Clinical Trials for SMA

Intro

While three treatments for SMA are currently available in most European countries, a critical need for ongoing research into new therapies remains.

A key challenge is that existing treatments may not be equally effective for all individuals with SMA. Continued drug development and clinical trials are essential to offer improved treatment options and, ultimately, a cure.

Current available treatments might still be studied in clinical trials, to explore different conditions such as different dosages, frequencies, patient population, or to test them in combination with other treatments.

New potential therapies have reached clinical trial stages and show promise in treating SMA.

Combination Therapy

In focus

There are different approaches used to develop treatments for SMA (see also table below)

1. Treatments aimed at enhancing SMN protein production (disease-modifying treatments):

Replacement of the SMN1 gene (approach called “gene therapy”), to increase production of a functional SMN protein. This is the mechanism of action of onasemnogene abeparvovec-xioi (Zolgensma) and OAV101 IT.
Enhancement of the SMN2 gene, to increase production of full length, functional SMN protein, as done by nusinersen (Spinraza), risdiplam (Evrysdi), salanersen (BIIB115)

2. SMN-independent strategies:

Enhancement of muscle growth and strength, as done by apitegromab, taldefgrobep alfa, GYM329.
Enhancement of muscle function by increasing muscle contractions, as done by NMD-670.
Use of medical devices to improve motor function, such as the spinal cord stimulator studied by Dr. Capogrosso’s team. The study is co-funded by our SMArt Horizon Initiative.
Strategies targeting the neuromuscular junctions, as planned by argenx.

3. Combination strategies

In addition, combinations of approaches are being explored, such as improving SMN2 gene function together with enhancement of muscle strength.

Further approaches are currently being explored in pre-clinical development.

: <a href="/novartis-gene-therapies">Onasemnogene abeparvovec-xioi (Zolgensma) - Novartis</a>
Approach :: SMN-dependent (DMT, Disease Modifying Therapies)
Mechanism of action:: SMN1 gene replacement (SMN protein increase)
Drug type:: Gene therapy
Delivery method:: Intravenous injection
Stage:: Approved

: <a href="/oav-101">OAV101 IT - Novartis</a>
Approach :: SMN-dependent (DMT, Disease Modifying Therapies)
Mechanism of action:: SMN1 gene replacement (SMN protein increase)
Drug type:: Gene therapy)
Delivery method:: Intrathecal injection
Stage:: Clinical trials

: <a href="/roche">Risdiplam (Evrysdi) – Roche</a>
Approach :: SMN-dependent (DMT, Disease Modifying Therapies)
Mechanism of action:: SMN2 splicing modifier (SMN protein increase)
Drug type:: Small molecule
Delivery method:: Oral
Stage:: Approved

: <a href="/biogen">Spinraza (Nusinersen) - Biogen</a>
Approach :: SMN-dependent (DMT, Disease Modifying Therapies)
Mechanism of action:: SMN2 splicing modifier (SMN protein increase)
Drug type:: Antisense oligonucleotide
Delivery method:: Intrathecal injection
Stage:: Approved

: <a href="/biib-115">Salanersen (BIIB115) - Biogen</a>
Approach :: SMN-dependent (DMT, Disease Modifying Therapies)
Mechanism of action:: SMN2 splicing modifier (SMN protein increase)
Drug type:: Antisense oligonucleotide
Delivery method:: Intrathecal bolus injection
Stage:: Clinical trials

: <a href="/scholar-rock">Apitegromab (SRK-015) - Scholar Rocks</a>
Approach :: SMN independent
Mechanism of action:: Anti-myostatin (Muscle enhancement)
Drug type:: Antibody
Delivery method:: Intravenous injection
Stage:: Clinical trials

: <a href="/taldefgrobep-alfa">Taldefgrobep alfa – Biohaven</a>
Approach :: SMN independent
Mechanism of action:: Anti-myostatin (Muscle enhancement)
Drug type:: Fully human recombinant protein
Delivery method:: Subcutaneous injection
Stage:: Clinical trials

: <a href="/gym-329">GYM329 - Roche</a>
Approach :: SMN independent
Mechanism of action:: Anti-myostatin (Muscle enhancement)
Drug type:: Antibody
Delivery method:: Subcutaneous injection
Stage:: Clinical trials

: <a href="/nmd-670">NMD-670 - NMD Pharma</a>
Approach :: SMN independent
Mechanism of action:: ClC-1 (skeletal muscle-specific chloride channel) inhibitor (Neuromuscular transmission enhancement)
Drug type:: Small molecule
Delivery method:: Oral
Stage:: Clinical trials

: <a href="/spinal-cord-stimulator">Spinal Cord Stimulator</a>
Approach :: SMN independent
Mechanism of action:: Spinal cord electrical stimulation
Drug type:: Medical device (electrodes)
Delivery method:: Implantation of electrodes
Stage:: Clinical trials

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