Isembyld (apitegromab-mstn) for spinal muscular atrophy
Fact-checked by What is Isembyld for spinal muscular atrophy?
Isembyld (apitegromab-mstn) is an approved infusion therapy that’s used as an add-on treatment to help strengthen muscles and improve motor function in people with spinal muscular atrophy (SMA), ages 2 and older.
In SMA, a lack of the SMN protein causes the specialized nerve cells that control movement to sicken and die, leading to progressive muscle weakness and wasting. Standard disease-modifying therapies work to slow disease progression by increasing the levels of SMN.
Isembyld is an add-on treatment designed to help prevent muscle loss in people taking these other SMA therapies. It targets the muscle protein myostatin, which normally inhibits muscle growth to maintain balanced, healthy muscle mass. Apitegromab, the active ingredient in Isembyld, is an antibody that binds to an inactive myostatin precursor, preventing its conversion into active myostatin.
By removing these natural brakes on muscle growth, Isembyld is expected to help preserve muscle mass and improve motor function in people with SMA when used alongside medications that target the underlying cause of the disease.
Isembyld was developed by Scholar Rock and is given via into-the-vein (intravenous) infusions.
Therapy snapshot
| Brand name | Isembyld |
| Chemical name | Apitegromab-mstn |
| Usage | Used as an add-on therapy to help strengthen muscles and improve motor function in people with SMA |
| Administration | Intravenous infusion |
Who can take Isembyld?
Isembyld is approved in the U.S. for the treatment of children and adults with SMA, ages 2 and older, who are currently receiving an SMN2-targeted disease-modifying treatment.
There are no known contraindications, or specific reasons not to use the medication.
How is Isembyld administered?
Isembyld is administered once every four weeks via an intravenous infusion lasting about one to two hours, at a recommended dose of 10 mg per kilogram of body weight.
The infusions may be given at an infusion center, hospital, or at home, depending on patient eligibility, but must always be administered by a trained healthcare provider.
Isembyld in clinical trials
The U.S. approval of Isembyld was primarily supported by data from the Phase 3 SAPPHIRE trial (NCT05156320), which enrolled 188 people with SMA type 2 or 3, ages 2 to 21, who were unable to walk. All were already receiving either Evrysdi (risdiplam) or Spinraza (nusinersen), two approved SMA therapies.
Participants received Isembyld — at its recommended dose (10 mg/kg) or double the recommended dose (20 mg/kg) — or a placebo once every four weeks for about a year. Investigators evaluated changes in the scores of the Hammersmith Functional Motor Scale Expanded (HFMSE), a standard tool used to assess motor function and disease progression in SMA. Results showed that:
- Isembyld significantly improved HFMSE scores relative to the placebo after a year in children ages 2 to 12, meeting the study’s main goal
- significantly more children on Isembyld achieved a clinically meaningful improvement of at least 3 points on the HFMSE than in the placebo group
Although the higher dose of Isembyld did tend to have motor benefits among participants of any age, this dose was not found to be better than the lower dose, and it is thus not recommended on the prescribing label.
Isembyld side effects
The most common side effects of Isembyld include:
- upper respiratory tract infection
- vomiting
- cough
- headache
- other viral infections
- stomach bug (gastroenteritis)
- sore throat (pharyngitis)
- immune reactions (hypersensitivity)
Isembyld also comes with a warning that it may increase the risk of serious bone fractures, so the medication should be used with caution in people with a history of low bone density or multiple fractures. If fractures occur, the benefits and risks of continuing treatment should be considered.
Although there is little available data in humans, animal studies suggest that Isembyld could cause fetal harm if used during pregnancy, and may also affect fertility in males and females. Patients should discuss these matters with their healthcare providers.
SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
