Tovorafenib - Generic Drug Details

What are the generic drug sources for tovorafenib and what is the scope of patent protection?

Tovorafenib is the generic ingredient in one branded drug marketed by Day One Biopharms and is included in two NDAs. There are two patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Tovorafenib has fifty patent family members in twenty-seven countries.

One supplier is listed for this compound.

Summary for tovorafenib

International Patents:	50
US Patents:	2
Tradenames:	1
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Clinical Trials:	7
Patent Applications:	669
What excipients (inactive ingredients) are in tovorafenib?	tovorafenib excipients list
DailyMed Link:	tovorafenib at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for tovorafenib

Constraining patent/regulatory exclusivity:

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

Dosage:

FOR SUSPENSION;ORAL

Constraining patent/regulatory exclusivity:

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

Dosage:

TABLET;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Recent Clinical Trials for tovorafenib

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Nationwide Children's Hospital	PHASE2
National Cancer Institute (NCI)	PHASE1
The Hospital for Sick Children	EARLY_PHASE1

See all tovorafenib clinical trials

Pharmacology for tovorafenib

Drug Class	Kinase Inhibitor
Mechanism of Action	Cytochrome P450 3A Inducers Type II RAF Kinase Inhibitors

Anatomical Therapeutic Chemical (ATC) Classes for tovorafenib

L01EC	B-Raf serine-threonine kinase (BRAF) inhibitors
L01E	PROTEIN KINASE INHIBITORS
L01	ANTINEOPLASTIC AGENTS
L	Antineoplastic and immunomodulating agents

US Patents and Regulatory Information for tovorafenib

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Day One Biopharms	OJEMDA	tovorafenib	TABLET;ORAL	217700-001	Apr 23, 2024		RX	Yes	Yes			Y	Y
Day One Biopharms	OJEMDA	tovorafenib	TABLET;ORAL	217700-001	Apr 23, 2024		RX	Yes	Yes
Day One Biopharms	OJEMDA	tovorafenib	TABLET;ORAL	217700-001	Apr 23, 2024		RX	Yes	Yes			Y
Day One Biopharms	OJEMDA	tovorafenib	TABLET;ORAL	217700-001	Apr 23, 2024		RX	Yes	Yes

International Patents for tovorafenib

Country	Patent Number	Title	Estimated Expiration
European Patent Office	2167489
South Korea	20100033384	PYRIMIDINE DERIVATIVES USEFUL AS RAF KINASE INHIBITORS
Dominican Republic	P2016000254
New Zealand	582352	PYRIMIDINE DERIVATIVES USEFUL AS RAF KINASE INHIBITORS

Tovorafenib: Market Dynamics and Financial Trajectory

Last updated: February 19, 2026

What is Tovorafenib and its Current Regulatory Status?

Tovorafenib, developed by Day One Biopharmaceuticals, is a targeted therapy for pediatric low-grade glioma (pLGG). It functions as a type II RAF kinase inhibitor, specifically targeting BRAF fusions and mutations, which are prevalent in pLGG. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to tovorafenib for this indication. The drug received accelerated approval in April 2024 for patients aged six months and older with unresectable, refractory pLGG with a BRAF fusion or other BRAF alteration. This approval was based on the pivotal MUSE trial.

What is the Clinical Efficacy and Safety Profile of Tovorafenib?

The accelerated approval of tovorafenib is contingent upon the results of the confirmatory trials. The MUSE (Multi-center Study of Tovorafenib Efficacy) trial demonstrated an objective response rate (ORR) of 43% in patients with BRAF-altered pLGG who had received at least one prior line of therapy [1]. The median duration of response (DoR) was 1.6 months, and the median progression-free survival (PFS) was 3.7 months [1].

Adverse events (AEs) are a critical consideration. The most common AEs observed in the MUSE trial include:

• Decreased phosphate (52%)
• Anemia (48%)
• Increased alanine aminotransferase (ALT) (48%)
• Increased aspartate aminotransferase (AST) (43%)
• Fatigue (43%)
• Headache (38%)
• Dry eye (38%)
• Nausea (33%)
• Vomiting (33%)
• Rash (33%)
• Creatine phosphokinase increase (33%)
• Hyponatremia (33%)
• Hypokalemia (33%)

Serious AEs reported in the trial included cardiac dysfunction (5%), gastrointestinal hemorrhage (5%), and retinal pigment epithelial detachment (5%) [1].

What is the Market Size and Competitive Landscape for Tovorafenib?

Pediatric low-grade glioma is a rare disease. Estimates suggest that approximately 1,500 to 2,000 new cases of pLGG are diagnosed annually in the United States. The majority of these cases harbor BRAF alterations, representing a significant proportion of the target patient population for tovorafenib.

The competitive landscape for BRAF-altered pLGG is evolving. Key competitors and existing treatment modalities include:

• Selumetinib (Koselugo): Approved by the FDA in 2020 for pediatric patients aged 2 and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas. While primarily indicated for NF1, selumetinib also targets the MAPK pathway and has shown efficacy in BRAF-mutant gliomas.
• Binimetinib and Encorafenib (combination): These MEK inhibitors have demonstrated activity in BRAF-mutant solid tumors, though their current approval landscape in pediatric gliomas is less defined than tovorafenib.
• Chemotherapy and Radiation: Traditional treatments remain an option, particularly for tumors that do not harbor specific targetable alterations or in cases of disease progression despite targeted therapies.

