The US Food and Drug Administration (FDA) has approved Pasatru (garetosmab-grts) to reduce formation of new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in adults with fibrodysplasia ossificans progressiva (FOP).
FOP is a disorder in which skeletal muscle and connective tissue are gradually ossified. This condition leads to bone formation outside the skeleton that restricts movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and moving down the body and into the limbs. People with FOP are born with abnormal big toes which can be helpful in making the diagnosis. Trauma, such as a fall or invasive medical procedure, or a viral illness may trigger episodes of muscle swelling and inflammation. These flareups last for several days to months and often result in permanent bone growth in the injured area. FOP is almost always caused by a genetic change at the same place in the ACVR1 gene.
Garetosmab is a VelocImmune-derived, fully human monoclonal antibody that blocks Activin A, a protein critical to the development of HO lesions in patients with FOP. The approval is based on safety and efficacy data from the phase 3 OPTIMA clinical trial (NCT05394116) evaluating garetosmab in adults (18 years and older) with FOP.
At 56 weeks, both doses of garetosmab, 10 mg/kg and 3 mg/kg, met the primary endpoint and significantly reduced the total number of new HO lesions as compared to placebo, demonstrating a 90% and 94% reduction, respectively, as assessed by computed tomography (CT) scan. The number of clinician-assessed flare-ups during this time were 9 in the garetosmab 10 mg/kg group, 53 in the garetosmab 3 mg/kg group, and 66 in the placebo group. Changes in the proportion of patients with patient-reported flare-ups through week 56 were not significantly different between placebo and treatment groups.
Of the 63 people who participated in the trial, serious treatment-emergent adverse events occurred in 2 patients treated with 10 mg/kg garetosmab, 1 patient treated with 3 mg/kg garetosmab, and 2 patients treated with placebo. The most common adverse reactions occurring were abscess, acne, increased hair growth, madarosis, oral ulcers, epistaxis, folliculitis, paronychia, and rash.
The recommended starting dosage is 10 mg/kg infusions once monthly but may be decreased to a 3 mg/kg infusions once monthly if the higher dose is not well tolerated.
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To learn more about FOP and other are musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/