Ojemda

Description for Ojemda

OJEMDA contains tovorafenib, a kinase inhibitor. Tovorafenib has the molecular formula C₁₇H₁₂Cl₂F₃N₇O₂S and a molecular weight of 506.29. The chemical name for tovorafenib is 6-amino-5-chloro-N-[(1R)-1-[5-[[[5chloro-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 37°C 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 Opadry® Orange.

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.

ADVERSE REACTIONS

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)]

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
Rasha	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
Edemab	26	0
Infections and Infestations
Viral infectionc	55	7
Upper respiratory tract infection	31	1.5
Paronychia	26	1.5
Gastrointestinal Disorders
Vomitingd	50	4
Constipation	33	0
Nausea	33	0
Abdominal pain	28	0
Diarrheae	22	1.5
Stomatitisf	20	0
Nervous system disorders
Headache	45	1
Vascular Disorders
Hemorrhageg	42	5*
a 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. b Includes terms lip edema, periorbital edema, edema peripheral, localized edema, face edema, vulval edema. c 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. d Includes terms retching, hematemesis. e Includes terms colitis, enterocolitis. f Includes terms mouth ulceration, mucosal inflammation, aphthous ulcer, cheilitis. g Includes terms tumor hemorrhage, gastrointestinal hemorrhage, subdural hemorrhage, epistaxis, intracranial tumor hemorrhage, upper gastrointestinal hemorrhage, lower gastrointestinal hemorrhage, vaginal hemorrhage, gingival bleeding, post procedural hemorrhage, hemoptysis, anal hemorrhage. * Includes one Grade 5 event.

Other clinically important adverse reactions observed in <20% of patients treated with OJEMDA were reductions in growth velocity [see Warnings and Precautions (5.4)] skin discoloration, myalgia, photosensitivity reaction [see Warnings and Precautions (5.2)], and arthralgia.

Table 7 Select Laboratory Abnormalities (≥20%) that Worsened from Baseline in Patients with Pediatric LGG Who Received OJEMDA in FIREFLY-1 (Arms 1 and 2)

Laboratory Abnormality1	OJEMDA2
	All Grades (%)	Grade 3 or 4 (%)
Hematology
Decreased hemoglobin	90	15
Decreased lymphocytes	50	2
Decreased leukocytes	31	2
Increased lymphocytes	23	0
Chemistry
Decreased phosphate	87	25
Increased AST	83	2
Increased creatine phosphokinase	83	11
Increased LDH	73	0
Decreased potassium	51	2
Increased ALT	50	5
Increased bilirubin	22	1
Decreased albumin	24	5
Decreased sodium	20	2
1 Severity as defined by National Cancer Institute CTCAE v5.0 2 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 67 to 137 patients.

Increased creatine phosphokinase was a clinically important laboratory abnormality that worsened from baseline in patients treated with OJEMDA.

Drug Interactions for Ojemda

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.

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 andClinical 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)].

Warnings for Ojemda

Included as part of the PRECAUTIONS section.

Precautions for Ojemda

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)].

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)].

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)].

Effect on Growth

OJEMDA can cause reductions in growth velocity. In FIREFLY-1 [see Adverse Reactions (6.1)], treatmentemergent 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)].

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). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with OJEMDA and for 28 days after the last dose, since OJEMDA can render some hormonal contraceptives ineffective [see Drug Interactions (7.2)]. 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 [see Use in Specific Populations (8.1, 8.3)].

NF1 Associated Tumors

Based on nonclinical data in NF1 models without BRAF alterations, tovorafenib may promote tumor growth in patients with NF1 tumors [see Nonclinical Toxicology (13.2)]. Confirm evidence of a BRAF alteration prior to initiation of treatment with OJEMDA.

NONCLINICAL TOXICOLOGY

Carcinogenesis, 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).

Animal Toxicology and/or Pharmacology

In vitro, tovorafenib increased phosphorylation of ERK at clinically relevant concentrations in cells with neurofibromatosis Type 1-loss of function (NF1-LOF) suggesting activation, rather than inhibition, of the MAP kinase pathway. In an NF1 genetically engineered mouse model of plexiform neurofibroma without BRAF alteration, tovorafenib did not have antitumor activity, and while not statistically significant, an increase in tumor volume was noted in 2/12 mice (approximately 17%).

