2 Spinraza Trials Now Enrolling, With ASCEND Testing Higher Dose

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by Steve Bryson PhD |

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Spinraza trials now enrolling | SMA News Today | announcement illustration of woman with megaphone

Children, teenagers, and adults with later-onset spinal muscular atrophy (SMA), previously treated with Evrysdi (risdiplam), can now enroll in a new Phase 3b clinical trial to determine the efficacy of a higher dose of Spinraza (nusinersen).

Biogen, the company that markets Spinraza, announced the enrollment of the open-label trial, dubbed ASCEND (NCT05067790), on a Cure SMA webinar, and provided an update on the progress of other Spinraza clinical trials for the patient community.

The Phase 3b trial is set to run for roughly 2.5 years and expects to enroll up to 135 patients at 40 sites worldwide. Participants must be between ages 5 to 39, and unable to walk.

Enrollment is currently open at four of the 12 planned U.S. sites — in Arkansas, Georgia, North Carolina, and Virginia. For further information on locations and contacts, click here.

Eligible participants must have been treated with Evrysdi at its approved 5 mg dose and weigh more than 20 kg (about 44 lbs). Also required is a pre-specified range of arm movement, as assessed by the Revised Upper Limb Module (RULM) test, a measure of upper limb motor function. Patients may or may not have received Spinraza before Evrysdi.

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During the trial, participants will receive two 50 mg loading doses of Spinraza, delivered two weeks apart by intrathecal (spinal canal) injection. This will be followed by a maintenance dose of 28 mg, which is higher than the approved maintenance dose of 12 mg, every four months.

Improvements in upper limb function, as assessed by RULM, is the trial’s main goal. Alongside safety, additional outcomes include Spinraza’s impact on motor function, using the Hammersmith Functional Motor Scale Expanded (HFMSE), as well as caregiver burden.

Evrysdi, marketed by Roche and Genentech, is approved up to 5 mg for SMA patients ages 2 months and older, and the flavored liquid is given daily at home by mouth or feeding tube. For those under 20 kg, dosing is weight-based.

A small molecule, Evrysdi is designed to increase the levels of SMN protein, which are abnormally low in SMA patients. SMN plays an essential role in the health of motor neurons, the specialized nerve cells that control voluntary body movements. Spinraza also enhances SMN production but is an antisense oligonucleotide-based therapy.

In another Biogen announcement, enrollment in the open-label RESPOND trial (NCT04488133) has now reached 28% of its expected 60 participants. The Phase 4 study is testing the efficacy of Spinraza in SMA infants and children between 3 months and 3 years of age, who responded poorly to the gene therapy Zolgensma.

Of note, a Phase 4 trial is launched after a medicine has been approved, typically to monitor its performance in a real-life setting or, as in the RESPOND trial, address the needs of patients who previously failed to respond to other treatments.

Enrollment is ongoing at 11 sites in the U.S., two sites each in Spain and Italy, and one in Israel. More information on contacts and locations can be found here.

Eligible patients for RESPOND must have received the single Zolgensma dose at least three months prior to Spinraza, which will be given in four 12 mg loading doses, followed by 12 mg maintenance doses every four months for almost two years.

Among the 60 planned participants, the trial aims to enroll about 40 infants up to 9 months of age who received Zolgensma at 6 months or younger. This group is meant the examine Spinraza’s benefits among younger patients with a shorter mean interval between the two treatments. The remaining participants, approximately 20 in total, will be children up to age 3.

RESPOND’s primary outcome is improvements in certain developmental milestones, such as sitting, crawling, head control, standing, and walking — as measured by the Hammersmith Infant Neurological Examination Section 2 motor milestone score.

Lastly, Biogen reported the first participants who joined the open-label extension trial SHINE (NCT02594124), which started in 2015, will complete the study this year. The five-year SHINE study is the largest long-term extension trial of Spinraza, including nearly 300 patients across 14 countries who previously participated in various primary clinical trials. Information from SHINE has been reported in more than 20 medical journal presentations.

SHINE’s interim findings, which reported up to 6.5 years of Spinraza treatment for some patients, showed sustained benefits — from improvement in motor skills to disease stabilization — in a wide range of SMA patients who now are toddlers and young adults.