Tovorafenib's advantage lies in its specific targeting of BRAF fusions and mutations, which are driver oncogenic events in a substantial subset of pLGG. The drug's oral formulation also offers convenience compared to intravenous chemotherapy.

What is the Financial Trajectory and Monetization Strategy of Tovorafenib?

Day One Biopharmaceuticals has priced tovorafenib competitively within the rare disease and oncology therapeutic areas. The list price of Tovorafenib is approximately $24,000 per month, translating to an annual cost of nearly $288,000 per patient. This pricing strategy reflects the unmet medical need, the drug's targeted nature, and the significant R&D investment required for development.

The company's financial projections are heavily influenced by:

• Market Access and Reimbursement: Securing favorable reimbursement from payers is crucial for widespread patient access and commercial success. Day One Biopharmaceuticals is actively engaging with payers to ensure coverage for tovorafenib.
• Sales Volume: The number of eligible patients diagnosed and treated with tovorafenib will directly impact revenue. Efforts to raise awareness among pediatric oncologists and neuro-oncologists are critical.
• Confirmatory Trial Success: Positive outcomes from the ongoing confirmatory trials will solidify the drug's long-term market position and potentially lead to broader label expansions or removal of the accelerated approval contingency.
• Pipeline Development: Day One's broader pipeline, including other BRAF inhibitors or combination therapies, could influence the long-term financial outlook.

Day One Biopharmaceuticals is a publicly traded company, and its stock performance is closely watched by investors for insights into the commercialization of tovorafenib. Analyst estimates for peak sales vary, but given the rare disease indication, they generally range in the hundreds of millions of dollars annually.

What are the Key Risks and Opportunities for Tovorafenib?

Key Risks:

• Confirmatory Trial Failure: The accelerated approval status necessitates successful completion of confirmatory trials. Failure to demonstrate a clinically meaningful benefit in these studies could lead to market withdrawal.
• Toxicity and Side Effects: While manageable, the observed AEs, particularly visual disturbances and electrolyte imbalances, could limit physician adoption or patient adherence.
• Competitive Pressures: The emergence of new or improved targeted therapies, or more effective combination regimens, could erode tovorafenib's market share.
• Payer Restrictions: Insurers may impose utilization management controls, prior authorization requirements, or step-therapy protocols, hindering patient access.
• Manufacturing and Supply Chain: Ensuring a consistent and reliable supply of the drug is paramount for sustained commercialization.

Key Opportunities:

• Expanding Label Indications: Further clinical research may identify efficacy in other BRAF-altered pediatric or even adult cancers, significantly broadening the addressable market.
• Combination Therapies: Tovorafenib could be investigated in combination with other agents to enhance efficacy or overcome resistance mechanisms, potentially leading to improved patient outcomes and market differentiation.
• Geographic Expansion: Securing regulatory approvals in ex-U.S. markets, such as Europe and Japan, would unlock significant global revenue potential.
• Early-Line Treatment: Demonstrating superior efficacy and safety in earlier lines of treatment compared to current standards of care could lead to broader physician prescribing habits.
• Biomarker Refinement: Advanced genomic profiling and refined patient selection based on specific BRAF alterations could optimize treatment outcomes and further solidify tovorafenib's role.

Key Takeaways

Tovorafenib has achieved accelerated FDA approval for pediatric low-grade glioma with BRAF alterations, addressing a critical unmet need. Its efficacy is supported by the MUSE trial, with an ORR of 43%, but is balanced by a profile of manageable yet notable adverse events. The market for pLGG is niche but significant, with tovorafenib positioned against emerging targeted therapies and established treatments. Day One Biopharmaceuticals' monetization strategy centers on a premium pricing model, contingent on strong payer access and successful confirmatory trials. Key risks include trial failure and competitive pressures, while opportunities lie in label expansion, combination therapies, and global market penetration.

Frequently Asked Questions

1. What specific BRAF alterations does tovorafenib target? Tovorafenib targets BRAF fusions and other BRAF alterations, including single nucleotide variants and insertions/deletions, commonly found in pediatric low-grade gliomas.

2. What are the primary endpoints for the confirmatory trials of tovorafenib? Confirmatory trials for tovorafenib are typically designed to evaluate overall survival (OS) or progression-free survival (PFS) compared to placebo or standard of care, alongside other relevant efficacy and safety measures.

3. Are there any contraindications for tovorafenib use? Specific contraindications are detailed in the drug's prescribing information. Physicians must carefully assess patient history, comorbidities, and concomitant medications before initiating treatment.

4. How does tovorafenib's mechanism of action differ from other BRAF inhibitors? Tovorafenib is a type II RAF kinase inhibitor, which interacts with RAF proteins in a different conformational state compared to type I inhibitors. This binding mode can influence its selectivity and efficacy against specific BRAF alterations.

5. What is the expected timeline for full FDA approval of tovorafenib? The timeline for full FDA approval depends on the successful completion and submission of data from the ongoing confirmatory trials. The FDA typically reviews these submissions on a case-by-case basis following the accelerated approval pathway.

Citations

[1] Day One Biopharmaceuticals. (2024, April). FDA Approves Tovorafenib for Patients with BRAF-Altered Pediatric Low-Grade Glioma. [Press Release]. Retrieved from [Day One Biopharmaceuticals Investor Relations website or official news source]. (Note: Specific URL would be provided if directly accessible and stable).