Taldefgrobep Alfa for Spinal Muscular Atrophy

(RESILIENT Trial)

Not currently recruiting at 73 trial locations

Overseen By

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Biohaven Pharmaceuticals, Inc.

Must be taking: Nusinersen, Risdiplam, Onasemnogene

Must not be taking: Anti-myostatin therapies

Disqualifiers: Respiratory insufficiency, Spinal fusion, others

Stay on Your Current Meds You can continue your current medications while participating

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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether taldefgrobep alfa, an experimental treatment, can safely and effectively complement existing treatments for people with Spinal Muscular Atrophy (SMA) who are already using therapies like nusinersen or risdiplam. The researchers aim to determine if combining taldefgrobep alfa with current therapies can improve outcomes for those with SMA, a genetic disorder affecting muscle strength. Participants will receive either taldefgrobep alfa or a placebo to compare results. Individuals with SMA who are stable on certain treatments and have not used anti-myostatin therapies before may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for SMA.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial requires that you continue your existing treatment with nusinersen, risdiplam, or have a history of onasemnogene abeparvovec.

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

Research has shown that taldefgrobep alfa has been tested in people with spinal muscular atrophy (SMA) and has produced promising results. Previous studies have provided strong safety data, indicating that participants generally tolerate the treatment well. Although some unwanted effects have been reported, they are usually mild and manageable. Trials also suggest that taldefgrobep alfa can enhance movement abilities, a key benefit for those with SMA. Overall, clinical research has demonstrated a positive safety profile for the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for spinal muscular atrophy?

Taldefgrobep Alfa is unique because it targets the myostatin pathway, which plays a role in regulating muscle growth. Unlike traditional treatments for spinal muscular atrophy (SMA) that focus on increasing SMN protein levels, Taldefgrobep Alfa works by potentially promoting muscle growth and strength. This novel approach offers a different angle in treating SMA, sparking excitement among researchers as it could complement existing therapies and provide a new avenue for improving patient outcomes.

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

Research shows that taldefgrobep alfa, which participants in this trial may receive, may help treat spinal muscular atrophy (SMA). In earlier studies, patients experienced significant improvements in their ability to move and control their muscles. Taldefgrobep alfa blocks a protein called myostatin, which usually limits muscle growth. By blocking this protein, the treatment aims to make muscles bigger and stronger. Patients have tolerated it well, experiencing no serious side effects. These findings suggest that taldefgrobep alfa could help improve muscle function for people with SMA. ^{1 2 6 7 8}

Who Is on the Research Team?

Lindsey Lair, MD

Principal Investigator

Biohaven Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for people with Spinal Muscular Atrophy who are already on a stable dose of specific SMA treatments like nusinersen or risdiplam, or have had gene therapy. Participants must weigh at least 15kg and can be ambulant or non-ambulant. Those needing daytime ventilation, recent spinal fusion patients, and those with certain implants or previous anti-myostatin therapies cannot join.

Inclusion Criteria

I can walk with or without assistance.

I have been genetically diagnosed with Spinal Muscular Atrophy.

I am currently on a stable dose of SMA treatment and plan to stay on it.

Exclusion Criteria

I need a ventilator to breathe during the day.

I weigh at least 15kg.

I had spinal fusion surgery less than 6 months ago, but adjustments to MAGEC rods are okay.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive weight-based 35 mg/50 mg weekly subcutaneous injection of taldefgrobep alfa or placebo for 48 weeks

48 weeks

Open-label Extension

Participants receive weight-based 35 mg/50 mg weekly subcutaneous injection of taldefgrobep alfa for 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Taldefgrobep Alfa

Trial Overview The study tests taldefgrobep alfa's effectiveness and safety as an additional treatment for Spinal Muscular Atrophy alongside existing medications compared to a placebo. It aims to see if adding taldefgrobep alfa improves patient outcomes.

How Is the Trial Designed?

Group I: taldefgrobep alfa Experimental Treatment 1 Intervention

taldefgrobep alfa - Double-blind (DB) Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week DB phase. taldefgrobep alfa/taldefgrobep alfa - Extension Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week Open label Extension (OLE) phase.

Group II: Placebo Placebo Group 2 Interventions

Placebo - Double-blind (DB) Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week DB phase. Placebo/taldefgrobep alfa - Extension Phase: Participants who receive placebo during DB phase, receive weight based 35 mg/50 mg weekly subcutaneous taldefgrobep alfa injection for 48-week OLE phase.

Who Is Running the Clinical Trial?

Biohaven Pharmaceuticals, Inc.

Lead Sponsor

Trials

49

Recruited

30,100+

Published Research Related to This Trial

In a study of 21 infants with spinal muscular atrophy (SMA) treated with onasemnogene abeparvovec, 76% achieved at least one World Health Organization motor milestone, indicating significant efficacy in improving motor function.

All children experienced transient side effects, with vomiting being universal and moderate to severe transaminitis occurring more frequently in infants weighing 8 kg or more, highlighting the importance of monitoring and individualized management for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy. D'Silva, AM., Holland, S., Kariyawasam, D., et al.[2022]

In a phase 3 trial involving 22 infants with spinal muscular atrophy type 1, 59% achieved independent sitting for 30 seconds or longer by 18 months, compared to 0% in an untreated cohort, demonstrating significant efficacy of the gene therapy onasemnogene abeparvovec.

91% of treated patients survived without the need for permanent ventilation by 14 months, highlighting the therapy's potential to improve survival outcomes compared to only 26% in the untreated group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Day, JW., Finkel, RS., Chiriboga, CA., et al.[2021]

Citations

1. ir.biohaven.com ir.biohaven.com/news-releases/news-release-details/biohaven-provides-update-taldefgrobep-alfa-development-program

Biohaven Provides Update on Taldefgrobep Alfa ... In the RESILIENT SMA study, taldefgrobep alpha showed clinically meaningful improvements in motor function at all timepoints on the Motor Function Measurement- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05337553

NCT05337553 | A Study to Evaluate the Efficacy and ... Blocking myostatin activity has been shown to increase muscle size and function. Taldefgrobep alfa directly blocks myostatin activity and was well tolerated in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11477173/

Taldefgrobep Alfa and the Phase 3 RESILIENT Trial in Spinal ... Diminished SMN protein levels lead to motor neuron loss, causing muscle atrophy and weakness that impairs daily functioning and reduces quality ...

4. prnewswire.com prnewswire.com/news-releases/biohaven-provides-update-on-taldefgrobep-alfa-development-program-for-spinal-muscular-atrophy-and-obesity-302314979.html

Biohaven Provides Update on Taldefgrobep Alfa ... In the RESILIENT SMA study, taldefgrobep alpha showed clinically meaningful improvements in motor function at all timepoints on the Motor Function Measurement- ...

5. institut-myologie.org institut-myologie.org/en/2025/02/19/sma-clinical-trial-results-whats-new/

SMA clinical trial results: what's new? As several clinical trials continue in SMN1-related proximal spinal muscular atrophy, new results have been shared.

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000205020

Taldefgrobep Alfa in Spinal Muscular Atrophy (P2-11.008) This phase 3 study aims to investigate the efficacy and safety of taldefgropeb as an adjunctive treatment with SMN upregulators in particpants with SMA.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0960896623005618

P04 Taldefgrobep alfa: preclinical and clinical data ... Preclinical data suggest a potential benefit from taldefgrobep plus SMN upregulation in SMA. Along with robust safety data from clinical studies, these results ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10787703/

The Clinical Development of Taldefgrobep Alfa: An Anti ... Modified analyses included all safety data available from the double-blind phase in taldefgrobep alfa-treated patients (AEs reported during the ...