Ojemda

tovorafenib · Kit · Oral

Uses

1 INDICATIONS AND USAGE OJEMDA is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. This indication is approved under accelerated approval based on response rate and duration of response [see Clinical Studies (14) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). OJEMDA is a kinase inhibitor indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. ( 1 ) This indication is approved under accelerated approval based on response rate and duration of response [see Clinical Studies (14) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dosage and administration

Confirm the presence of BRAF fusion or rearrangement, or BRAF V600 mutation prior to initiation of treatment with OJEMDA. ( 2.1 ) Recommended dosage of OJEMDA is based on body surface area ( see Tables 1 and 2 ). ( 2.3 ) Administer OJEMDA orally, once weekly, with or without food. ( 2.3 , 2.4 ). Tablets : Swallow tablets whole with water. Do not chew, cut, or crush. ( 2.4 ) For Oral Suspension : See full prescribing information for preparation and administration instructions. ( 2.4 ) 2.1 Patient Selection Select patients for treatment with OJEMDA based on the presence of BRAF fusion or rearrangement, or BRAF V600 mutation in tumor specimens [see Clinical Studies (14) ]. Information on FDA-approved tests for the detection of BRAF fusions, BRAF rearrangements, and BRAF V600 mutations is available at http://www.fda.gov/companiondiagnostics . 2.2 Recommended Testing Before Initiating OJEMDA Before initiating OJEMDA, evaluate liver function tests, including ALT, AST and bilirubin [see Warnings and Precautions (5.3) ]. 2.3 Recommended Dosage The recommended dosage of OJEMDA based on body surface area (BSA) is 380 mg/m 2 orally once weekly (the maximum recommended dosage is 600 mg orally once weekly) with or without food [see Administration (2.4) and Clinical Pharmacology (12.3) ] until disease progression or intolerable toxicity. OJEMDA may be administered as an immediate release tablet (see Table 1 ) or as an oral suspension (see Table 2 ). A recommended dosage for patients with BSA less than 0.3 m 2 has not been established. Table 1 Recommended OJEMDA Tablets Dosage Based on Body Surface Area Body Surface Area (m 2 ) Recommended Dosage 0.30-0.89 Administer OJEMDA oral suspension once weekly (see Table 2 ) 0.90-1.12 400 mg once weekly 1.13-1.39 500 mg once weekly ≥ 1.40 600 mg once weekly Table 2 Recommended Dosage for OJEMDA for Oral Suspension Based on Body Surface Area Body Surface Area (m 2 ) Dose Volume (mL) OJEMDA for oral suspension has a concentration of 25 mg/mL. Each bottle of OJEMDA for oral suspension delivers 300 mg/12 mL. Dosage 0.30-0.35 5 125 mg once weekly 0.36-0.42 6 150 mg once weekly 0.43-0.48 7 175 mg once weekly 0.49-0.54 8 200 mg once weekly 0.55-0.63 9 225 mg once weekly 0.64-0.77 11 275 mg once weekly 0.78-0.83 12 300 mg once weekly 0.84-0.89 14 350 mg once weekly 0.90-1.05 15 375 mg once weekly 1.06-1.25 18 450 mg once weekly 1.26-1.39 21 525 mg once weekly ≥1.40 24 600 mg once weekly Continue once weekly dosing until disease progression or intolerable toxicity. 