Biogen presented data from the end of the Phase 3 study on Spinraza™ (CHERISH) at a plenary session of the American Academy of Neurology (AAN) annual meeting in Boston on 24th April 2017. This data demonstrated a highly statistically significant and clinically meaningful improvement in motor function in children with later-onset (most likely to develop Type 2 or Type 3) SMA compared to untreated children. The overall findings continue to support the robust efficacy and favourable safety profile of Spinraza™ across a broad range of individuals with SMA. The Spinraza™ development program represents the largest body of clinical data of its kind in SMA.
“The CHERISH study, conducted in collaboration with Ionis, further demonstrates the meaningful impact SPINRAZA can have in children with later-onset SMA, and reaffirms the benefit of treatment across SMA populations,” said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. “Our clinical development program demonstrates the impact of early treatment, which is confirmed by NURTURE data showing significant motor milestone improvements generally consistent with normal development in presymptomatic infants treated with SPINRAZA.”
CHERISH: Later-onset SMA (Most Likely to Develop Type 2 or Type 3)
CHERISH is a Phase 3, multicentre, randomised, double-blind, sham-procedure controlled study to assess the efficacy and safety of Spinraza™ in children with later-onset SMA. The 15-month study investigated Spinraza™ in 126 non-ambulatory children 2 to 12 years old who experienced symptom onset at greater than 6 months of age.
In the CHERISH end of study analysis, children on Spinraza™ demonstrated a highly statistically significant and clinically meaningful improvement in motor function, as observed by the treatment difference of 4.9 points in the mean change from baseline to Month 15 in the Hammersmith Functional Motor Scale Expanded (HFMSE) score (p=0.0000001). The HFMSE is a validated tool specifically designed to assess motor function in children with SMA. When measuring changes from baseline, children who received Spinraza™ (n=84) achieved a 3.9 point mean improvement at Month 15, while children who were not on treatment (n=42) experienced a mean decline of 1.0 point. Primary endpoint results of the end of study analysis were consistent with results observed at the interim analysis.
Data from the other endpoints analysed, including attainment of new motor milestones and upper limb motor function, were consistently in favour of children who received treatment.
Spinraza™ demonstrated a favourable safety profile. Treatment-emergent adverse events (AEs), severe AEs and serious AEs (SAEs) were reported less frequently in children treated with Spinraza™ than those not on treatment. The majority of the AEs were considered to be either related to SMA disease, common events in the general population, or events related to the lumbar puncture procedure. No children discontinued the study due to AEs.
“In CHERISH, most children with later-onset SMA treated with SPINRAZA saw improvements in motor function and stabilization or slowing of disease progression,” said Dr. Richard Finkel, chief of neurology, Nemours Children’s Hospital, Orlando, Florida. “As a physician who has spent 37 years treating children with SMA, it’s incredibly encouraging to see some patients on SPINRAZA achieve milestones such as crawling and standing with assistance within the clinical trial. These kinds of clinically meaningful improvements are unprecedented and give new hope to individuals with SMA and their families.”
NURTURE: Presymptomatic Infants with SMA
Biogen will also present new interim data from the Phase 2, multicentre, open-label, single-arm NURTURE study evaluating Spinraza™ for the treatment of infants under six weeks old with genetically diagnosed SMA who were presymptomatic at treatment initiation. At the time of the interim analysis, infants (n=20) were enrolled for a median of 317.5 days, and all infants were alive and none required respiratory intervention (chronic non-invasive ventilation, invasive ventilation or tracheostomy). Further, most infants achieved motor milestone and growth parameter gains generally consistent with normal development, such as head control, independent sitting, standing and walking independently, as measured by validated scales.
Three infants experienced AEs considered possibly related to Spinraza™ by the investigator, all of which were resolved. No infants have discontinued or withdrawn from the study due to AEs, and no new safety concerns have been identified.
“The results from NURTURE are significant, as they continue to demonstrate the importance of beginning SPINRAZA treatment as soon as possible after an SMA diagnosis and the major impact that early treatment may have across a broad range of SMA populations,” said Sandrock.
The CHERISH and NURTURE slide presentations will be available concurrently with the AAN sessions on the Investor section of the Biogen company website, www.Biogen.com.
SPINRAZA Program Status
Biogen licensed the global rights to develop, manufacture and commercialize Spinraza™ from Ionis Pharmaceuticals, a leader in antisense therapeutics. Biogen and Ionis conducted an innovative clinical development program that moved Spinraza™ from its first dose in humans in 2011 to its first regulatory approval by the United States Food and Drug Administration (FDA) in 2016.
Spinraza™ was first approved by the FDA on December 23, 2016 within three months of regulatory filing for the treatment of SMA in paediatric and adult patients. In April 2017, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the granting of a marketing authorization for Spinraza™ for the treatment of 5q SMA, following review under an Accelerated Assessment program. A decision from the European Commission (EC) is expected in the next few months. Biogen has also submitted regulatory filings in Japan, Canada, Australia and Switzerland and plans to initiate additional filings in other countries in 2017.