Tovorafenib

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.

• 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) ].

• None . None.contraindicated

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.

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.

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.

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.

Metabolism

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%).

• Apr 23, 2024NDANDA218033Day One Biopharms
• Apr 23, 2024NDANDA217700Day One Biopharms

1. 1Rash249.1%
2. 2Fatigue207.6%
3. 3Accidental Underdose197.2%
4. 4Off Label Use186.8%
5. 5Disease Progression176.5%
6. 6Hair Colour Changes176.5%
7. 7Headache145.3%
8. 8Melanocytic Naevus134.9%
9. 9Blood Creatine Phosphokinase Increased114.2%
10. 10Acne103.8%
11. 11Intracranial Tumour Haemorrhage103.8%
12. 12Dermatitis Acneiform93.4%
13. 13Growth Retardation93.4%
14. 14Nausea83.0%
15. 15Blood Phosphorus Decreased62.3%

The 10 most recently updated of 16 ClinicalTrials.gov registrations naming Tovorafenib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis
  Recruiting · Phase 2 · Interventional · 48 enrolled · National Cancer Institute (NCI)
  NCT05828069updated 2026-06-12
• A Clinical Study Evaluating the Safety, Tolerability, and Effect on HIV Reservoir of Ibalizumab Combined With Chidamide (a Histone Deacetylase Inhibitor) in People Living With HIV
  Not yet recruiting · Phase 1 · Interventional · 18 enrolled · First Affiliated Hospital of Zhejiang University
  NCT07635992updated 2026-06-09
• Testing the Combination of Anti-cancer Drugs, Tovorafenib Plus Rituximab, in Patients With Hairy Cell Leukemia
  Recruiting · Phase 1 · Phase 2 · Interventional · 84 enrolled · National Cancer Institute (NCI)
  NCT06965114updated 2026-06-03
• A Study to Assess a Medicine Called Tovorafenib in Japanese Children and Young Adults With Brain Tumours
  Recruiting · Phase 1 · Interventional · 6 enrolled · Ipsen
  NCT07441707updated 2026-06-01
• DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
  Active not recruiting · Phase 3 · Interventional · 418 enrolled · Day One Biopharmaceuticals, Inc.
  NCT05566795updated 2026-05-14
• Tovorafenib for Treatment of Craniopharyngioma in Children and Young Adults
  Recruiting · Phase 2 · Interventional · 57 enrolled · Sabine Mueller, MD, PhD
  NCT05465174updated 2026-04-23
• Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)
  Not yet recruiting · Phase 2 · Interventional · 79 enrolled · Nationwide Children's Hospital
  NCT07206849updated 2026-04-08
• DAY101 In Gliomas and Other Tumors
  Completed · Phase 1 · Interventional · 44 enrolled · Karen D. Wright, MD
  NCT03429803updated 2026-02-19
• Tovorafenib (DAY101) Monotherapy for Patients With Melanoma and Other Solid Tumors
  Terminated · Phase 2 · Interventional · 23 enrolled · Day One Biopharmaceuticals, Inc.
  NCT04985604updated 2025-10-02
• Tovorafenib (DAY101) or in Combination With Pimasertib for Participants With Melanoma and Other Solid Tumors
  Terminated · Phase 1 · Interventional · 44 enrolled · Day One Biopharmaceuticals, Inc.
  NCT07121829updated 2025-08-14

Frequently asked questions

How does Tovorafenib work?

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.

What is Tovorafenib used for?

According to FDA labeling, Tovorafenib carries indications including: 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) ].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tovorafenib?

Tovorafenib is classified as B-Raf serine-threonine kinase (BRAF) inhibitors, Kinase Inhibitor, BRAF Serine/Threonine Kinase Inhibitors, Cytochrome P450 3A Inducers, Type II RAF Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Tovorafenib?

Tovorafenib is marketed under brand names including Ojemda.

What are the contraindications for Tovorafenib?

Tovorafenib labeling lists contraindications including: None . None.. Always consult the full prescribing information and a clinician.