OGSIVEO
Generic: NIROGACESTAT
Basic Information
Manufacturer
SpringWorks Therapeutics, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
f172e6ff-3190-41b0-b95a-58a7ef9e9e1e
Indications & Usage
1 INDICATIONS AND USAGE OGSIVEO is indicated for adult patients with progressing desmoid tumors who require systemic treatment.
OGSIVEO is a gamma secretase inhibitor indicated for adult patients with progressing desmoid tumors who require systemic treatment.
( 1 )
OGSIVEO is a gamma secretase inhibitor indicated for adult patients with progressing desmoid tumors who require systemic treatment.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Diarrhea [ see Warnings and Precautions ( 5.1 )] Ovarian Toxicity [ see Warnings and Precautions ( 5.2 )] Hepatotoxicity [see Warnings and Precautions ( 5.3 )] Non-Melanoma Skin Cancers [see Warnings and Precautions ( 5.4 )] Electrolyte Abnormalities [ see Warnings and Precautions ( 5.5 )] The most common ( > 15 %) adverse reactions are diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection and dyspnea.
( 6.1 ) The most common laboratory abnormalities (≥15%) are decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact SpringWorks Therapeutics at 1-888-400-7989 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.
The safety of OGSIVEO was evaluated in 69 patients enrolled in DeFi with progressing desmoid tumor [see Clinical Studies ( 14 ) ].
Patients received OGSIVEO 150 mg orally twice daily or placebo orally twice daily until disease progression or unacceptable toxicity.
The median duration of exposure to OGSIVEO was 20.6 months (range: 0.3 to 33.6).
Serious adverse reactions occurred in 20% of patients who received OGSIVEO.
Serious adverse reactions occurring in ≥ 2% of patients were ovarian toxicity (4%).
Permanent discontinuation of OGSIVEO due to an adverse reaction occurred in 20% of patients.
Adverse reactions which resulted in permanent discontinuation of OGSIVEO in ≥ 2% of patients were diarrhea, ovarian toxicity, increased ALT, and increased AST.
Dosage interruptions of OGSIVEO due to an adverse reaction occurred in 51% of patients.
Adverse reactions which required dosage interruption in ≥ 2% of patients included diarrhea, rash, stomatitis, hypophosphatemia, fatigue, folliculitis, nausea, and ovarian toxicity.
Dose reductions of OGSIVEO due to an adverse reaction occurred in 42% of patients.
Adverse reactions which required dose reductions in ≥ 2% of patients included diarrhea, rash, stomatitis, hypophosphatemia, folliculitis, hidradenitis, and ovarian toxicity.
The most common (≥ 15% with a difference between arms of ≥ 5% compared to placebo) adverse reactions that occurred in patients receiving OGSIVEO were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection and dyspnea.
Table 2 summarizes the adverse reactions that occurred in DeFi.
Table 2.
Adverse Reactions (≥ 15%) in Patients with Desmoid Tumor Who Received OGSIVEO with a Difference Between Arms of ≥ 5% Compared to Placebo on DeFi Adverse Reaction OGSIVEO (N = 69) Placebo (N = 72) All Grades (%) Grade 3 (%) All Grades (%) Grade 3 (%) Gastrointestinal Diarrhea 84 16 35 1.4 Nausea 54 1.4 39 0 Stomatitis a 39 4 4 0 Abdominal Pain a 22 1.4 14 1.4 Reproductive S ystem Ovarian toxicity a , b 75 c 0 0 0 Skin and S ubcutaneous T issue Rash a 68 6 14 0 Alopecia 19 0 1.4 0 General Fatigue a 54 2.9 38 0 Nervous S ystem Headache a 30 0 15 0 Respiratory Cough a 20 0 6 0 Dyspnea 16 0 6 0 Infections Upper respiratory tract 17 0 2.8 0 infection a a Includes multiple related composite terms.
b Investigator assessment of ovarian toxicity included ovarian failure, premature menopause, amenorrhea, and menopause c The number of females of reproductive potential in each arm is used as the denominator (OGSIVEO N = 36, Placebo N = 37).
Clinically relevant adverse reactions occurring in < 15% of patients receiving OGSIVEO in DeFi included non-melanoma skin cancers, epistaxis, hidradenitis suppurativa, folliculitis, influenza-like illness, and renal tubular disorder.
Table 3 summarizes laboratory abnormalities in DeFi.
Table 3.
Laboratory Abnormalities (≥15%) that Worsened from Baseline in Patients with Desmoid Tumor Who Received OGSIVEO in DeFi Laboratory Abnormality OGSIVEO Placebo All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Decreased phosphate a ,b 65 Not Applicable 11 Not Applicable Increased urine glucose c ,d 51 Not Applicable 0 Not Applicable Increased urine protein c 40 0 25 0 Increased aspartate aminotransferase a 33 2.9 18 1.4 Increased alanine aminotransferase a 30 6 21 1.4 Decreased potassium a 22 1.4 4.2 0 a The denominator used to calculate the rate was 69 for nirogacestat and 72 for placebo based on the number of patients with a baseline value and at least one post-treatment value.
b CTCAE Version 5.0 does not include numeric thresholds for grading of hypophosphatemia; all grades represent patients with lab value < Lower Limit of Normal (LLN).
c The denominator used to calculate the rate was 68 for nirogacestat and 69 for placebo based on the number of patients with a baseline value and at least one post-treatment value.
d CTCAE Version 5.0 does not include numeric thresholds for grading of increased urine glucose.
