., MD, PhD, executive vice president of research and development at Biogen, said in a press release. “With the success we’ve seen to date with the 12 mg dose, we are exploring a higher dose of Spinraza for the potential to deliver even better clinical outcomes,” Sandrock said.

The Phase 2/3 DEVOTE trial (NCT04089566) is enrolling an estimated 125 participants with infantile- or later-onset SMA at approximately 50 clinical sites worldwide.

Besides efficacy, DEVOTE will also evaluate Spinraza’s safety, tolerability, and pharmacokinetics — its absorption, distribution, metabolism, and excretion — in plasma and the cerebrospinal fluid (the liquid surrounding the brain and spinal cord). The medication will be given via intrathecal administration.

The study will be divided into three stages, two of which (A and C) will be open-label, meaning there will be no control group, while the second part (B) will be double-blind and randomized with a control (placebo) group.

In part A, patients with later-onset SMA (most likely SMA type 2 or 3) will receive four 28 mg loading doses of Spinraza, followed by similar maintenance doses four and eight months later.

In part B, patients with infantile-onset (most likely SMA type 1) or later-onset SMA will receive two 50 mg loading doses 14 days apart, followed by a maintenance dose of 28 mg after four and eight months.

During this phase of the trial, there will also be an active control treatment group that will serve as a reference for comparison with the new high dosing regimen. Patients in this control group will receive the current FDA-approved Spinraza treatment regimen, which consists of four loading doses of 12 mg, followed by similar maintenance doses every four months.

In part C, adults who have been treated with the standard regimen of Spinraza for at least one year will receive a single loading dose of 50 mg followed by a maintenance dose of 28 mg four and eight months later. This phase of the study is aimed at evaluating the safety and tolerability of transitioning patients already on Spinraza to higher doses.

Despite the COVID-19 pandemic, as of right now, Biogen anticipates continuing to move forward with current clinical trials testing Spinraza, including DEVOTE.

“The health and safety of our trial participants and their families, as well as the healthcare teams supporting our trials, is our primary concern. We have an important responsibility to patients in our current trials and as of now, all open Spinraza clinical trials are moving forward. We are working with each site, patients and their families to manage the evolving impact of COVID-19 on the scheduling of patient doses,” Biogen said in an emailed statement to SMA News Today.