2.4 Administration Take OJEMDA at a regularly scheduled time once weekly. OJEMDA may be taken with or without food [see Clinical Pharmacology (12.3) ]. If a dose is missed by: 3 days or less, take the missed dose as soon as possible, and take the next dose on its regularly scheduled day. more than 3 days, skip the missed dose and take the next dose on its regularly scheduled day. If vomiting occurs immediately after taking a dose, repeat that dose. OJEMDA tablets Swallow tablets whole with water. Do not chew, cut, or crush. OJEMDA for oral suspension Prior to first time use of OJEMDA for oral suspension, ensure that caregivers (and if appropriate, patients) read and understand the "Instructions for Use" before preparing, measuring, and administering OJEMDA. Preparation and Administration Reconstitute the powder in each supplied bottle with exactly 14 mL of room temperature water to form the OJEMDA for oral suspension. After reconstitution each mL contains 25 mg of tovorafenib. Product foaming after reconstitution reduces the deliverable volume. Each bottle delivers 300 mg of tovorafenib in 12 mL. For doses greater than 300 mg, reconstitute two bottles to achieve the dose. Split the dose as equally as possible between the two bottles (e.g., 6 mL and 7 mL for a 325 mg dose). Prepare the first bottle and administer dose prior to preparing the second bottle. Administer OJEMDA for oral suspension using the supplied oral dosing syringe or feeding tube (minimum 12 French) immediately after preparation. If the OJEMDA for oral suspension is not administered within 15 minutes after preparation, instruct the patient to discard it. 2.5 Dosage Modifications for Adverse Reactions The recommended dosage reductions for adverse reactions for OJEMDA tablets are provided in Table 3 and OJEMDA for oral suspension in Table 4. Table 3 OJEMDA Tablets: Recommended Dosage Reductions for Adverse Reactions BSA (m 2 ) First Dosage Reduction Second Dosage Reduction 0.30-1.12 Administer the oral suspension once weekly (see Table 4 ) 1.13-1.39 400 mg once weekly Administer OJEMDA oral suspension once weekly (see Table 4 ) ≥1.40 500 mg once weekly 400 mg once weekly Table 4 OJEMDA for Oral Suspension: Recommended Dosage Reductions for Adverse Reactions BSA (m 2 ) First Dosage Reduction Second Dosage Reduction Volume (mL) Dose (mg) Volume (mL) Dose (mg) 0.30-0.35 4 100 mg once weekly 3 75 mg once weekly 0.36-0.42 5 125 mg once weekly 4 100 mg once weekly 0.43-0.48 6 150 mg once weekly 5 125 mg once weekly 0.49-0.54 7 175 mg once weekly 6 150 mg once weekly 0.55-0.63 8 200 mg once weekly 6 150 mg once weekly 0.64-0.77 9 225 mg once weekly 8 200 mg once weekly 0.78-0.83 10 250 mg once weekly 8 200 mg once weekly 0.84-0.89 12 300 mg once weekly 10 250 mg once weekly 0.90-1.05 13 325 mg once weekly 11 275 mg once weekly 1.06-1.25 15 375 mg once weekly 13 325 mg once weekly 1.26-1.39 18 450 mg once weekly 15 375 mg once weekly ≥1.40 20 500 mg once weekly 16 400 mg once weekly The recommended dosage modifications of OJEMDA for adverse reactions are in Table 5. Table 5 Recommended Dosage Modifications for Adverse Reactions Severity of ADR National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Dosage Modification See Table 3 and Table 4 for recommended dosage reductions. Hemorrhage [see Warnings and Precautions (5.1) ] Intolerable Grade 2 Any Grade 3 Withhold OJEMDA.