( 6.1 ) The most common laboratory abnormalities (≥15%) are decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact SpringWorks Therapeutics at 1-888-400-7989 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.
The safety of OGSIVEO was evaluated in 69 patients enrolled in DeFi with progressing desmoid tumor [see Clinical Studies ( 14 ) ].
Patients received OGSIVEO 150 mg orally twice daily or placebo orally twice daily until disease progression or unacceptable toxicity.
The median duration of exposure to OGSIVEO was 20.6 months (range: 0.3 to 33.6).
Serious adverse reactions occurred in 20% of patients who received OGSIVEO.
Serious adverse reactions occurring in ≥ 2% of patients were ovarian toxicity (4%).
Permanent discontinuation of OGSIVEO due to an adverse reaction occurred in 20% of patients.
Adverse reactions which resulted in permanent discontinuation of OGSIVEO in ≥ 2% of patients were diarrhea, ovarian toxicity, increased ALT, and increased AST.
Dosage interruptions of OGSIVEO due to an adverse reaction occurred in 51% of patients.
Adverse reactions which required dosage interruption in ≥ 2% of patients included diarrhea, rash, stomatitis, hypophosphatemia, fatigue, folliculitis, nausea, and ovarian toxicity.
Dose reductions of OGSIVEO due to an adverse reaction occurred in 42% of patients.
Adverse reactions which required dose reductions in ≥ 2% of patients included diarrhea, rash, stomatitis, hypophosphatemia, folliculitis, hidradenitis, and ovarian toxicity.
The most common (≥ 15% with a difference between arms of ≥ 5% compared to placebo) adverse reactions that occurred in patients receiving OGSIVEO were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection and dyspnea.
Table 2 summarizes the adverse reactions that occurred in DeFi.
Table 2.
Adverse Reactions (≥ 15%) in Patients with Desmoid Tumor Who Received OGSIVEO with a Difference Between Arms of ≥ 5% Compared to Placebo on DeFi Adverse Reaction OGSIVEO (N = 69) Placebo (N = 72) All Grades (%) Grade 3 (%) All Grades (%) Grade 3 (%) Gastrointestinal Diarrhea 84 16 35 1.4 Nausea 54 1.4 39 0 Stomatitis a 39 4 4 0 Abdominal Pain a 22 1.4 14 1.4 Reproductive S ystem Ovarian toxicity a , b 75 c 0 0 0 Skin and S ubcutaneous T issue Rash a 68 6 14 0 Alopecia 19 0 1.4 0 General Fatigue a 54 2.9 38 0 Nervous S ystem Headache a 30 0 15 0 Respiratory Cough a 20 0 6 0 Dyspnea 16 0 6 0 Infections Upper respiratory tract 17 0 2.8 0 infection a a Includes multiple related composite terms.
b Investigator assessment of ovarian toxicity included ovarian failure, premature menopause, amenorrhea, and menopause c The number of females of reproductive potential in each arm is used as the denominator (OGSIVEO N = 36, Placebo N = 37).
Clinically relevant adverse reactions occurring in < 15% of patients receiving OGSIVEO in DeFi included non-melanoma skin cancers, epistaxis, hidradenitis suppurativa, folliculitis, influenza-like illness, and renal tubular disorder.
Table 3 summarizes laboratory abnormalities in DeFi.
Table 3.
Laboratory Abnormalities (≥15%) that Worsened from Baseline in Patients with Desmoid Tumor Who Received OGSIVEO in DeFi Laboratory Abnormality OGSIVEO Placebo All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Decreased phosphate a ,b 65 Not Applicable 11 Not Applicable Increased urine glucose c ,d 51 Not Applicable 0 Not Applicable Increased urine protein c 40 0 25 0 Increased aspartate aminotransferase a 33 2.9 18 1.4 Increased alanine aminotransferase a 30 6 21 1.4 Decreased potassium a 22 1.4 4.2 0 a The denominator used to calculate the rate was 69 for nirogacestat and 72 for placebo based on the number of patients with a baseline value and at least one post-treatment value.
b CTCAE Version 5.0 does not include numeric thresholds for grading of hypophosphatemia; all grades represent patients with lab value < Lower Limit of Normal (LLN).
c The denominator used to calculate the rate was 68 for nirogacestat and 69 for placebo based on the number of patients with a baseline value and at least one post-treatment value.
d CTCAE Version 5.0 does not include numeric thresholds for grading of increased urine glucose.