Brand Name
Modeyso
Generic Name
Dordaviprone
View Brand Information FDA approval date: August 06, 2025
Form: Capsule
What is Modeyso (Dordaviprone)?
MODEYSO is indicated for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. MODEYSO is a protease activator indicated for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
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Brand Information
MODEYSO (dordaviprone)
1INDICATIONS AND USAGE
MODEYSO is indicated for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.
This indication is approved under accelerated approval based on overall response rate and duration of response
2DOSAGE FORMS AND STRENGTHS
Capsules: 125 mg, white, opaque, hard capsules printed with “DDP” and “125” on the body and “CMRX” on the cap of the capsule. Each capsule contains 125 mg dordaviprone.
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
The following potential clinically significant adverse reactions are described elsewhere in the labelling:
- Hypersensitivity
- QTc Interval Prolongation
4.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in WARNINGS AND PRECAUTIONS and below reflects exposure to MODEYSO at the recommended weight-based dose taken until disease progression or unacceptable toxicity in 376 adult and pediatric patients with glioma across four open-label clinical studies (ONC006, ONC013, ONC014, and ONC018)
Of the 376 patients who received MODEYSO, 35% were exposed for 6 months, and 17% were exposed for 1 year.
The median age was 23 years (range: 3 to 80): 30% were 2 to 11 years old, 11% were 12 to 17 years old, 55% were 18 to 64 years old, and 3.7% were 65 years or older. Fifty-two percent (52%) were female; 74% White, 10% unknown race or race not reported, 9% Black or African American, 4% Asian, 2.9% other or multiple races; and 13% were of Hispanic or Latino ethnicity. Karnofsky/Lansky Performance Status (KPS/LPS) score was 80 to 100 in 66% of patients, 60 to 70 in 27%, and <60 in 7%.
Relevant disease characteristics included primary tumor locations in the midline (91%) and non‑midline regions (9%); 33% had diffuse intrinsic pontine glioma (DIPG); 30% had multifocal disease; 79% had an H3 K27M mutation; 75% had recurrent disease.
Serious adverse reactions occurred in 33% of patients who received MODEYSO. Serious adverse reactions in >2% of patients included hydrocephalus (5%), vomiting (4.3%), headache (3.2%), seizure (2.4%), and muscular weakness (2.1%). Fatal adverse reactions occurred in 1% of patients who received MODEYSO, including cardiac arrest (0.5%), intracranial hemorrhage (0.3%), and encephalopathy (0.3%).
Permanent discontinuation of MODEYSO due to an adverse reaction occurred in 2.1% of patients. Adverse reactions which resulted in permanent discontinuation of MODEYSO in >1 patient included confusional state.
Dosage interruptions of MODEYSO due to an adverse reaction occurred in 6% of patients. Adverse reactions which required dosage interruption in >1 patient included increased alanine aminotransferase, increased aspartate aminotransferase, decreased lymphocyte count, muscular weakness, and aspiration pneumonia.
Dose reductions of MODEYSO due to an adverse reaction occurred in 2.7% of patients. Adverse reactions which required dose reductions in >1 patient included decreased neutrophil count and increased alanine aminotransferase.
The most common adverse reactions (≥20%) were fatigue, headache, vomiting, nausea, and musculoskeletal pain. The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased calcium, and increased alanine aminotransferase.
Adverse reactions that occurred in at least 10% of patients treated with MODEYSO are presented in Table 4.
a. Includes asthenia.
b. Includes head discomfort and sinus headache.
c. Includes accessory nerve disorder, auditory nerve disorder, facial nerve disorder, facial paralysis, facial paresis, glossopharyngeal nerve disorder, hypoglossal nerve disorder, IIIrd nerve disorder, IIIrd nerve paralysis, IVth nerve disorder, IVth nerve paralysis, tongue paralysis, trigeminal nerve disorder, trigeminal neuralgia, VIth nerve disorder, VIth nerve paralysis, and VIth nerve paresis.
d. Includes back pain, pain in extremity, arthralgia, neck pain, non-cardiac chest pain, myalgia, bone pain, musculoskeletal chest pain, musculoskeletal stiffness, and spinal pain.
e. Includes dermatitis, dermatitis acneiform, dermatitis bullous, eczema, erythema multiforme, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, and rash pustular.
Other clinically important adverse reactions observed in less than 10% of patients treated with MODEYSO were peripheral neuropathy, seizure, diarrhea, tremor, and venous thromboembolic events.
Selected laboratory abnormalities that occurred in at least 10% of patients treated with MODEYSO are presented in Table 5.
a. Severity as defined by the National Cancer Institute CTCAE Version 5.0.
b. The denominator for each laboratory parameter is based on the number of patients with a baseline and post‑treatment laboratory value available, which ranged from 325 to 330 patients.
5DESCRIPTION
Dordaviprone is a protease activator.
Dordaviprone is present as dordaviprone hydrochloride with the molecular formula C
Dordaviprone hydrochloride has the following chemical structure:
Dordaviprone hydrochloride is a white to off-white solid that is freely soluble in water. The 1% solution of dordaviprone hydrochloride is measured as pH 3.3.
MODEYSO (dordaviprone) capsules are supplied as 125 mg strength capsules in an immediate‑release oral formulation. Each MODEYSO capsule contains 125 mg of dordaviprone (equivalent to 148.8 mg of dordaviprone hydrochloride).
