Bridgebio looks to lead limb girdle pipeline

Should a phase 3 trial of Bridgebio’s BBP-418 start later this year, as the company hopes, this will become the first novel asset for limb girdle muscular dystrophy to make it into pivotal testing. LGMD is a diverse group of muscle wasting disorders caused by various inherited genetic malfunctions, which cause a wide spectrum of disease progression and severity – characteristics that make drug development incredibly tough. BBP-418 targets one of the more common subtypes, 2I. Pfizer’s anti-myostatin MAb domagrozumab was trialled by academics here, without success, as was PTC’s Emflaza, a steroid product sold for Duchenne muscular dystrophy. Gene therapy approaches now dominate, largely thanks to Sarepta, which bought into the space via its 2019 acquisition of Myonexus. Progress with a project targeting LGMD 2E triggered that deal, though the phase 1 study of SRP-9003 has since completed. Work does not seem to have progressed much further, on ‘9003 or elsewhere, although Sarepta is sponsoring a natural history study in a couple of other subtypes. Given ongoing concerns about AAV gene therapy approaches, it is encouraging to see a new mechanism in BBP-418 progress through the pipeline; perhaps success will encourage much-needed new approaches in other LGMD subtypes. 

A wide target? The limb girdle muscular dystrophy pipeline 
Project Company  LGMD type (genetic target) Mechanism  Study details
BBP-418  Bridgebio Type 2I (FKRP) Glycosylation substrate (small molecule)  Ph2 ongoing; ph3 to start YE 2022
LION-101  Bayer (Asklepios) Type 2I (FKRP) AAV gene therapy  Ph1 due to start 2022
ATA-100 Atamyo Type 2I (FKRP) AAV gene therapy Ph1/2 to start shortly 
SRP-9003 Sarepta Type 2E (β-sarcoglycan) AAV gene therapy  Ph1/2 trial complete; exploratory trial ongoing 
SRP-9004 Sarepta Type 2D (α-sarcoglycan) AAV gene therapy  Ph1 conducted by academic partner completed 
SRP-6004 Sarepta Type 2B (Dysferlin) AAV gene therapy Ph1 conducted, status unclear 
SRP-9005 Sarepta Type 2C (γ-sarcoglycan) AAV gene therapy Preclinical
SRP-9006 Sarepta Type 2L (Anoctamin 5) AAV gene therapy Preclinical 
Calpain 3  Sarepta Type 2A (Calpain) AAV gene therapy Preclinical 
Source: Evaluate Pharma & company statements. 

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