BBP-418 for limb-girdle muscular dystrophy
Fact-checked by What is BBP-418 for limb-girdle muscular dystrophy?
BBP-418, also known as ribitol, is an experimental oral therapy designed to improve motor function in people with limb-girdle muscular dystrophy type 2i (LGMD2i).
LGMD2i, also known as LGMDR9, is a form of muscular dystrophy that is caused by mutations in the FKRP gene, which contains instructions for cells to manufacture fukutin-related protein (FKRP).
FKRP is responsible for adding sugar molecules to the alpha-dystroglycan protein in a process called glycosylation. This modification allows alpha-dystroglycan to form a complex with other proteins that stabilizes muscle cells and protects them from injury.
In people with LGMD2i, FKRP is present, but it isn’t working at full capacity, so the protective protein complex can’t assemble, and muscles are susceptible to damage. Weakness and wasting in the muscles around the hips and shoulders lead to an abnormal gait and other symptoms.
BBP-418 aims to boost the function of FKRP in the body by providing it with extra amounts of the raw materials it needs to glycosylate alpha-dystroglycan, essentially giving the partially functional enzyme the tools it needs to still get the job done. The resulting protective effects for muscles are expected to stabilize or improve motor function.
Bridgebio Pharma is developing BBP-418, which is currently in Phase 3 clinical testing. The company has indicated plans to submit an application seeking the therapy’s U.S. approval in 2026. BBP-418 holds orphan drug designation in the U.S. and Europe, as well as fast track and rare pediatric disease designations in the U.S., all of which are intended to expedite its clinical development.
Therapy snapshot
| Treatment name | BBP-418 |
| Administration | Oral solution |
| Clinical testing | Currently in Phase 3 testing |
How will BBP-418 be administered in LGMD?
In an ongoing Phase 3 trial, BBP-418 is being administered as an oral solution, at a dose of 9 or 12 grams twice daily, depending on the patient’s body weight. The medication comes in granules that are then dissolved in water to form an oral solution.
BBP-418 in LGMD clinical trials
An ongoing Phase 3 trial called FORTIFY (NCT05775848) is testing the safety and efficacy of twice-daily BBP-418 against a placebo in 112 symptomatic LGMD2i patients, ages 12-60, over a three-year treatment period. Top-line, one-year data showed:
- BBP-418 led to statistically significant and clinically meaningful improvements in walking function compared with the placebo. Participants in the BBP-418 group were able to walk, on average, 0.14 m/s more quickly than they had before the study’s start, whereas the average walking speed decreased by about the same amount in the placebo group. The data translate to patients on BBP-418 being able to walk 100 meters about 14 seconds faster than those on the placebo.
- Forced vital capacity, a measure of lung function, also improved with BBP-418 while worsening in the placebo group.
- Glycosylated alpha-dystroglycan increased significantly, and creatine kinase, a marker of muscle damage, decreased significantly with BBP-418.
FORTIFY is expected to finish in 2027.
An ongoing open-label Phase 2 trial called MLB-01-003 (NCT04800874) has also demonstrated the clinical benefits of BBP-418 for LGMD2i. The study enrolled 14 participants, ages 12-55, with moderate or severe disease. The data showed that BBP-418 increased participants’ walking speed, with the benefits lasting for more than a year. It also led to increases in glycosylated alpha-dystroglycan levels and decreases in creatine kinase.
The long-term extension part of the study is ongoing and is expected to conclude in late 2026.
BBP-418 side effects
Clinical trials of BBP-418 are still ongoing, so its safety profile in LGMD2i is not fully established. In a Phase 2 study, treatment-related side effects with BBP-418 included:
- diarrhea
- nausea
- vomiting
- bloating
- dehydration
- indigestion
- inflammation of the stomach and intestines
- headaches
- stomach pain
Interim safety results in the Phase 3 FORTIFY study were consistent with these Phase 2 findings. No serious safety concerns related to treatment had been reported after one year of treatment.
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