Biogen is committed to improving health outcomes for people impacted by spinal muscular atrophy (SMA) and generating data to assess if there are treatment pathways to address potential unmet needs. Today, we are excited to announce our intent to initiate a new global SMA clinical trial called ASCEND to understand whether an investigational higher dose of nusinersen* may address unmet medical needs in individuals with SMA following treatment with Evrysdi® (risdiplam).
The ASCEND trial is planned to be an approximately 2.5-year study projected to enroll up to 135 later-onset, non-ambulatory individuals with SMA (aged 5 to 39). The study’s design was informed in part by review of available data of drug exposure of risdiplam by patient weight and age in clinical trials.1,2 The ASCEND study seeks to understand if an investigational higher dose of nusinersen may address unmet medical needs among later-onset SMA patients previously treated with risdiplam. The trial will add to the growing body of evidence informing on the use of the antisense oligonucleotide, nusinersen, as a treatment for pediatric and adult patients with SMA.
When the ASCEND study gets underway, Biogen will have eight active global clinical trials in SMA. Three of these trials – DEVOTE, RESPOND and ASCEND – have been initiated in the past 18 months. These trials are generating crucial data that, together with previous clinical trial results and real-world evidence, will inform the future of SMA treatment. These ongoing efforts, along with others, demonstrate Biogen’s continued commitment to improve the lives of those impacted by SMA.
We wish to acknowledge the hundreds of people who have participated in these important research efforts. The commitment of trial participants and global collaboration of investigators have led to important advancements in knowledge about clinical outcomes for the SMA community, including presentations earlier this year at the annual meetings of the Muscular Dystrophy Association (MDA) and Cure SMA, among others.
For more information about participating in clinical trials, speak with your doctor. For more information about clinical trials sponsored by Biogen, contact [email protected] Please continue reading for Important Safety Information and see accompanying Prescribing Information for SPINRAZA® (nusinersen).
The Biogen Team
*Nusinersen is currently commercialized under the brand name SPINRAZA®, and the U.S. FDA-approved dose is 12 mg.
About the ASCEND Trial
- ASCEND is planned to be an approximately 2.5-year study that includes up to 105 adult, teens, and children naïve to treatment with nusinersen, as well as up to 30 adults who were previously treated with nusinersen prior to risdiplam.
- All participants must have been previously treated with risdiplam at the maximum recommended dose of 5 mg and be willing and able to stop risdiplam treatment to receive the experimental higher dose of nusinersen. Participants must also fall within a particular Revised Upper Limb Module (RULM) measurement range to enter the study.
- Individuals enrolled in ASCEND will receive two loading doses of nusinersen 50 mg approximately two weeks apart, followed by a maintenance dose of 28 mg approximately every four months over the study period.
- Efficacy is planned to be assessed by RULM. Additional clinical outcomes include safety, Hammersmith Functional Motor Scale-Expanded (HFMSE) and caregiver burden. The study will also evaluate upper limb fine motor function in participants aged 13 and older using the mobile application Konectom™, and neurofilament levels as a marker of biological disease activity, both exploratory endpoints.
Questions & Answers
Why aren’t you studying the two treatments being taken at the same time?
Due to the heterogeneity of SMA and complexity of clinical endpoints, a combination arm to the study would increase the number of patients required and lengthen the timeline for the study. Additionally, if both products were used simultaneously, it would be difficult to accurately ascertain which therapy is having an effect in any one patient.
Patients who would like to participate in the study must meet the enrollment criteria. All participants must have been previously treated with risdiplam at the maximum recommended dose of 5 mg and be willing and able to change their treatment regimen to a higher dose of nusinersen and meet additional criteria to be eligible. A complete list of enrollment criteria will be posted on clinicaltrials.gov. Individuals with SMA should discuss treatment decisions with their healthcare providers.
Why aren’t you studying whether there is an impact on health outcomes switching from Evrysdi to the U.S. Food and Drug Administration approved dose (12 mg) of SPINRAZA?
Participants in DEVOTE receive nusinersen, either at the approved 12-mg dose or at the experimental higher dose, whereas all participants in ASCEND will receive the experimental higher dose only. There is no placebo arm in either ASCEND or DEVOTE. However, DEVOTE study participants must be treatment naïve, or previously treated with the approved dose of nusinersen (Part C), and meet additional enrollment criteria. Understanding changes in clinical outcomes as people switch from one treatment other than nusinersen to the other is not possible with the DEVOTE study. The ASCEND study will include participants previously treated with risdiplam and therefore generate data regarding the use of higher-dose nusinersen in this population.
Where will you be recruiting patients for this study?
Plans for the ASCEND study are still being finalized. Enrollment is anticipated to begin before the end of 2021. For more information about clinical trials talk to your doctor.
SPINRAZA® (nusinersen) is a prescription medicine used to treat spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Increased risk of bleeding complications has been observed after administration of similar medicines.
Your healthcare provider should perform blood tests before you start treatment with SPINRAZA and before each dose to monitor for signs of these risks. Seek medical attention if unexpected bleeding occurs.
Increased risk of kidney damage, including potentially fatal acute inflammation of the kidney, has been observed after administration of similar medicines. Your healthcare provider should perform urine testing before you start treatment with SPINRAZA and before each dose to monitor for signs of this risk.
The most common side effects of SPINRAZA include lower respiratory infection, fever, constipation, headache, vomiting, back pain, and post-lumbar puncture syndrome.
These are not all of the possible side effects of SPINRAZA. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Before taking SPINRAZA, tell your healthcare provider if you are pregnant or plan to become pregnant.
Click here to access full Prescribing Information.
This information is not intended to replace discussions with your healthcare provider.
- Evrysdi US FDA SBA documents. Clinical Pharmacology Review(s): Page 41, table 18. The approximately 40% reduction is the percentage difference between risdiplam observed exposures in the youngest infants and adults. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000TOC.cfm. Accessed: July 2021.
- European Medicines Agency: EMA/216061/2021 – Evrysdi EPAR. Page 71, figure 13. The approximately 40% reduction is the percentage difference between risdiplam observed exposures in the youngest infants and adults. Available at: https://www.ema.europa.eu/en/documents/assessment-report/evrysdi-epar-public-assessment-report_en.pdf. Accessed July 2021.
- Based on commercial patients, early access patients, and clinical trial participants through July 2021.