Dosage forms and strengths

Tablets: 100 mg: orange, film-coated, oval tablets debossed with "100"; on one side and "D101" on the opposite side. Each tablet contains 100 mg of tovorafenib. For Oral Suspension: 25 mg/mL: white to off white powder. After reconstitution, each mL of strawberry flavored tovorafenib suspension contains 25 mg of tovorafenib. Each bottle delivers 300 mg of tovorafenib in 12 mL. Tablets: 100 mg ( 3 ) For Oral Suspension: 25 mg/mL ( 3 )

Contraindications

None . None. ( 4 )

Warnings and precautions

Hemorrhage: Major hemorrhagic events can occur during treatment with OJEMDA. Withhold, resume at reduced dose, or permanently discontinue based on severity. ( 5.1 ) Skin Toxicity Including Photosensitivity : Advise patients to monitor for new or worsening skin reactions. Advise patients to limit direct ultraviolet exposure and use precautionary measures such as sunscreen, sunglasses and/or protective clothing during treatment with OJEMDA. Withhold, reduce the dose or permanently discontinue based on severity. ( 5.2 ) Hepatotoxicity: OJEMDA can cause hepatotoxicity. Monitor liver function tests prior to administration and during treatment. Withhold, reduce the dose or permanently discontinue based on severity. ( 5.3 ) Effect on Growth : Reductions in growth velocity have been reported. Routinely monitor growth in pediatric patients. ( 5.4 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise of the potential risk to a fetus and to use effective nonhormonal contraception. ( 5.5 , 8.1 , 8.3 ) NF1 Associated Tumors : Increased tumor growth may occur with OJEMDA. (5.6, 13.2) 5.1 Hemorrhage Hemorrhage, including major hemorrhage defined as symptomatic bleeding in a critical area or organ, can occur with OJEMDA. In the pooled safety population [see Adverse Reactions (6.1) ], hemorrhagic events occurred in 37% of patients, including epistaxis in 26% and intratumoral hemorrhage in 9%. Serious events of bleeding occurred in 5% of patients including Grade 5 tumor hemorrhage in 1 patient (0.6%). OJEMDA was permanently discontinued for hemorrhage in 2% of patients. Advise patients and caregivers of the risk of hemorrhage during treatment with OJEMDA. Monitor for signs and symptoms of hemorrhage and evaluate as clinically indicated . Withhold and resume at reduced dose upon improvement, or permanently discontinue based on severity [see Dosage and Administration (2.5) ]. 5.2 Skin Toxicity Including Photosensitivity OJEMDA can cause rash, including maculopapular rash and photosensitivity. In the pooled safety population [see Adverse Reactions (6.1) ], rash occurred in 67% of patients treated with OJEMDA, including Grade 3 rash in 12%. Rash resulted in dose interruption in 15% of patients and dose reduction in 7% of patients. OJEMDA was permanently discontinued due to rash in 1% of patients (n=2). In the pooled safety population, dermatitis acneiform occurred in 26% of patients treated with OJEMDA, including Grade 3 dermatitis acneiform in 0.6% of patients (n=1). Dose reduction was required in 2% of patients (n=3) due to dermatitis acneiform. Monitor for new or worsening skin reactions. Consider dermatologic consultation and initiate supportive care as clinically indicated. Withhold, reduce the dose, or permanently discontinue OJEMDA based on severity of adverse reaction [see Dosage and Administration (2.5) ]. Photosensitivity In the pooled safety population [see Adverse Reactions (6.1) ], photosensitivity occurred in 12% of patients treated with OJEMDA, including Grade 3 events in 0.6% of patients (n=1). Advise patients to use precautionary measures against ultraviolet exposure such as use of sunscreen, sunglasses, and/or protective clothing during treatment with OJEMDA. Withhold, reduce the dose, or permanently discontinue OJEMDA based on severity of adverse reaction [see Dosage and Administration (2.5) ]. 5.3 Hepatotoxicity OJEMDA can cause hepatotoxicity. In the pooled safety population [see Adverse Reactions (6.1) ] , increased alanine aminotransferase (ALT) occurred in 42% and increased aspartate aminotransferase (AST) occurred in 74%, including Grade 3 ALT in 4% and increased AST in 2% of patients treated with OJEMDA. The median time to onset of increased ALT or AST was 14 days (range: 3 to 280 days). Increased ALT or AST leading to dose interruption occurred in 5% of patients and dose reductions were required in 1.2% of patients. Increased bilirubin occurred in 23% of patients, including Grade 3 increased bilirubin in 0.6% of patients (n=1) treated with OJEMDA. Hyperbilirubinemia leading to dose discontinuation occurred in a single adult patient with an advanced non-CNS solid tumor. Monitor liver function tests, including ALT, AST and bilirubin, before initiation of OJEMDA, one month after initiation and then every three months thereafter and as clinically indicated. Withhold and resume at the same or reduced dose upon improvement, or permanently discontinue OJEMDA based on the severity [see Dosage and Administration (2.5) ]. 5.4 Effect on Growth OJEMDA can cause reductions in growth velocity. In FIREFLY-1 [see Adverse Reactions (6.1) ] , treatment-emergent adverse effects on growth were reported in 46% of 133 patients 18 years of age or younger; 35% were Grade 3 or higher. Reduction in growth velocity resulted in dose interruption in 5% of patients, dose reduction in 2.3% of patients, and permanent discontinuation in 3% of patients. The median change from baseline in height percentile was -14 (z-score change -0.6) for evaluable patients on study for 12 months (N=107) and -20 (z-score change -0.9) for evaluable patients on study for 18 months (N=95). Growth velocity improved after interruption of treatment with OJEMDA. Among 81 evaluable patients, the median annualized growth velocity ranged from 0.86 to 1.8 cm/year during the 2-year treatment period. Of those, 17 patients had height measurements recorded at least 90 days off-treatment and had a 4.2 cm/year median annualized growth velocity. Routinely monitor patient growth during treatment with OJEMDA [see Adverse Reactions (6) , Use in Specific Populations (8.4) ]. 5.5 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, OJEMDA may cause fetal harm when administered to a pregnant woman. Tovorafenib was embryo lethal in rats at doses approximately 0.8-fold the human exposure at the recommended dose based on area under the curve (AUC).

