The US Food and Drug Administration approved garetosmab-grts (Pasatru) for adults with fibrodysplasia ossificans progressiva to reduce the formation of new heterotopic ossification lesions and clinician-assessed flare-ups, according to a press release from Regeneron Pharmaceuticals. The recommended starting dose is 10 mg/kg based on weight, administered intravenously over 60 minutes every 4 weeks. The dose may be reduced to 3 mg/kg, administered over 60 minutes every 4 weeks, if the starting dose is not tolerated.
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder in which heterotopic bone progressively forms in muscles, tendons, ligaments, and other connective tissues. Heterotopic ossification (HO) involving the jaw, spine, hips, and rib cage can impair speaking, eating, walking, and breathing and contribute to progressive loss of mobility. Approximately 900 patients worldwide have been diagnosed with FOP.
The FDA based the approval on efficacy and safety findings from the phase 3 OPTIMA trial. The trial enrolled 63 adults with an FOP-causing variant of type I activin A receptor, evidence of FOP disease activity or HO progression, and a cumulative analogue joint involvement scale score of 19 or lower. Participants were randomly assigned to receive intravenous garetosmab 10 mg/kg, garetosmab 3 mg/kg, or placebo every 4 weeks for 56 weeks. Efficacy assessments included whole-body computed tomography for HO lesions, physician and patient assessments of flare-ups, joint function, and changes in disease severity.
At week 56, patients who received garetosmab 10 mg/kg had 2 new HO lesions compared with 19 among patients who received placebo, representing a 90% reduction. Patients who received garetosmab 3 mg/kg had 1 new HO lesion, representing a 94% reduction compared with placebo. Clinician-assessed flare-ups totaled 9 in the 10-mg/kg group, 53 in the 3-mg/kg group, and 66 in the placebo group, corresponding to reductions of 88% and 15%, respectively. The proportion of patients who reported flare-ups through week 56 did not differ significantly between treatment and placebo groups.
Serious treatment-emergent adverse events occurred in 2 patients who received garetosmab 10 mg/kg, 1 who received 3 mg/kg, and 2 who received placebo. Adverse reactions reported in at least 10% of garetosmab-treated patients included abscess, acne, increased hair growth, madarosis, oral ulcers, epistaxis, folliculitis, paronychia, and rash. Garetosmab can cause serious birth defects when administered during pregnancy as well as skin and soft tissue infections and epistaxis. Patients who are pregnant should not receive garetosmab.
Source: Regeneron Pharmaceuticals Inc.
