information: Presentation of results at a congress
Announcement: presentation of results at the 23rd Annual Congress of the World Muscle Society (WMS)
Company: Biogen (USA - MA)
Product: Spinraza® (nusinersen)
- antisense oligonucleotide. The SMN protein is made by two genes, the SMN1 and SMN2 genes. Most patients with spinal muscular atrophy lack the SMN1 gene but have the SMN2 gene, which mostly produces a ‘short’ SMN protein which cannot work properly on its own. Nusinersen (ISIS-SMNRx ) is designed to alter the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. It is expected to make the SMN2 gene produce adequate levels of the SMN protein of normal length, thereby increasing the survival of motor neurons.
- Spinraza™ was discovered and developed by Ionis and Biogen. Biogen exercised its option to worldwide rights to nusinersen in August 2016. Biogen is responsible for future development, manufacturing, and commercialization of Spinraza™ . Under the terms of the January 2012 agreement, Ionis is responsible for global development and Biogen Idec has the option to license the compound until completion of the first successful Phase 2/3 study or the completion of two Phase 2/3 studies. Both the U.S. and EU have granted nusinersen Orphan Drug status. Additionally, both the U.S. and EU regulatory agencies have granted special status to nusinersen, including Fast Track Designation and Priority Review in the U.S. and Accelerated Assessment in the EU.
- Spinraza® is the first and only approved medicine for the treatment of spinal muscular atrophy (SMA) and is currently approved in the U.S., the European Union, Japan and Brazil, among other countries. Biogen has submitted regulatory filings in additional countries and plans to initiate additional filings in other countries. As of June 30, 2018, more than 5,000 individuals with SMA are being treated with SPINRAZA worldwide, based on patients across the post-marketing setting, Expanded Access Program (EAP) and clinical trial participants.
Disease: spinal muscular atrophy (SMA)
area: Rare diseases - Genetic diseases - Neuromuscular diseases
Country: Australia, Germany, Italy, Qatar, Taïwan, Turkey, USA
- The primary objective of the study is to examine the efficacy of multiple doses of Nusinersen administered intrathecally in preventing or delaying the need for respiratory intervention or death in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (SMA). Secondary objectives of this study are to examine the effects of Nusinersen in infants with genetically diagnosed and presymptomatic SMA. (NCT02386553)
- • On October 6, 2018, Biogen announced new interim results from NURTURE, an ongoing open-label, single-arm efficacy and safety study of Spinraza® (nusinersen) in 25 presymptomatic infants with SMA. The data have been presented at the 23rd Annual Congress of the World Muscle Society (WMS) held in Mendoza, Argentina.
- The interim analysis evaluated survival and respiratory intervention rates in infants (n=25) who were genetically diagnosed with SMA and began treatment in the presymptomatic stage of the disease. As of May 2018 all patients in the study were alive and none required tracheostomy or permanent ventilation. Additionally, 22 of the 25 participants were able to walk either with assistance or independently according to the motor milestone standard of the World Health Organization and all 25 were able to sit without support.
- The motor skills of study participants were also evaluated using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), an assessment which considers 16 different types of movement to create an overall score between zero and 64. The mean CHOP INTEND scores were 62.6 for study participants with three copies of the SMN2 gene and 61.0 for those with two copies of the gene.
- All NURTURE study participants were 14 months or older at the time of the analysis. Participants included infants with two copies of the SMN2 gene (n=15) who are likely to develop a fatal, early-onset form of SMA known as Type 1, and infants with three copies of the SMN2 gene (n=10) who typically develop SMA Type 2 or 3. People living with SMA Types 2 and 3 may never be able to walk or will lose that ability over time. No new safety concerns were identified.
- Additional research presented at WMS compared levels of phosphorylated neurofilament heavy chain (pNF-H) in plasma in more than 300 patients from Spinraza® clinical trials, including those in the NURTURE study, and a control group of people without SMA. The data demonstrated that treatment with Spinraza® is associated with a rapid decline followed by stabilization of pNF-H in plasma at levels close to those of healthy controls. The results are part of Biogen’s ongoing work to identify and validate biomarkers that could provide insight on the disease progression of SMA.
- • On March 12, 2018, Biogen announced new interim Phase 2 results from NURTURE, the ongoing open-label, single-arm study evaluating the efficacy and safety of Spinraza® (nusinersen) among pre-symptomatic infants with spinal muscular atrophy. In NURTURE, all infants treated with SPINRAZA were alive, did not require permanent ventilation and showed improvement in motor function and motor milestone achievements as of July 5, 2017, compared to the disease’s natural history. This study has been presented at the Muscular Dystrophy Association (MDA) Clinical Conference on March 11-14, 2018, in Arlington, Virginia.
- In the NURTURE study, Spinraza® was administered to infants six weeks old or younger (n=25), who were in the pre-symptomatic stage, genetically-diagnosed with SMA and had two or three copies of the SMN2 gene (n=15 for two copies (most likely to develop Type 1 SMA); n=10 for three copies (most likely to develop Type 2 SMA)). At the time of this interim analysis, infants had been followed for up to 25.6 months – well beyond the typical timeframe when most infants with Type 1 SMA would have required permanent ventilation or died. The interim analysis, titled, “Nusinersen in Infants Who Initiate Treatment in a Pre-Symptomatic State of SMA: Interim Efficacy and Safety Results from the Phase 2 NURTURE Study,” showed that all infants were alive and none required tracheostomy or permanent ventilation.
- NURTURE participants also achieved a mean CHOP INTEND score, which measures general motor function among infants with SMA, of 58.4 at last visit (out of a maximum score of 64). Many continue to improve and maintain these scores beyond a point in time at which untreated individuals with Type 1 SMA would experience a significant decline. Overall, the study showed that Spinraza® was well-tolerated and no new safety concerns were identified.