Patient Information for Ojemda

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.

Manufactured for: Day One Biopharmaceuticals, Inc. Brisbane CA 94005

Manufactured by (tablets): Quotient Sciences – Philadelphia LLC 3 Chelsea Parkway, Suite 305 Boothwyn PA 19061

Manufactured by (oral suspension): Quotient Sciences – Philadelphia LLC 3080 McCann Farm Dr. Garnet Valley, PA 19060 DAY101-USPI-082025v04

OVERDOSAGE

No information provided

Contraindications for Ojemda

No information provided

Clinical Pharmacology for Ojemda

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.

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/m² (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/m² orally once weekly (not to exceed 600 mg), a mean increase in the QT interval >20 milliseconds was not observed.

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/m² (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/m² (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 1.5x ULN and any AST], and mild-to-moderate renal impairment (eGFR) ≥ 30 mL/min/1.73 m² 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.

This Instructions for Use contains information on how to prepare, measure, and take or give a dose of OJEMDA for oral suspension.

Important information you need to know before preparing, measuring, and taking or giving a dose of OJEMDA for oral suspension.

• Read this Instructions for Use carefully before you prepare, measure, and take or give a dose of OJEMDA for oral suspension for the first time and each time you get a refill. There may be new information. This information does not take the place of talking with your or your child’s healthcare provider about your or your child’s medical treatment or condition.
• Your healthcare provider or pharmacist should show you how to prepare, measure, and take or give a dose of OJEMDA for oral suspension correctly. Talk to your healthcare provider or pharmacist if you have questions.
• Take or give OJEMDA for oral suspension exactly as your healthcare provider tells you to.
• You will receive the OJEMDA prescription in a box that contains a bottle with powder, a 20 mL oral dosing syringe, and a bottle adaptor. Contact your healthcare provider or pharmacist if you do not have one or more of these items.
• The bottle is made of glass. Do not use the bottle if it is broken or damaged. Contact your healthcare provider or pharmacist for a new bottle.
• Check the expiration date on the bottle and box. Contact your pharmacist if the expiration date has passed. Expired or unused product can be thrown away (disposed of) in your household trash.
• Only use room temperature water for preparing OJEMDA for oral suspension.
• Each dose of OJEMDA for oral suspension must be given within 15 minutes after the medicine has been prepared.
• Each bottle of OJEMDA for oral suspension is for single use only.
• See “How to throw away used bottles, expired or unused OJEMDA for oral suspension, and oral dosing syringes?” at the end of this Instructions for Use.

The OJEMDA box contains:
	Not included in the box: 1 empty clean cup room temperature water ENFIT syringe and ENFIT adaptor (if taking or giving OJEMDA oral suspension through a feeding tube)

• Always use the oral dosing syringe provided to make sure that you correctly measure your prescribed dose.
• The 20 mL oral dosing syringe is marked to help you correctly measure your prescribed dose of OJEMDA for oral suspension. The barrel of the oral dosing syringe has markings in milliliters (mL).
• Add exactly 14 mL of room temperature water to the bottle to prepare the OJEMDA for oral suspension. Only 12 mL of OJEMDA oral suspension will be taken or given from each prepared bottle.

Note: Your prescribed dose of OJEMDA for oral suspension may require preparing 2 bottles of the powder to give your prescribed dose of OJEMDA for oral suspension. If 2 bottles are required:

• • always add exactly 14 mL of room temperature water to each bottle, and
  • prepare, take or give the dose of OJEMDA for oral suspension from the first bottle and then repeat the same steps to prepare, take or give the dose of OJEMDA for oral suspension from the second bottle.
• OJEMDA for oral suspension can be taken or given by mouth using the 20 mL oral dosing syringe, or through a feeding tube with a minimum size of 12 French using an ENFIT syringe.
  • If you are taking or giving OJEMDA for oral suspension by mouth, follow Section A, Steps 1 to 19.
  • If taking or giving OJEMDA for oral suspension by a feeding tube, follow Section B, Steps 20 to 25.