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Hemorrhage [see Warnings and Precautions (5.1) ] Skin Toxicity Including Photosensitivity [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.3) ] Effect on Growth [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥30%) were rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased phosphate, decreased hemoglobin, increased creatine phosphokinase, increased alanine aminotransferase, decreased albumin, decreased lymphocytes, decreased leukocytes, increased aspartate aminotransferase, decreased potassium, and decreased sodium. To report SUSPECTED ADVERSE REACTIONS, contact Day One Biopharmaceuticals at toll-free phone # 1-877-204-2820 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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 safety population described in WARNINGS AND PRECAUTIONS reflects exposure to OJEMDA taken orally once weekly at a dose based on body surface area [see Clinical Studies (14) ] in 140 patients with relapsed or refractory pediatric LGG or advanced solid tumors harboring a RAF alteration and a flat dose of 600 mg in 32 adult patients with advanced solid tumors until disease progression or intolerable toxicity. Among 172 patients treated with OJEMDA, 86% were exposed for 6 months or longer and 49% were exposed for 1 year or longer. Pediatric Low-grade Glioma The safety of OJEMDA was evaluated in 137 patients with relapsed or refractory pediatric LGG harboring a BRAF alteration in FIREFLY-1 (Arms 1 and 2) [see Clinical Studies (14) ]. Patients received OJEMDA at a dose based on body surface area [see Dosage and Administration (2.3 ] orally once weekly until disease progression or intolerable toxicity. The median age of patients was 9 years (range 1 to 24 years); 53% male; 58% White, 7% Asian, 2% Black or African American, 6% other races, 25% race was not reported; 2.9% were Hispanic or Latino; and 90% Karnofsky/Lansky performance status of 80 to 100. Serious adverse reactions occurred in 45% of patients who received OJEMDA. Serious adverse reactions in >2% of patients included viral infection (9%), pneumonia (4%), and sepsis (4%). A fatal adverse reaction of tumor hemorrhage occurred in 1 patient (1%). Permanent discontinuation of OJEMDA due to an adverse reaction occurred in 7% of patients. Adverse reactions which resulted in permanent discontinuation of OJEMDA in more than one patient were tumor hemorrhage and reduction in growth velocity. Dosage interruptions of OJEMDA due to an adverse reaction occurred in 57% of patients. Adverse reactions which required dose interruption in ≥5% of patients included rash, pyrexia, vomiting, and hemorrhage. Dosage reductions of OJEMDA due to an adverse reaction occurred in 24% of patients. Adverse reactions which required dose reduction in ≥2% of patients included rash, and fatigue. The most common adverse reactions (≥30%) were rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased phosphate, decreased hemoglobin, increased creatine phosphokinase, increased alanine aminotransferase, decreased albumin, decreased lymphocytes, decreased leukocytes, increased aspartate transferase, decreased potassium, and decreased sodium. Table 6 and Table 7 present adverse reactions and laboratory abnormalities, respectively, identified in FIREFLY-1 (Arms 1 and 2). Table 6 Adverse Reactions (≥20%) in Patients with Pediatric LGG Who Received OJEMDA in FIREFLY-1 (Arms 1 and 2) Adverse Reaction OJEMDA (N=137) All Grades (%) Grade 3 or 4 (%) Skin and Subcutaneous Tissue Disorders Rash Includes terms erythema multiforme, eczema, rash erythematous, rash macular, rash follicular, rash pruritic, rash maculopapular, rash, rash papular, rash pustular, skin exfoliation, drug eruption, dermatitis, dermatitis bullous. 77 12 Hair color changes 76 0 Dry skin 36 0 Dermatitis acneiform 31 1 Pruritus 26 1 General Disorders Fatigue 55 4 Pyrexia 39 4 Edema Includes terms lip edema, periorbital edema, edema peripheral, localized edema, face edema, vulval edema. 26 0 Infections and Infestations Viral infection Includes terms viral infection, rhinovirus infection, enterovirus infection, viral upper respiratory tract infection, enterocolitis viral, oral herpes, gastroenteritis viral, influenza, influenza like illness, respiratory syncytial virus infection, enterovirus infection, coronavirus infection, COVID-19, SARS-COV-2 test positive, herpes simplex, parainfluenza virus infection, adenoviral upper respiratory infection, viraemia, adenovirus infection, conjunctivitis viral, eye infection viral, metapneumovirus infection, parvovirus infection, respiratory syncytial virus bronchiolitis, respiratory tract infection viral, viral pharyngitis, viral rhinitis, viral tonsillitis. 55 7 Upper respiratory tract infection 31 1.5 Paronychia 26 1.5 Gastrointestinal Disorders Vomiting Includes terms retching, hematemesis. 50 4 Constipation 33 0 Nausea 33 0 Abdominal pain 28 0 Diarrhea Includes terms colitis, enterocolitis. 22 1.5 Stomatitis Includes terms mouth ulceration, mucosal inflammation, aphthous ulcer, cheilitis.

