What is the mechanism of action of this treatment?

The most common treatments for Spinal Muscular Atrophy (SMA) include gene therapy and antisense oligonucleotides. Gene therapy, such as onasemnogene abeparvovec, works by delivering a functional copy of the SMN1 gene to motor neurons, thereby increasing the levels of the essential SMN protein. Antisense oligonucleotides, like nusinersen, modify the splicing of the SMN2 gene to produce more functional SMN protein. These treatments are significant for SMA patients as they address the underlying genetic cause of the disease, leading to potential improvements in motor function and overall survival.

What side effects are associated with this type of intervention?

The most common treatments for Spinal Muscular Atrophy (SMA) include nusinersen (Spinraza) and onasemnogene abeparvovec (Zolgensma). Nusinersen, administered intrathecally, can cause side effects such as respiratory infections, constipation, and post-lumbar puncture syndrome. Onasemnogene abeparvovec, a gene therapy, may lead to elevated liver enzymes, vomiting, and thrombocytopenia. Both treatments require careful monitoring for potential adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Spinal Muscular Atrophy (SMA), including nusinersen, onasemnogene abeparvovec, and risdiplam. Nusinersen, marketed as Spinraza, is an antisense oligonucleotide that modifies SMN2 gene splicing to increase the production of functional SMN protein. Onasemnogene abeparvovec, known as Zolgensma, is a gene replacement therapy that delivers a functional copy of the SMN1 gene via an adeno-associated virus vector. Risdiplam, sold under the brand name Evrysdi, is an oral medication that also targets SMN2 gene splicing to boost SMN protein levels. These treatments have shown significant efficacy in improving motor function and survival in SMA patients.

What other types of research exist?

One promising novel alternative for Spinal Muscular Atrophy (SMA) patients is the use of OAV101 administered intrathecally. This treatment is currently being evaluated in a Phase IIIb, open-label, multi-center study for its safety, tolerability, and efficacy in patients who have discontinued treatment with Nusinersen or Risdiplam. This approach may offer a viable long-term treatment option for SMA patients.

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Gene Therapy

OAV101 for SMA (STRENGTH Trial)

Phase 3

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

SMA diagnosis

Aged 2 to 12 years

Must not have

Contraindications for lumbar puncture procedure

At Baseline, participants are excluded if they received nusinersen (Spinraza®) or risdiplam (Evrysdi®) within a defined timeframe

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 52 weeks

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial tests a gene therapy given as an injection into the lower back in children who haven't used certain other treatments. The therapy works by using a virus to deliver a healthy gene to their cells.

Who is the study for?

This trial is for children aged 2 to 12 with Spinal Muscular Atrophy (SMA) who have previously been treated with nusinersen or risdiplam but stopped. They must show SMA symptoms and not have high antibody levels against AAV9, significant test abnormalities, contraindications for spinal taps, recent vaccinations, hospitalizations for pulmonary events or surgeries planned.

What is being tested?

The study tests OAV101's safety and effectiveness in treating SMA when given through a spinal injection. It involves one treatment day followed by a year of follow-up. Participants are divided into two age groups: 2-5 years old and 6-12 years old.

What are the potential side effects?

Potential side effects aren't specified here but may include reactions related to the immune system due to antibodies against AAV9 or complications from the lumbar puncture procedure.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with Spinal Muscular Atrophy (SMA).

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I am between 2 and 12 years old.

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I have received at least four doses of Spinraza or been on Evrysdi for 3 months.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot have a lumbar puncture due to health reasons.

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I have not taken Spinraza or Evrysdi recently.

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I was hospitalized for lung problems or needed nutritional support recently.

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I currently have an infection or a fever.

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I need a machine to help me breathe.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 52 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~52 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 52 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number and percentage of participants reporting AEs, related AEs, SAEs, and AESIs

Secondary study objectives

Change from baseline to Week 52 visit in Assessment of Caregiver Experience in ACEND instrument score

Change from baseline to Week 52 visit in the HFMSE total score

Change from baseline to Week 52 visit in the RULM total Score

Side effects data

From 2023 Phase 4 trial • 16 Patients • NCT05073133

44%

Pyrexia

44%

Vomiting

31%

Alanine aminotransferase increased

31%

Aspartate aminotransferase increased

31%

Gamma-glutamyltransferase increased

25%

Cough

25%

Platelet count decreased

19%

Bronchiolitis

19%

Influenza

19%

Respiratory tract infection

19%

Hepatic enzyme increased

13%

Bilirubin conjugated increased

13%

Blood lactate dehydrogenase increased

13%

Transaminases increased

13%

Blood alkaline phosphatase increased

13%

Rhinorrhoea

13%

Upper respiratory tract congestion

13%

Gastroenteritis

13%

Irritability

13%

Viral infection

13%

Diarrhoea

13%

Thrombotic microangiopathy

13%

COVID-19

13%

Catarrh

13%

Tonsillitis

Rhinitis

Rash

Coxsackie viral infection

Pneumonia

Constipation

Subcutaneous emphysema

Hepatic failure

Thrombocytopenia

White blood cell count increased

Hypoglycaemia

Upper respiratory tract infection

Nausea

Decreased appetite

Renal failure

Femur fracture

Salivary hypersecretion

Laryngitis

Pneumonia aspiration

Asymptomatic bacteriuria

Hypersensitivity

Pneumonia bacterial

Conjunctivitis

Stomatitis

Urinary tract infection

100%

80%

60%

40%

20%

Study treatment Arm

OAV101A1 1.le 14vg/kg All

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: OAV-101Experimental Treatment1 Intervention

Intrathecal administration of OAV101 at a dose of 1.2 x 10\^14 vector genomes, one time dose

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

OAV101

2021

Completed Phase 4

~40

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Spinal Muscular Atrophy (SMA) include gene therapy and antisense oligonucleotides. Gene therapy, such as onasemnogene abeparvovec, works by delivering a functional copy of the SMN1 gene to motor neurons, thereby increasing the levels of the essential SMN protein. Antisense oligonucleotides, like nusinersen, modify the splicing of the SMN2 gene to produce more functional SMN protein. These treatments are significant for SMA patients as they address the underlying genetic cause of the disease, leading to potential improvements in motor function and overall survival.