Biogen announces first patient treated in RESPOND phase IV study evaluating Spinraza in patients treated with Zolgensma for spinal muscular atrophy.

Biogen Inc. has announced that the first patient has been treated in the global clinical study, RESPOND. The Phase IV study will 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). RESPOND will be conducted at approximately 20 sites worldwide and aims to enroll up to 60 children with SMA. “SMA treatments have changed what is possible for children born with the disease but they have also raised new questions,” said Dr. Nicole Gusset, President of SMA Europe and mother of a child with SMA. “We appreciate that the RESPOND study will collect data to help provide answers so individuals living with SMA can make informed treatment decisions.” Children 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 like breathing and swallowing. The RESPOND study will seek to understand if the proven efficacy of Spinraza and its mechanism of action, which leads to continuous production of SMN protein, may also benefit patients who have been insufficiently treated with gene therapy. RESPOND is a two-year, open-label study to evaluate the efficacy and safety of Spinraza in SMA patients previously treated with Zolgensma to further optimize treatment decisions. The primary endpoint is the total score on the Hammersmith Infant Neurological Examination Section 2. Secondary endpoints include safety, change from baseline on additional motor function measures, other 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 study will 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. It has been reported that, to date, 40 percent of children in the long-term study of Zolgensma have been subsequently treated with Spinraza. Physicians will use 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. The primary study group will 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 within 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: four loading doses, followed by maintenance doses every four months, over the two-year study period. See the study at (NCT04488133).