BBP-418, Potential LGMD2i Therapy in Phase 2 Trial, on FDA Fast Track

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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BBP-418, an investigational disease-modifying medication that aims to improve muscle strength and function in people with limb-girdle muscular dystrophy type 2i (LGMD2i), has been given fast track designation by the U.S. Food and Drug Administration (FDA).

This designation aims to facilitate and speed the development and regulatory review of  treatments with the potential to fill an unmet medical need for people with serious conditions.

If approved, BBP-418 — which is now in clinical testing in patients — would become the first therapy for LGMD2i, a rare form of muscular dystrophy caused by mutations in the gene FKRP.

“As of now, there are no approved treatment options for people born with Limb-girdle Muscular Dystrophy Type 2i,” Douglas Sproule, MD, said in a press release. Sproule is chief medical officer at ML Bio Solutions, a subsidiary of BridgeBio Pharma, which is developing BBP-418.

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“We are grateful the FDA has granted our program Fast Track designation … allowing us to potentially deliver our medicine to patients more quickly,” Sproule said.

Mutations in FKRP impair the addition of a specific sugar molecule to a protein called alpha-dystroglycan. This protein normally acts like a “shock absorber” in muscle cells, helping to prevent damage caused by the everyday wear-and-tear of muscle movements. Without alpha-dystroglycan, muscle cells become damaged over time, leading to limb and thoracic (“girdle”) dysfunction.

BBP-418, also called ribitol, is an orally available precursor molecule, or prodrug, that gets converted into a sugar component of alpha-dystroglycan once inside the body. In preclinical experiments conducted in mouse models of LGMD2i, treatment with ribitol restored alpha-dystroglycan levels in muscle cells and led to improvements in muscle function.

ML Bio announced in February that a first patient had been dosed in a Phase 2 clinical trial (NCT04800874) testing ascending doses of oral BBP-418 in up to 16 children and adults with LGMD2i.

This open-label (no placebo group) trial’s main goal is the therapy’s safety and tolerability, with secondary goals assessing its effects on levels of the working version of alpha-dystroglycan and changes to muscle as seen in a muscle biopsy after 27 months (over two years) of treatment.

The Phase 2 study, allowing for at-home as well as on-site treatment, is expected to finish collecting data in October 2023 and conclude in 2026. All enrolled took part in an LGMD2i natural history and biomarker study (NCT04202627) also conducted at Virginia Commonwealth University.

A separate Phase 1 trial in healthy volunteers is also evaluating the investigational medication’s safety, tolerability, and pharmacological properties.

BBP-418 has also been designated an orphan drug in both the U.S. and Europe, a status given to potential treatments of rare diseases that offers financial and other incentives to its developer.