Section A: Preparing, measuring, and taking or giving a dose of OJEMDA for oral suspension
Step 1. Wash and dry your hands before preparing, measuring, and taking or giving a dose of OJEMDA for oral suspension.
Step 2. Place your supplies on a clean, flat work surface.
Step 3. Fill a cup half-way with room temperature water. Do not use cold water.
Step 4. Remove air from the oral dosing syringe. Pull the plunger up into the oral dosing syringe as far as it will go, and then push the plunger back down into the oral dosing syringe as far as it will go. This will help to remove all the air inside.
Step 5. Place the oral dosing syringe tip in the water. Pull up on the plunger to draw water into the oral dosing syringe to the 14 mL mark. Note: Add exactly 14 ml of water to the bottle with powder.
Step 6. Remove the oral dosing syringe from the cup. Turn the oral dosing syringe tip upward and check for air bubbles. If large air bubbles appear in the oral dosing syringe, push the water back into the cup and then pull up on the plunger again to draw up the water to the 14 mL mark. Repeat Step 6 until there are no large air bubbles present. Small air bubbles are ok. Set the oral dosing syringe aside.
Step 7. Open the bottle with powder by pushing down firmly on the cap and turning it to the left (counterclockwise). Do not throw away the cap. Remove the Safety seal. Do not use the bottle with powder if the safety seal under the cap is broken or missing. Call your healthcare provider or pharmacist if the safety seal is broken.
Step 8. Insert the tip of the oral dosing syringe into the opening of the bottle. Push down on the plunger and inject 14 mL of water into the bottle. Remove the tip of the emptied oral dosing syringe from the bottle and set it aside. Right away, replace the cap back onto the bottle by pushing down while twisting the cap to the right (clockwise). Shake the bottle well for 60 seconds in all directions.
Step 9: Turn bottle upside down to check for any powder stuck to the inside of the bottle. If you still see powder in the bottle, continue to shake the bottle for another 15 seconds until you no longer see the powder inside the bottle. Do not shake the bottle for more than 2 minutes total time. Check the bottle to make sure all of the powder is no longer visible. If you still see powder in the bottle, contact your healthcare provider or pharmacist and ask for a new bottle.
Step 10. Turn the bottle upside down again and swirl for 30 seconds. Place the bottle on a flat, clean, work surface. Remove the cap and check that no solids are stuck in the bottle neck. If you see solids in the bottle neck, recap the bottle, turn the bottle upside down, and swirl for an additional 15 seconds. Allow the bottle to sit for 60 seconds to allow most of the foam to settle. Note: Foaming in the bottle will reduce the amount of OJEMDA for oral suspension.
Step 11. Open the bottle by firmly pressing down on the cap and turning it to the left (counterclockwise). Do not throw away the cap. Firmly insert the bottle adaptor into the bottle by pushing it tightly into the top of the bottle. The top edge of the bottle adaptor should be even with the bottle top. Do not remove the bottle adaptor after it is inserted into the bottle.
Step 12. Check your or your child’s dose in milliliters (mL) as prescribed by your healthcare provider. Pick up the oral dosing syringe again. Each mark on the oral dosing syringe is equal to 1 mL. Draw air into the oral dosing syringe by pulling the plunger out to your prescribed dose. For example, if your prescribed dose is 12 mL, you would draw the oral dosing syringe by pulling the plunger out to the 12 mL mark.
Step 13. Insert the tip of the oral dosing syringe into the bottle adaptor. The tip of the oral dosing syringe should fit snugly into the hole of the bottle adaptor. Keep the oral dosing syringe attached to the bottle. With the oral dosing syringe in place and holding the bottle where the oral dosing syringe tip inserts into bottle adaptor, swirl the oral suspension for 30 seconds.
Step 14. Inject the air from the oral dosing syringe into the bottle. Hold the oral dosing syringe in place and turn the bottle upside down. To measure the prescribed dose, keep the tip of the oral dosing syringe facing up and pull down on the plunger until the top of the plunger lines up with the prescribed dose in mLs.
Step 15. While the syringe is still in the bottle, remove any air bubbles in the oral dosing syringe by gently pushing the OJEMDA oral suspension back into the bottle and then pulling down on the plunger again to draw up your prescribed dose. Repeat Step 15 until you see that few or no air bubbles remain or if you draw up the wrong dose in the oral dosing syringe. Note: Only use up to 12 mL of OJEMDA oral suspension from each prepared bottle. If the prescribed dose is more than 12 mL (300 mg), split the dose as equally as possible between each prepared bottle. For example, if your dose is 13 mL, draw 6 mL from the first prepared bottle, and 7 mL from the second prepared bottle.