The inactive ingredients in the capsule include magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The capsule shell consists of hypromellose and titanium dioxide. The black printing ink contains alcohol, D&C yellow #10, FD&C blue #1, FD&C blue #2, FD&C red #40, ferrosoferric oxide, methyl alcohol,
6CLINICAL STUDIES
The efficacy of MODEYSO was evaluated in adult and pediatric patients with glioma across five open‑label, non-randomized clinical studies conducted in the U.S. (ONC006 [NCT02525692], ONC013 [NCT03295396], ONC014 [NCT03416530], ONC016 [NCT05392374], and ONC018 [NCT03134131]). Pre-specified criteria were defined to establish an integrated efficacy population; eligible patients were required to have received single-agent MODEYSO, have diffuse midline glioma harboring an H3 K27M mutation with progressive and measurable disease per Response Assessment in Neuro-Oncology-High Grade Glioma (RANO-HGG) criteria, be ≥90 days post‑radiation therapy, have adequate washout from prior anticancer therapies, have a Karnofsky Performance Status/Lansky Performance Status (KPS/LPS) score ≥60, and have stable or decreasing corticosteroid use. Patients with diffuse intrinsic pontine glioma (DIPG), primary spinal tumors, atypical histologies, or cerebrospinal fluid dissemination were excluded. Patients received weight-based dosing of MODEYSO until disease progression or unacceptable toxicity.
The integrated efficacy population included 50 patients who met these criteria. The major efficacy outcome measure was overall response rate (ORR) assessed by blinded independent central review (BICR) according to RANO 2.0 criteria. Additional efficacy outcome measures were BICR-assessed ORR according to RANO-HGG criteria and Response Assessment in Neuro-Oncology-Low Grade Glioma (RANO-LGG) criteria, duration of response, and time to response.
Baseline demographics were: median age 31 years (range: 9 to 70) with 6% younger than 17 years of age; 46% female; 80% White, 6% Black or African American, 2% Asian, 10% other races, and 2% race unknown; 8% were of Hispanic or Latino ethnicity; 72% had KPS/LPS 80 to 100. Relevant disease characteristics included 72% treated at first recurrence, 28% had 2 or more recurrences; primary tumor location was thalamic in 52% and non-thalamic midline region in 48%; 88% received prior temozolomide; 62% were receiving corticosteroids at baseline; median time from end of prior radiation was 7.4 months (range: 3.0 to 102.1).
Efficacy results are shown in Table 8.
Abbreviations: BICR=blinded independent central review; CI=confidence interval; RANO=Response Assessment in Neuro-Oncology.
a. Confirmed overall response rate assessed by BICR; CI based on Clopper-Pearson method.
b. Based on Kaplan-Meier estimate.
c. Based on observed time.
Among responders, the median time to response was 3.6 months (range 1.6, 15.6).
Using BICR-assessed RANO 2.0 criteria, there was one additional responder based on the integrated response assessment, which takes into account corticosteroid use and performance status. Based on BICR-assessed RANO-HGG criteria (n=50), the ORR was 20% (95% CI: 10, 34), with 1 complete and 9 partial responses. Based on BICR-assessed RANO-LGG criteria (n=50), the ORR was 20% (95% CI: 10, 34), with 5 partial and 5 minor responses.
7HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
8PATIENT COUNSELING INFORMATION
Advise the patient and caregiver to read the FDA-approved patient labeling (
Hypersensitivity
Advise patients that MODEYSO can cause hypersensitivity. Inform patients about the signs and symptoms of hypersensitivity reactions and instruct patients or caregivers to seek immediate medical attention if symptoms occur
QTc Interval Prolongation
Advise patients that MODEYSO can cause QTc interval prolongation. Inform patients of the signs and symptoms of QTc prolongation and instruct patients or caregivers to seek immediate medical attention if symptoms occur
Drug Interactions
Inform patients that MODEYSO may interact with some drugs. Advise patients to inform their healthcare provider about all medications they are taking, including prescription and over-the-counter drugs, vitamins, and herbal products. Additionally, patients should consult their healthcare provider before starting or stopping any prescription drug, nonprescription drug, or supplement
Administration
Instruct patients and caregivers to read the
Patients should take MODEYSO orally once weekly on an empty stomach (no food intake at least 1 hour prior to or 3 hours after taking MODEYSO). Take the prescribed dose at the same time on the same day of the week
Instruct patients to swallow capsules whole. For patients unable to swallow capsules whole, instruct patients to open capsules and mix contents with approximately 15 to 30 mL of liquid (sports drink, apple juice, lemonade, or water). Instruct patients to drink the mixture. After drinking the mixture, instruct patients to add another 15 to 30 mL of the liquid to the container, swirl to dissolve any remaining medication, and then drink the remaining contents
Embryo-fetal Toxicity
Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females to inform their healthcare provider of a known or suspected pregnancy
Advise females of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose
Lactation
Advise women not to breastfeed during treatment with MODEYSO and for 1 week after the last dose
Distributed by:
Jazz Pharmaceuticals, Inc.
Palo Alto, CA 94306
9Patient Package Insert
This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 08/2025
10Instructions for Use
This Instructions for Use has been approved by the U.S. Food and Drug Administration. Issued: 08/2025
11PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
RX ONLY
MODEYSO™
125 mg
FOR ORAL USE
See Full Prescribing Information
12PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
