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OJEMDA (tovorafenib) logo: 100 mg tablets 25 mg/mL for oral suspension

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Prescribing Information

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Safety

Warnings and Precautions

Warnings and precautions for OJEMDA1,2

The safety population described in warnings and precautions reflects exposure to OJEMDA taken orally once weekly at a dose based on body surface area in 143 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.

Hemorrhage

  • Hemorrhage, including major hemorrhage defined as symptomatic bleeding in a critical area or organ, can occur with OJEMDA
  • In a pooled safety population:
    • Hemorrhagic events in 39% of 175 patients
      • Epistaxis in 27% of patients
      • ITH in 11% of patients
      • Serious bleeding events in 6% of patients (0.6% grade 5; n=1)
    • Advise patients and caregivers of the risk of hemorrhage during treatment
  • Monitor for signs and symptoms of hemorrhage, evaluate as clinically indicated, and consult and follow dosing modifications

Skin toxicity including photosensitivity

  • OJEMDA can cause rash, including maculopapular rash and photosensitivity
  • In a pooled safety population:
    • Rash occurred in 71% of 175 patients treated with OJEMDA (12% grade 3)
    • Dermatitis acneiform in 33% of patients treated with OJEMDA (0.6% grade 3; n=1)
  • Monitor for new or worsening skin reactions. Consider dermatologic consultation and initiate supportive care as clinically indicated
  • Photosensitivity
    • In the pooled safety population:
      • Photosensitivity occurred in 13% of 175 patients
        • Grade 3 events occurred 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, and to consult with HCPs and follow dosing modifications based on severity of AR

Hepatotoxicity

  • OJEMDA can cause hepatotoxicity
  • In a pooled safety population:
    • Increased ALT in 43% of 175 patients (5% grade 3)
    • Increased AST in 75% of 175 patients (2% grade 3)
  • The median time to onset of increased ALT or AST was 14 days (range: 3 to 898 days)
  • Increased bilirubin occurred in 23% of patients (0.6% grade 3; n=1)
  • Monitor liver function tests (including ALT, AST, and bilirubin) before initiation of OJEMDA, one month after initiation, and then every 3 months thereafter and as clinically indicated

Effect on growth

  • OJEMDA can cause reductions in growth velocity
  • In FIREFLY-1, treatment-emergent adverse effects on growth were reported in:
    • 46% of 133 patients 18 years or younger
    • 35% were grade 3 or higher
  • Reduced growth velocity resulted in:
    • Dose reduction in 2% of patients
    • Dose interruption in 5% of patients
    • 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
  • Median annualized growth velocity ranged from 0.86 to 1.8 cm/year
    • 17 of 81 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

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
  • Advise pregnant women and females of reproductive potential of the potential risk to a fetus and to use effective nonhormonal contraception during treatment and for 28 days after the last dose
  • Advise male patients with female partners of reproductive potential to use effective nonhormonal contraception during treatment and for 2 weeks after the last dose

NF1 associated tumors

  • Based on nonclinical data, tovorafenib may promote tumor growth in patients with NF1 tumors
  • Confirm evidence of BRAF alteration prior to initiation of treatment

Once-weekly oral dosing, taken with or without food

See how to take OJEMDA

Adverse Reactions

OJEMDA was generally well tolerated with management strategies1,2

The majority of adverse reactions were grade 1 or 21

  • The safety of OJEMDA was evaluated in 137 patients with R/R pLGG harboring a BRAF alteration2
  • These data are based on May 10, 2024 data cutoff and are not reflected in the Prescribing Information
  • Serious adverse reactions occurred in 55% of patients who received OJEMDA. Serious adverse reactions in >3% of patients included pyrexia (11%), viral infection (10%), hemorrhage (10%), hydrocephalus (7%), reduction in growth velocity (7%), seizure (7%), vomiting (7%), headache (4%), pneumonia (4%), appendicitis (4%), hyponatremia (4%), and sepsis (4%)

Adverse reactions occurring in ≥20% of pediatric patients1

OJEMDA (N=137)

All grades

Grade 3 or 4

Skin and subcutaneous tissue disorders

Rash

83%

12%

Hair color changes

77%

0%

Dry skin

47%

0%

Dermatitis acneiform

38%

0.7%

Pruritus

28%

1%

Alopecia

20%

0%

General disorders

Fatigue

61%

4%

Pyrexia

47%

7%

Edema

34%

0%

Infections and infestations

Viral infection

63%

10%

Upper respiratory tract infection

36%

1%

Paronychia

30%

1%

Gastrointestinal disorders

Vomiting

56%

7%

Nausea

37%

0%

Constipation

36%

0.7%

Abdominal pain

29%

0.7%

Stomatitis

28%

0%

Diarrhea

26%

1%

Nervous system disorders

Headache

53%

2%

Vascular disorders

Hemorrhage

47%

6%*

Musculoskeletal and connective tissue disorders

Decreased growth velocity

46%

35%

Pain in extremity

20%

0.7%

Metabolism and nutrition disorders

Decreased appetite

30%

4%

Decreased weight

26%

1%

  • Clinically relevant adverse reactions occurring in <20% of patients treated with OJEMDA were skin discoloration, myalgia, photosensitivity reaction, arthralgia, and flushing

*Includes one grade 5 event.

