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Atebrioz (zilurgisertib)

Fibrodysplasia ossificans progressiva

Also known as INCB000928
Regulatory submission
NDA submitted by May 2026
Last updated
96 sources

Product information and disease descriptionPlace of product in therapyDisease description

Clinical presentation - signs and symptoms

14 evidence topics · 8 sources

Congenital skeletal malformations: great toes and other anomalies

“Individuals with FOP appear normal at birth except for characteristic malformations of the great toes that are present in all classically affected individuals” (opens the source at this quote in a new tab)

“Other skeletal anomalies associated with FOP include short malformed thumbs with interphalangeal joint fusion, clinodactyly, malformation of the temporomandibular joints, variable and often asymmetric fusions of the costovertebral and costotransverse joints, short broad femoral necks, and osteochondromas, most notably of the proximal medial tibias and femurs, but variably present throughout the normotopic skeleton” (opens the source at this quote in a new tab)

Flare-ups: presenting symptoms, frequency, and triggers

“Major symptoms experienced during a flare-up included swelling (93.1%; 429/461), pain (86.3%; 398/461), decreased movement (78.5%; 362/461), stiffness (72.9%; 336/461), and warmth (15%; 313/461) [Figure 3a].” (opens the source at this quote in a new tab)

“About 71% (341/460) reported at least one flare-up in the previous 12 months. Overall, patients reported an average of 1.9 ± 0.1 flare-ups in the preceding 12 months (median 1.0; range of 0 to 7)” (opens the source at this quote in a new tab)

“Intramuscular immunization was the cause of a flare-up in 25.1% (115/459), which led to bone formation in 84.3% (97/115) of these patients. As many as 61% of all flare-ups occurred spontaneously.” (opens the source at this quote in a new tab)

Heterotopic ossification: anatomic pattern

“FOP HO progresses in characteristic anatomic and temporal patterns with age, typically first occurring in the dorsal, axial, cranial, and proximal regions of the body and later in the ventral, appendicular, caudal, and distal regions.” (opens the source at this quote in a new tab)

“Ribbons, sheets, and plates of heterotopic bone replace skeletal muscles and connective tissues through a process of endochondral ossification that leads to an armament-like encasement of bone and permanent immobility.” (opens the source at this quote in a new tab)

Joint immobility and loss of function after flare-ups

“Among all responders, 96.4% (479/685) reported at least one body region with partial or limited movement.” (opens the source at this quote in a new tab)

“Almost half of survey participants reported that their last flare-up resulted in at least a 50% reduction of mobility around a joint, with 15% reporting a complete loss of movement.” (opens the source at this quote in a new tab)

Pain: during and outside flare-ups

“We observed that although moderate to severe pain (≥4, 0 to 10 pain scale) was commonly associated with flare‐ups (56% to 67%), surprisingly, 30% to 55% of patients experienced similar pain levels during non–flare‐up states.” (opens the source at this quote in a new tab)

“Chronic pain syndromes are common in FOP and may be related to neuropathies (eg, entrapment, nerve damage, allodynia), musculoskeletal origin (eg, back pain, myofascial pain), inflammation, or mechanical/compressive causes (eg, from expanding HO, especially late in the course of a flare-up).” (opens the source at this quote in a new tab)

Respiratory: restrictive chest wall disease and thoracic insufficiency

“Severe restrictive chest wall disease and decrease in pulmonary function due to developmental arthropathy of the costo-vertebral joints and heterotopic ossification of the chest wall develops early” (opens the source at this quote in a new tab)

“Pneumonia or right-sided heart failure may complicate rigid fixation of the chest wall.” (opens the source at this quote in a new tab)

“Restrictive pulmonary function, identified by TLC or suspected by FVC, was found in all, but one, patients.” (opens the source at this quote in a new tab)

“In conclusion, restrictive pulmonary function was found in the majority of patients already at an early age.” (opens the source at this quote in a new tab)

Hearing: conductive hearing impairment

“Conductive hearing impairment is common in FOP through various mechanisms. Fibrodysplasia ossificans progressiva patients should be screened in childhood by audiometry for hearing impairment.” (opens the source at this quote in a new tab)

“In the literature, prevalence is reported between 30.8% and 42%” (opens the source at this quote in a new tab)

“All the patients developed at least a mild hearing loss.” (opens the source at this quote in a new tab)

Jaw ankylosis and nutrition

“Severe weight loss may result following ankylosis of the jaw.” (opens the source at this quote in a new tab)

“In cases of ankylosis of the jaw, a dietician should be consulted to ensure adequate nutrition.” (opens the source at this quote in a new tab)

Spinal deformity

“Spinal deformity is common in FOP and can occur independently of flare-ups.” (opens the source at this quote in a new tab)

“92.5% of total patients had complications, with the highest proportion of complications being spinal deformities (80.6%).” (opens the source at this quote in a new tab)

Renal: kidney stones

“There is a 3-fold greater risk of kidney stones in FOP.” (opens the source at this quote in a new tab)

Neurological: headache and neurological symptoms

“Patients with FOP have reported a higher incidence of neurological symptoms, including pain both during and after an FOP flare-up.” (opens the source at this quote in a new tab)

“Some individuals with FOP report chronic headaches.” (opens the source at this quote in a new tab)

Psychological: anxiety, depression, and irritability

“In those patients reporting pain levels of ≥4, 45% to 74% of patients report experiencing anxiety, depression, or irritability, with 36% to 48% reporting emotional problems during no to mild pain states.” (opens the source at this quote in a new tab)

Gastrointestinal: nausea and vomiting

“Many patients with FOP report frequent nausea and vomiting. The cause and significance of this is unknown.” (opens the source at this quote in a new tab)

System-based symptom burden in the IFOPA registry

“Auditory complaints were the most common and included hearing loss and earaches/drainage. Sleep problems, especially poor sleep quality, and increased sleep latency, were the next most common complaints. Among pulmonary issues reported, difficulty breathing, cough, and respiratory infection were the most prominent conditions. Dermatologic complaints included rash and ulcers. Abdominal pain was the most prevalent gastrointestinal complaint, followed by reflux symptoms and nausea. The most prevalent neurological symptoms were headaches, paresthesias, and neuropathic pain. Flank pain and nephrolithiasis were the most frequent renal/urologic concerns. Menstrual abnormalities were the most common endocrine problem and heart palpitations the most common cardiac issue.” (opens the source at this quote in a new tab)