Drug interactions

Moderate and Strong CYP2C8 Inhibitors : Avoid coadministration with OJEMDA. ( 7.1 ). Moderate and Strong CYP2C8 Inducers : Avoid coadministration with OJEMDA. ( 7.1 ). Certain CYP3A Substrates : Avoid coadministration of OJEMDA with CYP3A substrates where minimal concentration changes can cause reduced efficacy. ( 7.2 ). Hormonal contraceptives : Avoid coadministration with OJEMDA. ( 7.2 ). 7.1 Effects of Other Drugs on OJEMDA Table 8 describes drug interactions where coadministration with another drug affects OJEMDA. Table 8 Coadministration with Other Drugs that Affect the Use of OJEMDA Strong or Moderate CYP2C8 Inhibitors Prevention or Management Avoid coadministration of OJEMDA with a strong or moderate CYP2C8 inhibitor. Mechanism and Clinical Effect(s) Tovorafenib is a CYP2C8 substrate. Strong or moderate CYP2C8 inhibitors are predicted to increase tovorafenib exposure based on a mechanistic understanding of its elimination [see Clinical Pharmacology (12.3) ], which may increase the risk of adverse reactions with OJEMDA. Strong or Moderate CYP2C8 Inducers Prevention or Management Avoid coadministration of OJEMDA with a strong or moderate CYP2C8 inducer. Mechanism and Clinical Effect(s) Tovorafenib is a CYP2C8 substrate. Strong or moderate CYP2C8 inducers are predicted to decrease tovorafenib exposure based on a mechanistic understanding of its elimination [see Clinical Pharmacology (12.3) ], which may reduce the effectiveness of OJEMDA. 7.2 Effects of OJEMDA on Other Drugs Table 9 describes drug interactions where coadministration with OJEMDA affects another drug. Table 9 Coadministration with OJEMDA that Affects the Use of Other Drugs CYP3A Substrates Prevention or Management Hormonal Contraceptives : Avoid coadministration of hormonal contraceptives with OJEMDA. If coadministration is unavoidable, use an additional effective nonhormonal contraceptive method during coadministration and for 28 days after discontinuation of OJEMDA. Other CYP3A Substrates: Avoid coadministration of OJEMDA with certain CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures. If coadministration is unavoidable, monitor patients for loss of efficacy unless otherwise recommended in the Prescribing Information for CYP3A substrates. Mechanism and Clinical Effect(s) Tovorafenib is a CYP3A inducer. Tovorafenib is predicted to decrease exposure of certain CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures [see Clinical Pharmacology (12.3) ], which may reduce the effectiveness of these substrates. Coadministration with hormonal contraceptives (CYP3A substrate) may decrease progestin-x and ethinyl estradiol exposure, which may lead to contraceptive failure and/or an increase in breakthrough bleeding [see Warnings and Precautions (5.5) , Use in Specific Populations (8.3) ].

