Biogen plans to initiate a Phase IV study evaluating Spinraza in patients with spinal muscular atrophy and treated with Zolgensma.

Biogen Inc. announced it plans to initiate a global Phase IV clinical study, RESPOND, to examine the clinical benefit and assess the safety of Spinraza (nusinersen) in infants and children with spinal muscular atrophy (SMA) who still have unmet clinical needs following treatment with gene therapy Zolgensma (onasemnogene abeparvovec)

“As clinicians, we continue to pursue improved outcomes for infants and children with SMA, and the need for additional benefit in some patients treated with gene therapy has been observed. There is compelling clinical rationale for the potential for additional efficacy with Spinraza in these patients,” said Crystal Proud, M.D., Pediatric Neuromuscular Neurologist, Children’s Hospital of The King’s Daughters, Virginia and a member of the RESPOND study steering committee. “We expect that the RESPOND study will generate valuable data to help inform future treatment decisions for our youngest SMA patients.”

People with SMA do not produce enough survival motor neuron (SMN) protein, which is critical for the maintenance of motor neurons that support sitting, walking and basic functions of life, including breathing and swallowing. The RESPOND study will seek to understand if the proven efficacy of Spinraza and its continuous production of SMN protein may also benefit patients previously treated with gene therapy.

“Available data now show that some patients in the long-term study of Zolgensma have moved on to treatment with Spinraza. We believe that, for certain patients, motor neurons may be insufficiently treated by this gene therapy, and we plan to initiate this study to understand the extent to which Spinraza may potentially improve outcomes,” said Maha Radhakrishnan, M.D., Chief Medical Officer at Biogen. “The impact of Spinraza since its launch has been unprecedented compared to the natural history of the disease, with 100 percent of pre-symptomatic infants in the NURTURE study alive after nearly five years of treatment. More than 10,000 SMA patients have now been treated globally.”

In the long-term study of Zolgensma, it has been reported that, to date, 4 out of 10 patients have been subsequently treated with Spinraza. Based on the planned study design, RESPOND will be a two-year, open-label study to evaluate the efficacy and safety of Spinraza in SMA patients previously treated with Zolgensma to further inform treatment decisions. Efficacy will be assessed by change from baseline on motor function measures, additional clinical outcomes (e.g., swallowing) and caregiver burden. Neurofilament levels, an exploratory endpoint, will also be evaluated as a marker of biological disease activity. The primary study group aims to include 40 infants aged 9 months or younger (at the time of first Spinraza dose) who have 2 copies of SMN2 (likely to develop SMA Type 1) and received Zolgensma at 6 months old or younger. A second study group will include 20 children and will generate data in patients with a broader age range (up to 3 years old at the time of first Spinraza dose).

After a screening period, participants will receive the approved 12 mg dose of Spinraza, which is four loading doses followed by maintenance doses every four months, over the two-year study period.

The company plans to submit the study protocol to the regulatory authorities in the coming months and aims for the first eligible patients to be enrolled in the RESPOND study in Q1 2021. The study is projected to enroll 60 children up to 3 years old who are determined by the investigator to have the potential for additional clinical improvement after receiving Zolgensma. Physicians will evaluate children for participation using criteria that may include one or more of the following: suboptimal motor function (e.g., a score lower than 50 on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]); the need for respiratory support; abnormal swallowing or feeding ability; or other factors deemed relevant by the investigator.