ISEMBYLD™
ISEMBYLD™ is an FDA-approved prescription medicine used to treat spinal muscular atrophy (SMA) in adults and children 2 years of age and older who are currently receiving a survival motor neuron 2 (SMN2)-targeted treatment. It is the first FDA-approved treatment for those living with SMA to directly target the muscle.
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ISEMBYLD™
- ISEMBYLD™ (apitegromab-mstn) is FDA-approved for the treatment of spinal muscular atrophy (SMA) in adults and children two years of age and older who are currently receiving a survival motor neuron 2 (SMN2)-targeted treatment.
- ISEMBYLD 10 mg/kg is administered once every 4 weeks as an intravenous (IV) infusion by a healthcare professional at an infusion center, hospital, or at home.
- ISEMBYLD dosing is calculated by weight.
- Scholar Rock Supports™ offers programs and resources designed to provide support for eligible patients and families in the United States, including:
- Help understanding and navigating insurance coverage,
- Financial assistance for eligible patients, and
- Educational materials regarding the treatment process and disease state.
- For the most up-to-date prescribing information, see here.
Overview:
| Description | Recombinant monoclonal antibody |
| Mechanism | Pro and latent myostatin inhibitor |
| Approved age | Adults and children 2 years of age and older |
| Dose | 10mg/kg |
| How given | Intravenous infusion over approximately 60 minutes to 120 minutes at an infusion rate no greater than 150 mL/hour |
| How often | Once every 4 weeks. If a planned dose is missed, it is recommended to administer ISEMBYLD as soon as possible and then restart the dosing schedule 4 weeks after the missed dose is administered. Alternatively, if a planned dose is missed, dosing may be resumed on the next scheduled dose to maintain the original dosing schedule. |
| Warnings and precautions | ISEMBYLD may increase the risk of fractures, including serious fractures. In SAPPHIRE, 5/53 (9%) of patients treated with ISEMBYLD 10 mg/kg and 3/53 (6%) of patients treated with ISEMBYLD 20 mg/kg (twice the recommended dosage) experienced fractures compared with one patient in the placebo group (2%) who had a fracture. Femur fractures occurred in three patients treated with ISEMBYLD in Study 1. No patients discontinued treatment due to fractures. In an ongoing open-label extension study in which patients received ISEMBYLD 20 mg/kg (twice the recommended dosage), fractures occurred in 22 patients (9%), including 5 serious events of femur fractures. Most patients with fractures had histories of low bone density previous fractures, or contractures. Some fracture events did not have a clear precipitating event (such as a fall). |
| Adverse reactions | The most common adverse reactions (reported in at least 20% of patients treated with ISEMBYLD and more frequently than in placebo) were upper respiratory tract infections, vomiting, cough, other viral infections, headache, gastroenteritis, pharyngitis, and hypersensitivity. Call your healthcare provider for medical advice about side effects. |
| Drug Interactions | An effect of apitegromab-mstn on the pharmacokinetics (PK) of co-administered medications is not expected. Based on the population PK analysis, SMN-modulating therapies (nusinersen and risdiplam) had no effect on apitegromab-mstn PK in patients with SMA. |
| Use in Specific Populations | Pregnancy: There are no adequate data on the developmental risk associated with the use of ISEMBYLD in pregnant women. Monoclonal antibodies, such as apitegromab-mstn, are known to cross the placental barrier with a higher likelihood of fetal exposure with administration during the third trimester; therefore, apitegromab-mstn may be transported from the mother to the fetus across the placenta during the pregnancy.
Breastfeeding: There are no data on the presence of apitegromab-mstn in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Maternal IgG is known to be present in human milk, and the potential for absorption of ISEMBYLD to lead to inhibition of myostatin activation in the breastfed infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ISEMBYLD, and any potential adverse effects on the breastfed infant from ISEMBYLD, or from the underlying maternal condition. |
| Prescribing information | See here.(opens in new tab) |
History of ISEMBYLD™
In 2015, Scholar Rock’s foundational expertise in selective growth factor targeting led to the identification of a monoclonal antibody with the ability to target the latent, precursor form of myostatin, a signaling protein that regulates muscle growth. Scholar Rock believed their highly-selective muscle-targeted approach could address key unmet needs raised by the SMA community around the need for muscle strength and motor function. Following significant preclinical investigation, which confirmed the potential of a muscle-targeted approach in SMA, Scholar Rock launched a series of clinical trials of ISEMBYLD™ beginning in 2018.
FDA approval of ISEMBYLD (apitegromab-mstn) was based on the SAPPHIRE clinical trial, a randomized, double-blind, placebo-controlled study that evaluated the safety and efficacy of ISEMBYLD in nonambulatory patients with Types 2 and 3 SMA who were receiving either nusinersen or risdiplam. The Phase 3 SAPPHIRE trial met its primary endpoint, with ISEMBYLD 10mg/kg demonstrating clinically meaningful improvements on HFMSE. It was further informed by data from the Phase 2 TOPAZ proof-of-concept trial and the open-label, multicenter ONYX extension study, which together offer more than 4 years of data for ISEMBYLD.