Use in specific populations

Lactation : Advise not to breastfeed. ( 8.2 ) Infertility : May impair fertility in males and females. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ], OJEMDA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of OJEMDA in pregnant women. Oral administration of tovorafenib to pregnant rats during the period of organogenesis resulted in embryo lethality at exposures 0.8 times the human exposure at the recommended dose based on AUC ( see Data ). Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, once daily oral administration of tovorafenib to pregnant rats during the period of organogenesis from gestation days 7 through 17 at doses of 37.5, 75, and 150 mg/kg resulted in early resorptions and total litter loss at all doses. The dose of 37.5 mg/kg/day is approximately 0.8-fold the human exposure at the recommended dose based on AUC. 8.2 Lactation Risk Summary There are no data on the presence of tovorafenib or its metabolites in human milk, their effects on the breastfed child, or on milk production. Due to the potential for serious adverse reactions in breastfed children from OJEMDA, advise lactating women not to breastfeed during treatment with OJEMDA and for 2 weeks following the last dose. 8.3 Females and Males of Reproductive Potential OJEMDA can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ]. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating OJEMDA [see Use in Specific Populations (8.1) ] . Contraception Females Advise females of reproductive potential to use effective nonhormonal contraception during treatment with OJEMDA and for 28 days after the last dose. OJEMDA can render hormonal contraceptives ineffective [see Drug Interactions (7.2) ]. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with OJEMDA and for 2 weeks after the last dose. Infertility Based on findings in animals, OJEMDA may impact fertility in males and females of reproductive potential. The effects on male animal fertility were reversible. The effects on female animal fertility were not reversible [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use The safety and effectiveness of OJEMDA in pediatric patients 6 months of age and older with relapsed or refractory pediatric LGG harboring a BRAF fusion or rearrangement, or BRAF V600 mutation have been established based on data from a multicenter, open-label, single-arm clinical trial [see Clinical Studies (14) ] . The efficacy of OJEMDA was evaluated in 76 patients with relapsed or refractory pediatric LGG . The safety of OJEMDA was evaluated in 137 patients with relapsed or refractory pediatric LGG in FIREFLY-1 (Arms 1 and 2). Of these 137 patients, 2% (n=3) were 6 month to < 2 years of age, 67% (n=92) were 2 years to < 12 years of age, and 31% (n=42) were >12 years of age [see Adverse Reactions (6.1) ]. C max and AUC in pediatric patients aged 11 months to 17 years were within the range of values observed in adults given the same dose per body surface area. The safety and effectiveness of OJEMDA in patients younger than 6 months of age have not been established. Effect on Growth Patients with pediatric LGG treated with OJEMDA for up to 24 months showed reductions from baseline in Z-scores for height compared to age and sex-matched normative data. Among 35 patients who experienced reductions in growth velocity who had hand radiographs taken to assess bone age, there was no evidence of premature closure of the epiphyseal growth plates or advancement of bone age. Patients followed after interruption of treatment with OJEMDA showed recovery of growth and increase in Z-scores. Monitor growth routinely during treatment [see Warnings and Precautions (5.4) ]. 8.6 Hepatic Impairment No dose adjustment is recommended for patients with mild (bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or bilirubin > 1× to 1.5× ULN and any AST) hepatic impairment. OJEMDA has not been studied in patients with moderate (bilirubin > 1.5× to 3× ULN and any AST) to severe (bilirubin > 3× ULN and any AST) hepatic impairment [see Clinical Pharmacology (12.3) ]. 8.7 Renal Impairment No dose adjustment is recommended for patients with mild-to-moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m 2 calculated by Schwartz equation or MDRD equation). OJEMDA has not been studied in patients with severe renal impairment (eGFR <30 mL/min/1.73 m 2 ) [see Clinical Pharmacology (12.3) ] .

