First Patient Treated in Study of Biogen’s Rare Disease Drug

Biogen recently announced that the first patient has been treated in the global clinical study of its rare disease drug, Spinraza (nusinersen), in infants who did not respond to its gene therapy, Zolgensma (onasemnogene abeparvovec). 

The two-year, open-label REPSPOND study will be conducted at 20 sites worldwide and enroll nearly 60 children up to three years of age with spinal muscular atrophy (SMA) who have the potential for additional clinical improvement after receiving Zolgensma. 

The primary study group will include 40 infants aged nine months or younger who have two copies of SMN2 and received Zolgensma at six months old or younger. The second study group will include 20 children up to three years of age at the time of first Spinraza dose.

Participants will receive four 12 milligram doses of Spinraza, followed by maintenance doses every four months, Biogen explained. This will take place over the two-year study period.

The primary endpoint of the study is the total score on Hammersmith Infant Neurological Examination, which consists of 34 items assessing tone, motor patterns, observation of spontaneous movements, reflexes, visual and auditory attention, and behavior.

Secondary endpoints include safety, change from baseline on motor function measures, caregiver burden, and other clinical outcomes such as swallowing,. The outcomes of the study will help researchers to further optimize treatment decisions. 

“SMA treatments have changed what is possible for children born with the disease but they have also raised new questions,” Nicole Gusset, MD, president of SMA Europe and mother of a child with SMA, said in the announcement. “We appreciate that the RESPOND study will collect data to help provide answers so individuals living with SMA can make informed treatment decisions.”

Children living with SMA do not produce enough survival motor neuron (SMN) proteins, which are vital for the maintenance of motor neurons that support sitting, walking, and basic functions of life, a Biogen spokesperson explained. 

In December 2016, Spinraza was the first drug approved to treat children and adults with SMA. In an FDA-sponsored interim analysis of 82 patients at the time, 40 percent of patients treated with Spinraza achieved improvement in motor milestones as defined in the study, while none of the control patients did.

“In clinical practice, there is a sense of urgency to address motor neuron loss in SMA from the earliest sign or even prior to symptoms, to prevent additional disease progression,” Julie Parsons, MD,  a professor of clinical pediatrics and neurology and the Haberfield family endowed chair in pediatric neuromuscular disorders at Children’s Hospital Colorado and the University of Colorado School of Medicine, said in the Biogen announcement. 

“In some patients treated with gene therapy, we have recognized that further motor neuron protection may be needed. Our hope is that results from RESPOND will demonstrate if SPINRAZA can optimize treatment for some of our youngest patients,” continued Parsons who is also the primary investigator of the RESPOND study. 

At the beginning of August, FDA approved Roche’s Evrysdi (risdiplam) for the treatment of patients two months of age or older with SMA.

Evrysdi is the second drug approved to treat SMA, but the first oral drug approved to help patients with the hereditary condition that causes weakness and muscle wasting

FDA approved the drug based on two clinical trials. In the first trial, after 12 months of treatment, 41 percent of patients were able to sit independently for more than five seconds. After 23 or more months of treatment, 81 percent of patients were alive without permanent ventilation.

In the second study, patients showed an average increase of 1.36  in their score at one-year, compared to a 0.19 decrease in patients on the placebo.