Limb-girdle muscular dystrophy R9 (LGMDR9) is caused by a deficiency of FKRP. FKRP allows the addition of ribitol-5-phosphate, a molecule made from ribitol, to the sugar chain already formed by the action of other enzymes. Oral intake of BBP-418 (ribitol) is intended to increase glycosylation of α-dystroglycan by saturating FKRP with substrate. A Phase I (completed) and Phase II (ongoing) trial of ribitol have delivered initial results.
• The Phase 1 trial was conducted in 85 healthy volunteers. This randomized controlled trial of a single dose and then multiple escalating doses versus placebo studied the pharmacokinetics of the molecule, and found it to be very well tolerated with no signs of toxicity even at doses above the intended therapeutic doses.
• A Phase 2 open-label trial of BBP-418 in 14 people with LGMDR9, aged 12 to 55 years, is designed to determine the safety and tolerability of escalating doses of BBP-418 over 5 years.
Preliminary results in the first 12 participants, aged 12 to 53 years, 9 of whom had retained walking, were presented at the Muscular dystrophy association (MDA) 2022 conference. They show:
- a 43% increase in glycosylated alpha-dystroglycan ;
- a mean decrease in CPK at 90 days of 70%;
- an increase in the walking speed over 10 meters at 3 and 6 months, whereas it had decreased in the 6 months of natural history study preceding the intake of ribitol.
Based on these encouraging preliminary results, BridgeBio, the company developing this drug candidate, plans to launch a Phase III trial in the second half of 2022.