Step 16: Leave the tip of the oral dosing syringe in the bottle adaptor and carefully turn the bottle upright. Put the bottle onto your flat work surface again. Slowly remove the oral dosing syringe tip from the bottle adaptor by gently pulling straight up. Do not hold the oral dosing syringe by the plunger because the plunger may come out.
Step 17: Check again to be sure the top of the black stopper on the barrel of the oral dosing syringe is at your prescribed mL dose mark. If you do not have the correct prescribed mL dose, repeat Steps 15 to 17. If you are taking or giving a dose of OJEMDA for oral suspension by mouth, continue to Step 18. If you are taking or giving a dose of OJEMDA for oral suspension through a feeding tube, go to Section B. OJEMDA for oral suspension must be given within 15 minutes after prepared for use.
Step 18. You or your child should sit upright to take or give a dose of OJEMDA oral suspension. Place the tip of the oral dosing syringe towards the inside of the cheek in your or your child’s mouth. Slowly push the medicine into the mouth by pressing down on the plunger. Do not forcefully push the plunger. This may cause choking. Allow the child to swallow while giving OJEMDA. You or your child may drink liquids right away after swallowing the OJEMDA for oral suspension. Be sure to take or give the entire dose of OJEMDA for oral suspension. If 2 bottles of OJEMDA for oral suspension are required to take or give your prescribed dose, repeat Section A, Steps 1 to 18 for the second bottle. Throw away the prepared OJEMDA for oral suspension if it is not taken or given within 15 minutes.
Step 19: See Section C for instructions on “How to throw away used bottles, expired or unused OJEMDA for oral suspension, and oral dosing syringes”
Section B: Taking or giving a dose of OJEMDA or oral suspension through a feeding tube
Before giving a dose of OJEMDA for oral suspension through a feeding tube, read the following information and talk to your or your child’s healthcare provider before continuing to STEP 20: OJEMDA for oral suspension may be given through a feeding tube, as directed by your healthcare provider. Only use a feeding tube with a minimum size of 12 French. Always use the 20 mL oral dosing syringe (included in the box) to prepare each dose of OJEMDA for oral suspension in the bottle. Always use a 20 mL ENFIT syringe and an ENFIT adaptor (neither included in the box) to measure and give each dose of OJEMDA for oral suspension through the feeding tube.
Step 20. Flush the feeding tube according to the manufacturer’s instructions before giving a dose of OJEMDA for oral suspension.
Step 21: Follow Steps 1 to 11 in Section A to prepare the OJEMDA oral suspension using the 20 mL oral dosing syringe. Follow Steps 12 to 17 in Section A to draw up your or your child’s dose of OJEMDA for oral suspension using the ENFIT syringe and ENFIT adaptor.
Step 22: Connect the 20 mL ENFIT syringe containing OJEMDA for oral suspension to the feeding tube.
Step 23: Apply steady pressure to the plunger to give the entire dose of OJEMDA for oral suspension through the feeding tube.
Step 24: Flush the feeding tube after giving each dose of OJEMDA for oral suspension according to the manufacturer’s instructions. If 2 bottles are required, repeat Step 21 and give the remainder of the dose right away.
Step 25: Go to Section C for instructions on “How to throw away used bottles, expired or unused OJEMDA for oral suspension, and oral dosing syringes”
Section C: How to throw away used bottles, expired or unused OJEMDA for oral suspension, and oral dosing syringes
Throw away your used bottle(s), expired or unused OJEMDA for oral suspension, and oral dosing syringe(s) in your household trash. Do not re-use the oral dosing syringe(s).
How should I store OJEMDA?
Store the glass bottle containing OJEMDA for oral suspension at room temperature between 68°F to 77°F (20°C to 25°C). Keep OJEMDA for oral suspension, the oral dosing syringe, and all medicines out of the reach of children.
Manufactured for: Day One Biopharmaceuticals, Inc., Brisbane CA 94005 For more information, go to www.OJEMDA.com or call 1-855-DAY-1BIO (1-855-329-1246). © 2025 Day One Biopharmaceuticals, Inc. All rights reserved. OJEMDA is a trademark of Day One Biopharmaceuticals Inc. This Instructions for Use has been approved by the U.S. Food and Drug Administration.