Pregnancy

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ], OJEMDA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of OJEMDA in pregnant women. Oral administration of tovorafenib to pregnant rats during the period of organogenesis resulted in embryo lethality at exposures 0.8 times the human exposure at the recommended dose based on AUC ( see Data ). Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, once daily oral administration of tovorafenib to pregnant rats during the period of organogenesis from gestation days 7 through 17 at doses of 37.5, 75, and 150 mg/kg resulted in early resorptions and total litter loss at all doses. The dose of 37.5 mg/kg/day is approximately 0.8-fold the human exposure at the recommended dose based on AUC.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of OJEMDA in pediatric patients 6 months of age and older with relapsed or refractory pediatric LGG harboring a BRAF fusion or rearrangement, or BRAF V600 mutation have been established based on data from a multicenter, open-label, single-arm clinical trial [see Clinical Studies (14) ] . The efficacy of OJEMDA was evaluated in 76 patients with relapsed or refractory pediatric LGG . The safety of OJEMDA was evaluated in 137 patients with relapsed or refractory pediatric LGG in FIREFLY-1 (Arms 1 and 2). Of these 137 patients, 2% (n=3) were 6 month to < 2 years of age, 67% (n=92) were 2 years to < 12 years of age, and 31% (n=42) were >12 years of age [see Adverse Reactions (6.1) ]. C max and AUC in pediatric patients aged 11 months to 17 years were within the range of values observed in adults given the same dose per body surface area. The safety and effectiveness of OJEMDA in patients younger than 6 months of age have not been established. Effect on Growth Patients with pediatric LGG treated with OJEMDA for up to 24 months showed reductions from baseline in Z-scores for height compared to age and sex-matched normative data. Among 35 patients who experienced reductions in growth velocity who had hand radiographs taken to assess bone age, there was no evidence of premature closure of the epiphyseal growth plates or advancement of bone age. Patients followed after interruption of treatment with OJEMDA showed recovery of growth and increase in Z-scores. Monitor growth routinely during treatment [see Warnings and Precautions (5.4) ].

Description

11 DESCRIPTION OJEMDA contains tovorafenib, a kinase inhibitor. Tovorafenib has the molecular formula C 17 H 12 Cl 2 F 3 N 7 O 2 S and a molecular weight of 506.29. The chemical name for tovorafenib is 6-amino-5-chloro-N-[(1R)-1-[5-[[[5-chloro-4-(trifluoromethyl)-2-pyridinyl]amino]carbonyl]-2-thiazolyl]ethyl]-4-pyrimidinecarboxamide. Tovorafenib has the following chemical structure: It is a white to off-white powder. The solubility of tovorafenib at 37ºC is ≤ 3 micrograms/mL from pH 1.2 to 8 in aqueous media. OJEMDA (tovorafenib) tablets are supplied as 100 mg strength tablets for oral administration. Each tablet contains 100 mg tovorafenib and the following inactive ingredients: copovidone, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and orange film coating (hypromellose, polyethylene glycol 8000, titanium dioxide, ferric oxide yellow, ferric oxide red). OJEMDA (tovorafenib) for oral suspension is a white to off white powder which produces a white suspension when reconstituted with water. Each mL of reconstituted tovorafenib suspension contains 25 mg of tovorafenib and the following inactive ingredients: artificial strawberry flavor, colloidal silicon dioxide, copovidone, maltodextrin, mannitol, microcrystalline cellulose, simethicone, sodium lauryl sulfate, and sucralose. Chemical Structure

Mechanism of action

12.1 Mechanism of Action Tovorafenib is a Type II RAF kinase inhibitor of mutant BRAF V600E , wild-type BRAF , and wild-type CRAF kinases. Tovorafenib exhibited antitumor activity in cultured cells and xenograft tumor models harboring BRAF V600E and V600D mutations, and in a xenograft model harboring a BRAF fusion.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING OJEMDA tablets: 100 mg: orange, film-coated, oval tablets debossed with "100" on one side and "D101" on the opposite side and supplied as follows: Weekly dose Each carton contains Each blister card contains NDC 400 mg 4 blister cards four 100 mg tablets NDC 82950-001-16 500 mg 4 blister cards five 100 mg tablets NDC 82950-001-20 600 mg 4 blister cards six 100 mg tablets NDC 82950-001-24 Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense product in the original package. Tablets should not be removed from blister cards until immediately before use. OJEMDA for oral suspension: 25 mg/mL: white to off white powder in a clear glass bottle, co-packaged with a press-in bottle adaptor and a 20 mL oral dosing syringe (NDC# 82950-012-01). Each mL of reconstituted, strawberry flavored tovorafenib suspension contains 25 mg of tovorafenib. Each bottle delivers 300 mg of tovorafenib in 12 mL. Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not use if safety seal under cap is broken or missing. Suspension must be used immediately after reconstitution. Discard the bottle (including any unused portion) and syringe after dosing.

