Tovorafenib

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).

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 )

None . None. ( 4 )

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) ].

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) ] .

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.

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) ].

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

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.

12.2 Pharmacodynamics Exposure Response Relationships Tovorafenib exposure is associated with reduction in height-for-age z-scores in pediatric patients. Reduced height-for-age risk persists during treatment with tovorafenib. Higher tovorafenib exposure is associated with increased risk of skin rash, elevated liver enzymes (AST and ALT), and elevated creatine phosphokinase. The exposure-response relationship for overall response rate based on RAPNO-LGG (Response Assessment in Pediatric Neuro-Oncology), and RANO-LGG (Response Assessment in Neuro-Oncology) were not clinically significant over the dosage range of 290 to 476 mg/m 2 (0.76-1.25 times the approved recommended dosage) [see Dosage and Administration (2.3) and Clinical Studies (14) ] . Cardiac Electrophysiology At the recommended OJEMDA dosage of 380 mg/m 2 orally once weekly (not to exceed 600 mg), a mean increase in the QT interval >20 milliseconds was not observed.

12.3 Pharmacokinetics Tovorafenib pharmacokinetic parameters are presented as mean (CV%) unless otherwise indicated. Tovorafenib steady state maximum concentration (C max ) is 6.9 µg/mL (23%) and the area under the concentration-time curve (AUC) is 508 µg*h/mL (31%). Time to reach steady state of tovorafenib is 12 days (33%). Tovorafenib exposure increases in a dose-proportional manner. No clinically significant tovorafenib accumulation occurs. Absorption Tovorafenib median (minimum, maximum) time to achieve peak plasma concentration (T max ) is 3 hours (1.5, 4 hours), following a single dose with tablets or oral suspension. Effect of Food No clinically significant differences in tovorafenib C max and AUC were observed following administration of tablets with a high-fat meal (approximately 859 total calories, 54% fat) compared to fasted conditions, but the T max was delayed to 6.5 hours. Distribution Tovorafenib apparent volume of distribution is 60 L/m 2 (23%). Tovorafenib is 97.5% bound to human plasma proteins in vitro. Elimination Tovorafenib terminal half-life is approximately 56 hours (33%) and the apparent clearance is 0.7 L/h/m 2 (31%). Metabolism Tovorafenib is primarily metabolized by aldehyde oxidase and CYP2C8 in vitro. CYP3A, CYP2C9, and CYP2C19 metabolize tovorafenib to a minor extent. Excretion Following a single oral dose of radiolabeled tovorafenib, 65% of the total radiolabeled dose was recovered in the feces (8.6% unchanged) and 27% of the dose was recovered in the urine (0.2% unchanged). Specific Populations No clinically significant differences of tovorafenib were observed based on age (range: 1 to 94 years), sex, race (White, Black, Asian), mild hepatic impairment [bilirubin ≤ upper limit of normal (ULN) and AST > ULN or bilirubin > 1 to 1.5× ULN and any AST], and mild-to-moderate renal impairment (eGFR) ≥ 30 mL/min/1.73 m 2 calculated by Schwartz equation or MDRD equation. Drug Interaction Studies Clinical Studies and Model-Informed Approaches CYP3A Substrates: Midazolam (CYP3A4 substrate) steady-state C max and AUC are predicted to decrease by at least 20% following coadministration with tovorafenib. In Vitro Studies CYP450 Enzymes : Tovorafenib inhibits CYP2C8, CYP2C9, CYP2C19 and CYP3A, but does not inhibit CYP1A2, CYP2B6, and CYP2D6 at clinically relevant concentrations. Tovorafenib induces CYP3A, CYP2C8, CYP1A2, CYP2B6, CYP2C9 and CYP2C19 at clinically relevant concentrations. Transporter Systems: Tovorafenib is not a substrate of BCRP, P-glycoprotein (P-gp), OATP1B1 and OATP1B3. Tovorafenib has not been evaluated as a substrate of OAT1, OAT3, MATE1, MATE2-K and OCT2. Tovorafenib inhibits BCRP at clinically relevant concentrations.

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.

Exposure Response Relationships Tovorafenib exposure is associated with reduction in height-for-age z-scores in pediatric patients. Reduced height-for-age risk persists during treatment with tovorafenib. Higher tovorafenib exposure is associated with increased risk of skin rash, elevated liver enzymes (AST and ALT), and elevated creatine phosphokinase. The exposure-response relationship for overall response rate based on RAPNO-LGG (Response Assessment in Pediatric Neuro-Oncology), and RANO-LGG (Response Assessment in Neuro-Oncology) were not clinically significant over the dosage range of 290 to 476 mg/m 2 (0.76-1.25 times the approved recommended dosage) [see Dosage and Administration (2.3) and Clinical Studies (14) ] . Cardiac Electrophysiology At the recommended OJEMDA dosage of 380 mg/m 2 orally once weekly (not to exceed 600 mg), a mean increase in the QT interval >20 milliseconds was not observed.

