Tovorafenib

Tovorafenib

506.29

C₁₇H₁₂Cl₂F₃N₇O₂S

1096708-71-2

6-amino-5-chloro-N-[(1R)-1-(5-{[5-chloro-4-(trifluoromethyl)pyridin-2-yl]carbamoyl}-1,3-thiazol-2-yl)ethyl]pyrimidine-4-carboxamide

4/23/2024 FDA APROVED, To treat relapsed or refractory pediatric low-grade glioma, Ojemda

• AMG 2112819
• BIIB 024
• BIIB-024
• BIIB024
• DAY 101
• DAY-101
• DAY101
• MLN 2480
• MLN-2480
• MLN2480
• TAK 580
• TAK-580
• TAK580

Tovorafenib, sold under the brand name Ojemda, is a medication used for the treatment of glioma.^[1] It is a kinase inhibitor.^[1]

The most common adverse reactions include rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection.^[2] The most common grade 3 or 4 laboratory abnormalities include decreased phosphate, decreased hemoglobin, increased creatinine phosphokinase, increased alanine aminotransferase, decreased albumin, decreased lymphocytes, decreased leukocytes, increased aspartate aminotransferase, decreased potassium, and decreased sodium.^[2]

It was approved for medical use in the United States in April 2024,^[1][2][3][4] and is the first approval of a systemic therapy for the treatment of people with pediatric low-grade glioma with BRAF rearrangements, including fusions.^[2]

Medical uses

Tovorafenib is indicated for the treatment of people six months of age and older with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.^[1][2]

History

Efficacy was evaluated in 76 participants enrolled in FIREFLY-1 (NCT04775485), a multicenter, open-label, single-arm trial in participants with relapsed or refractory pediatric low-grade glioma harboring an activating BRAF alteration detected by a local laboratory who had received at least one line of prior systemic therapy.^[2] Participants were required to have documented evidence of radiographic progression and at least one measurable lesion.^[2] Participants with tumors harboring additional activating molecular alterations (e.g., IDH1/2 mutations, FGFR mutations) or with a known or suspected diagnosis of neurofibromatosis type 1 were excluded.^[2] Participants received tovorafenib based on body surface area (range: 290 to 476 mg/m2, up to a maximum dose of 600 mg) once weekly until they experienced disease progression or unacceptable toxicity.^[2] The US Food and Drug Administration (FDA) granted the application for tovorafenib priority review, breakthrough therapy, and orphan drug designations.^[2]

Society and culture

Names

Tovorafenib is the international nonproprietary name.^[5]

SYN

PATENT

 WO 2009/006389

Huang et al., Angew. Chem. int. Ed. (2016), 55, 5309-5317

 Jiang Xiao-bin et al., Org. Lett. (2003), 5, 1503

10Da

SYN

Patent

https://patentscope.wipo.int/search/en/detail.jsf?docId=US131345763&_cid=P22-LW02NH-45076-1

PATENT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US201396258&_cid=P22-LW02NH-45076-1

PATENT

References

1. ^ Jump up to:^{a b c d e} “Archived copy” (PDF). Archived (PDF) from the original on 24 April 2024. Retrieved 24 April 2024.
2. ^ Jump up to:^{a b c d e f g h i j} “FDA grants accelerated approval to tovorafenib for patients with relapsed or refractory BRAF-altered pediatric low-grade glioma”. U.S. Food and Drug Administration (FDA). 23 April 2024. Archived from the original on 23 April 2024. Retrieved 25 April 2024.  This article incorporates text from this source, which is in the public domain.
3. ^ “Novel Drug Approvals for 2024”. U.S. Food and Drug Administration (FDA). 29 April 2024. Archived from the original on 30 April 2024. Retrieved 30 April 2024.
4. ^ “Day One’s Ojemda (tovorafenib) Receives US FDA Accelerated Approval for Relapsed or Refractory BRAF-altered Pediatric Low-Grade Glioma (pLGG), the Most Common Form of Childhood Brain Tumor”. Day One Biopharmaceuticals (Press release). 23 April 2024. Archived from the original on 23 April 2024. Retrieved 24 April 2024.
5. ^ World Health Organization (2022). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 88”. WHO Drug Information. 36 (3). hdl:10665/363551.

External links

• “Tovorafenib”. NCI Drug Dictionary.
• “Tovorafenib (Code C106254)”. NCI Thesaurus.
• Clinical trial number NCT04775485 for “A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors (FIREFLY-1)” at ClinicalTrials.gov

////////Tovorafenib, Ojemda, FDA 2024. APPROVALS 2024, AMG 2112819, BIIB 024, BIIB-024, BIIB024, DAY 101, DAY-101, DAY101, MLN 2480, MLN-2480, MLN2480, TAK 580, TAK-580, TAK580