Cardiovascular, ocular, and skin events NOT observed as of data cutoff†

Uveitis, retinal detachment, or retinal vascular occlusion were not observed1

No drug-related adverse reactions associated with impaired cardiac function were observed1

No patients experienced life-threatening skin reactions, and no keratoacanthomas developed1

Cardiac and ocular monitoring are not required1

†These data are based on May 10, 2024 data cutoff.

Lab Abnormalities

Safety and tolerability, including lab abnormalities, were assessed in FIREFLY-11

These data are based on May 10, 2024 data cutoff and are not reflected in the Prescribing Information.

Select laboratory abnormalities (≥20%) that worsened from baseline1

OJEMDA*

All grades

Grade 3 or 4

Hematology

Decreased hemoglobin

93%

15%

Decreased lymphocytes

53%

3%

Increased eosinophils

48%

0%

Decreased leukocytes

34%

1%

Increased lymphocytes

32%

0%

Chemistry

Decreased phosphate

88%

27%

Increased AST

86%

2%

Increased creatine phosphokinase

86%

13%

Increased LDH

74%

0%

Decreased potassium

55%

3%

Increased ALT

51%

6%

Decreased albumin

31%

0%

Increased bilirubin

23%

1%

Decreased sodium

20%

1%

*The denominator for each laboratory parameter is based on the number of patients with a baseline and posttreatment laboratory value available, which ranged from 67 to 137 patients.

Severity as defined by National Cancer Institute CTCAE v5.0.

Increased creatine phosphokinase was a clinically important laboratory abnormality that worsened from baseline in patients treated with OJEMDA.1

In the clinical trial, most laboratory abnormalities had no clinical manifestations and did not require intervention1

To learn more about adverse reactions and management guidelines

Download the Dosing and AR Management Guide

Dose Modification Rates

Dose modifications or interruptions may help with adverse reactions management1

These data are based on May 10, 2024 data cutoff and are not reflected in the Prescribing Information.

32

%

Dosage
reduction

(n=44/137)

Adverse reactions that required dosage reduction in ≥2% of patients included rash, fatigue, decreased appetite, and reduction in growth velocity.

66

%

Dosage
interruption

(n=90/137)

Adverse reactions that required dosage interruption in ≥5% of patients included rash, pyrexia, viral infection, vomiting, fatigue, hydrocephalus, reduction in growth velocity, hemorrhage, nausea, ALT increased, and headache.

Low rate of treatment discontinuation due to adverse reactions observed in the trial

11

%

Discontinuation rate

(n=15/137)

Adverse reactions that resulted in permanent discontinuation in more than one patient were tumor hemorrhage and reduction in growth velocity.

The median duration of dose interruption due to an adverse reaction was 3 weeks1

ALT=alanine aminotransferase; AR=adverse reaction; AST=aspartate aminotransferase; BRAF=v-Raf murine sarcoma viral oncogene homolog B1; CTCAE=Common Terminology Criteria for Adverse Events; ITH=intratumoral hemorrhage; LDH=lactate dehydrogenase; LGG=low-grade glioma; NF1=neurofibromatosis type 1; pLGG=pediatric low-grade glioma; RAF=rapidly accelerated fibrosarcoma; R/R=relapsed/refractory.

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IMPORTANT SAFETY INFORMATION
INDICATION

Warnings and Precautions

Hemorrhage

Hemorrhage, including major hemorrhage defined as symptomatic bleeding in a critical area or organ, can occur with OJEMDA. 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.

Skin Toxicity Including Photosensitivity

OJEMDA can cause rash, including maculopapular rash and photosensitivity. 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.

Photosensitivity

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.

Hepatotoxicity

OJEMDA can cause hepatotoxicity. 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.

Effect on Growth

OJEMDA can cause reductions in growth velocity. Growth velocity improved after interruption of treatment with OJEMDA. Routinely monitor patient growth during treatment with OJEMDA.

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. 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. 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.

NF1 Associated Tumors

Based on nonclinical data in NF1 models without BRAF alterations, tovorafenib may promote tumor growth in patients with NF1 tumors. Confirm evidence of a BRAF alteration prior to initiation of treatment with OJEMDA.

Adverse Reactions

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.

INDICATION

OJEMDATM (tovorafenib) 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Please see full Prescribing Information.

References