Tovorafenib pharmacokinetic parameters are presented as mean (CV%) unless otherwise indicated. Tovorafenib steady state maximum concentration (C max ) is 6.9 µg/mL (23%) and the area under the concentration-time curve (AUC) is 508 µg*h/mL (31%). Time to reach steady state of tovorafenib is 12 days (33%). Tovorafenib exposure increases in a dose-proportional manner. No clinically significant tovorafenib accumulation occurs. Absorption Tovorafenib median (minimum, maximum) time to achieve peak plasma concentration (T max ) is 3 hours (1.5, 4 hours), following a single dose with tablets or oral suspension. Effect of Food No clinically significant differences in tovorafenib C max and AUC were observed following administration of tablets with a high-fat meal (approximately 859 total calories, 54% fat) compared to fasted conditions, but the T max was delayed to 6.5 hours. Distribution Tovorafenib apparent volume of distribution is 60 L/m 2 (23%). Tovorafenib is 97.5% bound to human plasma proteins in vitro. Elimination Tovorafenib terminal half-life is approximately 56 hours (33%) and the apparent clearance is 0.7 L/h/m 2 (31%). Metabolism Tovorafenib is primarily metabolized by aldehyde oxidase and CYP2C8 in vitro. CYP3A, CYP2C9, and CYP2C19 metabolize tovorafenib to a minor extent. Excretion Following a single oral dose of radiolabeled tovorafenib, 65% of the total radiolabeled dose was recovered in the feces (8.6% unchanged) and 27% of the dose was recovered in the urine (0.2% unchanged). Specific Populations No clinically significant differences of tovorafenib were observed based on age (range: 1 to 94 years), sex, race (White, Black, Asian), mild hepatic impairment [bilirubin ≤ upper limit of normal (ULN) and AST > ULN or bilirubin > 1 to 1.5× ULN and any AST], and mild-to-moderate renal impairment (eGFR) ≥ 30 mL/min/1.73 m 2 calculated by Schwartz equation or MDRD equation. Drug Interaction Studies Clinical Studies and Model-Informed Approaches CYP3A Substrates: Midazolam (CYP3A4 substrate) steady-state C max and AUC are predicted to decrease by at least 20% following coadministration with tovorafenib. In Vitro Studies CYP450 Enzymes : Tovorafenib inhibits CYP2C8, CYP2C9, CYP2C19 and CYP3A, but does not inhibit CYP1A2, CYP2B6, and CYP2D6 at clinically relevant concentrations. Tovorafenib induces CYP3A, CYP2C8, CYP1A2, CYP2B6, CYP2C9 and CYP2C19 at clinically relevant concentrations. Transporter Systems: Tovorafenib is not a substrate of BCRP, P-glycoprotein (P-gp), OATP1B1 and OATP1B3. Tovorafenib has not been evaluated as a substrate of OAT1, OAT3, MATE1, MATE2-K and OCT2. Tovorafenib inhibits BCRP at clinically relevant concentrations.

, Mutagenesis, Impairment of Fertility Tovorafenib was not carcinogenic in the 6-month study in transgenic rasH2 mice that received oral doses up to 100 mg/kg/day. Tovorafenib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay. Tovorafenib was not genotoxic in cultured human lymphocytes without metabolic activation. Tovorafenib induced chromosomal aberrations in cultured human lymphocytes with metabolic activation at a single concentration in vitro. Tovorafenib was not genotoxic in an in vivo rat bone marrow micronucleus assay. In a fertility and early embryonic development study in rats, animals were administered tovorafenib doses of 37.5, 75, or 150 mg/kg/day orally. Female animals, paired with untreated males, were dosed for 14 days prior to pairing, during the mating period, and up to Gestation Day 6. Tovorafenib decreased the number of pregnancies, corpora lutea, and live embryos, as well as increased post-implantation losses 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. In repeat- dose toxicology studies in rats of up to 3 months duration, tovorafenib-related findings in female rats included reversible increased thickness of the vaginal mucosa, increased size and/or numbers of corpora hemorrhagicum and hemorrhage, and non-reversible cystic follicles, decreased corpora lutea, and interstitial cell hyperplasia were observed in ovaries at doses ≥ 50 mg/kg once every other day (approximately 0.4-fold the human exposure at the recommended dose based on AUC). In male rats, tovorafenib reduced weights of epididymis and testes, which correlated with reversible tubular degeneration/atrophy of the testes and reduced epididymal sperm at doses ≥ 50 mg/kg once every other day (approximately 0.3-fold the human exposure at the recommended dose based on AUC).

17 PATIENT COUNSELING 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.

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.