Storage

OJEMDA for oral suspension: 25 mg/mL: white to off white powder in a clear glass bottle, co-packaged with a press-in bottle adaptor and a 20 mL oral dosing syringe (NDC# 82950-012-01). Each mL of reconstituted, strawberry flavored tovorafenib suspension contains 25 mg of tovorafenib. Each bottle delivers 300 mg of tovorafenib in 12 mL. Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not use if safety seal under cap is broken or missing. Suspension must be used immediately after reconstitution. Discard the bottle (including any unused portion) and syringe after dosing.

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Hemorrhage Advise patients that OJEMDA can cause bleeding and to contact their healthcare provider for signs or symptoms of bleeding [see Warnings and Precautions (5.1) ]. Skin Toxicities Advise patients that OJEMDA can cause skin toxicities and to contact their healthcare provider for worsening or intolerable rash [see Warnings and Precautions (5.2) ]. Photosensitivity Advise patients that OJEMDA can cause photosensitivity. Advise patients to limit direct ultraviolet exposure during treatment with OJEMDA. Recommend that patients use precautionary measures such as use of sunscreen, sunglasses, and/or protective clothing during treatment with OJEMDA [see Warnings and Precautions (5.2) ]. Hepatotoxicity Advise patients that OJEMDA can cause liver toxicity and to contact their healthcare provider for signs or symptoms of liver dysfunction. Advise patients that serial testing of serum liver tests (ALT, AST, bilirubin) is recommended during treatment with OJEMDA [see Warnings and Precautions (5.3) ] . Effect on Growth Advise patients and caregivers that treatment with OJEMDA may cause a reduction in growth velocity, and that growth will be monitored during treatment with OJEMDA [see Warnings and Precautions (5.4) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus [see Warnings and Precautions (5.5) , Use in Specific Populations (8.1 , 8.3) ]. Advise females to inform their healthcare provider of a known or suspected pregnancy during treatment with OJEMDA. Advise females of reproductive potential to use effective nonhormonal contraception during treatment and for 28 days after discontinuation of treatment with OJEMDA. Advise male patients with female partners of reproductive potential to use effective nonhormonal contraception during treatment with OJEMDA and for 2 weeks after the last dose. Lactation Advise women not to breastfeed during treatment with OJEMDA and for 2 weeks after the last dose of OJEMDA [see Use in Specific Populations (8.2) ] . Infertility Advise males and females of reproductive potential of the potential risk for impaired fertility with OJEMDA [see Nonclinical Toxicology (13.1) ] . Dosing and Administration Inform patients and caregivers on how to take OJEMDA and what to do for missed or vomited doses [see Dosage and Administration (2.4) ]. Prior to use of the oral suspension, ensure patients or caregivers receive training on proper dosing, preparation, and administration [see Dosage and Administration (2.4) and Instructions for Use ]. Storage Advise patients not to take the OJEMDA tablets out of the blister card until ready to use. Discard the bottle (including any unused portion) and syringe after dosing. OJEMDA is a trademark of Day One Biopharmaceuticals Inc. © 2025 Day One Biopharmaceuticals, Inc. All rights reserved.

Label text from the FDA structured product label by Day One Biopharmaceuticals, Inc. (revised Sep 2, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Tovorafenib in 1 product

Ojemda NDC products (2)

NDC	Strength & form	Labeler	Type
82950-001	Tovorafenib 100 mg/1 Tablet, Film Coated	Day One Biopharmaceuticals, Inc.	NDA
82950-012	Kit	Day One Biopharmaceuticals, Inc.	NDA

Frequently asked questions

What is Ojemda used for?

What are the side effects of Ojemda?

Who makes Ojemda?

Ojemda is listed by 1 labeler in the FDA NDC directory, including Day One Biopharmaceuticals, Inc..