Biogen to launch study of higher Spinraza dose in patients with later onset SMA

Biogen announced it intends to initiate a global phase 3b study to investigate clinical outcomes and safety of a higher dose of Spinraza in patients with later onset spinal muscular atrophy previously treated with Evrysdi.

“We believe that lower drug exposure may be contributing to less-than-optimal treatment outcomes for some patients treated with Evrysdi [risdiplam, Roche],” Maha Radhakrishnan, MD, chief medical officer at Biogen, said in a press release. “The ASCEND study seeks to understand if [Spinraza (nusinersen, Biogen)] may address that unmet medical need and will help inform the future of [spinal muscular atrophy (SMA)] treatment, with the hope of improving patients’ outcomes for the long term.”

Data from prior studies suggested risdiplam exposure decreases as age and weight increase, with adults exhibiting an approximate 40% reduction in drug concentration compared with infants. Upon a patient reaching 20 kg, risdiplam’s dosing is capped at 5 mg.

Motor neuron exposure to nusinersen at the approved dose of 12 mg appeared similar as patients age and grow. Moreover, nusinersen showed proven, sustained efficacy and a well-characterized safety profile, according to the release. Long-term data among patients treated for more than 7 years across ages and types of SMA supported these findings.

In the ASCEND study, researchers will seek to determine whether a higher dose of nusinersen can tackle lingering clinical needs among patients with later onset SMA treated with risdiplan who want to alter their treatment regimen. Researchers in the ongoing DEVOTE study are examining the same investigational higher dose of nusinersen.

The FDA will review the protocol for ASCEND, which is intended to last about 2.5 years and is projected to enroll up to 135 individuals who are nonambulatory, have later onset SMA and are aged 5 to 39 years. Participants must have previously received risdiplam at the maximum 5 mg dose and be willing to alter their treatment regimen to a higher nusinersen dose. They must also fall within a particular Revised Upper Limb Module measurement range to be enrolled, with Biogen aiming to begin enrollment this year.

“There have been significant advances in SMA treatment; however, there is still no cure, and unmet medical needs remain,” Tim Hagenacker, MD, head of the neuromuscular diseases unit at Essen University in Germany and a member of the ASCEND study steering committee, said in the release. “As part of my clinical practice, we’ve observed an opportunity to potentially further improve patient outcomes. With a higher dose of nusinersen, we are positioned to explore what may be possible.”