Salanersen for Spinal Muscular Atrophy

(STELLAR-1 Trial)

Overseen By Global Biogen Clinical Trial Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Biogen

Must not be taking: SMA therapies, Myostatin inhibitors

Disqualifiers: SMA symptoms, Areflexia, Hypoxemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 19

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness and safety of salanersen for babies diagnosed with spinal muscular atrophy (SMA) through genetic testing before symptoms appear. Researchers seek to determine if early administration of salanersen can prevent or reduce SMA symptoms by increasing the production of SMN protein, essential for muscle and nerve function. Babies who may qualify for this trial have two or three SMN2 gene copies and no visible signs of SMA. The study involves administering salanersen through injections into the fluid around the brain and spinal cord over several months. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for SMA.

Is there any evidence suggesting that salanersen is likely to be safe for humans?

Research has shown that salanersen is generally safe, as earlier studies have demonstrated. Data from past trials indicated that salanersen was mostly well-tolerated, even at different doses, which is encouraging for its safety in treating spinal muscular atrophy (SMA).

Additionally, a study with children who have SMA and had previously received gene therapy found that salanersen helped slow the loss of nerve cells. While this offers some understanding of its effects, it's important to remember that earlier studies often involve fewer participants. Safety information can change as more people use the treatment.

Overall, previous findings suggest salanersen might be safe, but ongoing studies will provide more complete information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for SMA?

Salanersen is unique because it is administered directly into the spinal fluid via an intrathecal lumbar puncture, which allows for targeted delivery to the central nervous system. This is different from most treatments for Spinal Muscular Atrophy (SMA), like nusinersen, which also uses intrathecal delivery but with a different dosing schedule. Researchers are excited about Salanersen because it potentially offers a more extended dosing interval—approximately 12 months apart—compared to the more frequent dosing schedules of existing therapies. This could mean fewer hospital visits and an improved quality of life for patients.

What evidence suggests that salanersen might be an effective treatment for spinal muscular atrophy?

Research has shown that salanersen helps the SMN2 gene produce more SMN protein, which is essential for the proper functioning of motor neurons and muscles. Early results suggest that salanersen can slow nerve damage in children with spinal muscular atrophy (SMA), potentially leading to fewer or less severe symptoms. In past studies, salanersen was generally well tolerated and showed promise in preventing or reducing the severity of SMA symptoms. Participants in this trial will receive salanersen as part of the study's treatment plan. ^{1 2 3 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for babies diagnosed with SMA who have not shown symptoms yet. They must weigh in the 3rd percentile or higher, be 42 days old or younger at first dose, and have two or three copies of the SMN2 gene. A genetic test confirming SMA and a specific nerve signal strength are also required.

Inclusion Criteria

My weight is in the top 3% for my age according to WHO standards.

Ulnar compound muscle action potential (CMAP) amplitude ≥2 millivolt (mV) at Screening and Day 1 predose

I am 42 days old or younger receiving my first dose of salanersen.

Exclusion Criteria

Areflexia on neurologic examination at biceps, knee, or ankle at Screening or Day 1 Predose

Any reason, anatomical or otherwise (including hematology/coagulation laboratory results), that presents increased risk of complication from the LP procedures or safety assessments

My doctor suspects I have SMA based on my symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment Part 1

Participants receive 2 doses of salanersen, 12 months apart, with up to 11 clinic visits and 3 phone calls

25 months

11 visits (in-person), 3 calls (virtual)

Treatment Part 2

Participants continue to receive salanersen with up to 3 doses, 12 months apart, with up to 7 clinic visits and 12 phone calls

36 months

7 visits (in-person), 12 calls (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Salanersen

Trial Overview The study tests salanersen's effects on preventing or reducing SMA symptoms when given before they appear. Babies will receive intrathecal injections of salanersen over two parts: initially two doses about a year apart, followed by up to three more doses at yearly intervals.

How Is the Trial Designed?

Group I: Salanersen Experimental Treatment 1 Intervention

In Part 1 of the study, participants will receive two doses of salanersen, 80 milligrams (mg) by intrathecal (IT) lumbar puncture (LP), approximately 12 months apart. Participants who complete Part 1 of the study will receive three doses of salanersen, 80 mg by IT LP, approximately 12 months apart, in Part 2 of the study.

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Citations

1. investors.biogen.com investors.biogen.com/news-releases/news-release-details/biogen-advance-investigational-spinal-muscular-atrophy-asset

Biogen to Advance Investigational Spinal Muscular Atrophy ... The cumulative data from the Phase 1 study indicate that salanersen has a generally well tolerated safety profile at both the 40 mg and 80 ...

2. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-biogen-advance-salanersen-sma-registrational

Ionis announces Biogen to advance salanersen into SMA ... Interim Phase 1 data show children with SMA previously treated with gene therapy experienced a substantial slowing of neurodegeneration.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07221669

A Study to Learn About Salanersen's (BIIB115) Effects on ... Salanersen works by helping the SMN2 gene to make more SMN protein. In this study, participants will have either 2 SMN2 copies or 3 SMN2 copies.

4. neurologylive.com neurologylive.com/view/antisense-agent-salanersen-shows-promising-phase-1-data-spinal-muscular-atrophy

Biogen's Salanersen Shows Promising Phase 1 Data in ... New phase 1 data revealed salanersen's promise to slow neurodegeneration in spinal muscular atrophy, potentially paving the way for future phase 3 trials.

5. curesma.org curesma.org/biogen-announces-advancement-of-investigational-sma-drug-salanersen-to-registrational-trials-based-on-positive-phase-1-results/

Biogen Announces Advancement of Investigational ... In pediatric participants previously treated with gene therapy, salanersen demonstrated a substantial slowing of neurodegeneration and ...

6. mytomorrows.com mytomorrows.com/trials/sma-stellar-1/en-us/

STELLAR-1: A clinical study for children with SMA The STELLAR-1 Study is evaluating the effect salanersen has on infants diagnosed with spinal muscular atrophy (SMA) through genetic testing.