Application 211192

Type
NDA
Sponsor
AGIOS PHARMS INC

Application Products#

Product, Drug, Ingredient table
ProductDrugIngredientFormStrengthReference drugReference standard
001TIBSOVOIVOSIDENIBTABLET;ORAL250MGYesYes

Orange Book products#

Application-product, Trade name, Ingredient table
Application-productTrade nameIngredientStrengthDosage form / routeTE codesRLD / RSApproval date
N211192-001TIBSOVOIVOSIDENIB250MGTABLET / ORALRLD, RS2018-07-20

Orange Book patents#

Application-product, Patent, Expiration table
Application-productPatentExpirationUse codeCoverage / statusSubmission date
N211192-001106101252030-06-21U-33852020-04-28
N211192-001106101252030-06-21U-27852020-04-28
N211192-001106101252030-06-21U-27842020-04-28
N211192-001107177642033-01-18U-32152021-09-24
N211192-001116676732033-01-18U-37422023-11-17
N211192-00198502772033-01-18U-2350Drug substance, Drug product2018-08-13
N211192-00198502772033-01-18U-3213Drug substance, Drug product2018-08-13
N211192-00198502772033-01-18U-3386Drug substance, Drug product2018-08-13
N211192-00198502772033-01-18U-3742Drug substance, Drug product2018-08-13
N211192-00198502772033-01-18U-2534Drug substance, Drug product2018-08-13
N211192-00198502772033-01-18U-2533Drug substance, Drug product2018-08-13
N211192-00194747792033-08-19U-3742Drug substance, Drug product2018-08-13
N211192-00194747792033-08-19U-2350Drug substance, Drug product2018-08-13
N211192-00194747792033-08-19U-3213Drug substance, Drug product2018-08-13
N211192-00194747792033-08-19U-3386Drug substance, Drug product2018-08-13
N211192-00194747792033-08-19U-2534Drug substance, Drug product2018-08-13
N211192-00194747792033-08-19U-2533Drug substance, Drug product2018-08-13
N211192-001104491842035-03-13Drug product2019-11-12
N211192-001107994902035-03-13U-3384Drug product2020-11-06
N211192-001107994902035-03-13U-2981Drug product2020-11-06
N211192-001107994902035-03-13U-2982Drug product2020-11-06
N211192-00199685952035-03-13U-2534Drug product2018-08-13
N211192-00199685952035-03-13U-3384Drug product2018-08-13
N211192-00199685952035-03-13U-2533Drug product2018-08-13
N211192-00199685952035-03-13U-2351Drug product2018-08-13
N211192-001106537102036-10-18U-33872022-06-23
N211192-001109807882039-06-07U-37432021-05-20
N211192-001109807882039-06-07U-33832021-05-20
N211192-001109807882039-06-07U-31122021-05-20
N211192-001109807882039-06-07U-31132021-05-20
N211192-001109807882039-06-07U-32142021-05-20

Orange Book exclusivity#

Application-product, Exclusivity code, Expiration table
Application-productExclusivity codeExpiration
N211192-001ODE-2422026-05-02
N211192-001I-9242026-10-24
N211192-001ODE-3682028-08-25
N211192-001ODE-4472030-10-24

openFDA label cross-check#

Cross-check layer: openFDA label JSON enriches search and identifies hydration gaps. The DailyMed Structured Product Label remains the canonical label presentation on FDA.report.

Brand, Generic, Manufacturer table
BrandGenericManufacturerSPL set IDEffective dateAvailable safety fieldsJoin
TIBSOVOIVOSIDENIBServier Pharmaceutical LLC65d254c0-67ad-42c4-b972-ad463b755b2d2025-12-22Boxed warning, Warnings, Adverse reactionsExact identifier

Boxed warning cross-check#

openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.

boxed warning

WARNING: DIFFERENTIATION SYNDROME IN AML AND MDS Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . WARNING: DIFFERENTIATION SYNDROME IN AML AND MDS See full prescribing information for complete boxed warning. Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution ( 5.1 , 6.1 ).

Warnings cross-check#

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warnings and cautions

5 WARNINGS AND PRECAUTIONS QTc Interval Prolongation : Monitor electrocardiograms and electrolytes. If QTc interval prolongation occurs, dose reduce or withhold, then resume dose or permanently discontinue TIBSOVO ( 2.3 , 5.2 ). Guillain-Barré Syndrome : Monitor patients for signs and symptoms of new motor and/or sensory findings. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome ( 2.3 , 5.3 ). 5.1 Differentiation Syndrome in AML and MDS Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome and creatinine increased. In the combination study AG120-C-009, 15% (11/71) patients with newly diagnosed AML treated with TIBSOVO plus azacitidine experienced differentiation syndrome [see Adverse Reactions (6.1) ] . Of the 11 patients with newly diagnosed AML who experienced differentiation syndrome with TIBSOVO plus azacitidine 8 (73%) recovered. Differentiation syndrome occurred as early as 3 days after start of therapy and during the first month on treatment. In the monotherapy clinical trial AG120-C-001, 25% (7/28) of patients with newly diagnosed AML and 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome [see Adverse Reactions (6.1) ] . Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis. In the monotherapy clinical trial AG120-C-001, 11% (2/19) of patients with relapsed or refractory MDS treated with TIBSOVO experienced differentiation syndrome [see Adverse Reactions (6.1) ] . Of the 2 patients who experienced differentiation syndrome, both recovered after treatment or after dose interruption of TIBSOVO. Different...

Adverse reactions cross-check#

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adverse reactions

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome in AML and MDS [see Warnings and Precautions (5.1) ] QTc Interval Prolongation [see Warnings and Precautions (5.2) ] Guillain-Barré Syndrome [see Warnings and Precautions (5.3) ] The most common adverse reactions including laboratory abnormalities (≥ 25%) in patients with AML are leukocytes decreased, diarrhea, hemoglobin decreased, platelets decreased, glucose increased, fatigue, alkaline phosphatase increased, edema, potassium decreased, nausea, vomiting, phosphate decreased, decreased appetite, sodium decreased, leukocytosis, magnesium decreased, aspartate aminotransferase increased, arthralgia, dyspnea, uric acid increased, abdominal pain, creatinine increased, mucositis, rash, electrocardiogram QT prolonged, differentiation syndrome, calcium decreased, neutrophils decreased, and myalgia ( 6.1 ). The most common adverse reactions including laboratory abnormalities (≥25%) in patients with relapsed or refractory MDS are creatinine increased, hemoglobin decrease, arthralgia, albumin decreased, aspartate aminotransferase increased, fatigue, diarrhea, cough, sodium decreased, mucositis, decreased appetite, myalgia, phosphate decreased, pruritus, and rash ( 6.1 ). The most common adverse reactions (≥15%) in patients with cholangiocarcinoma are fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash ( 6.1 ). The most common laboratory abnormalities (≥10%) in patients with cholangiocarcinoma are hemoglobin decreased, aspartate aminotransferase increased, and bilirubin increased ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Servier Pharmaceuticals at 1-800-807-6124 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. Acute Myeloid Leukemia In AML, the safety population reflects exposure to TIBSOVO at 500 mg daily in combination with azacitidine or as monotherapy in patients in Studies AG120-C-009 (N=71) and AG120-C-001 (N=213), respectively [see Clinical Studies (14.1 and 14.2...

adverse reactions table

Table 2: Adverse Reactions (≥10%) in Patients with AML Who Received TIBSOVO + azacitidine with a Difference Between Arms of ≥ 2% Compared with Placebo + azacitidine in AG120-C-009TIBSOVO + Azacitidine N=71Placebo + Azacitidine N=73Body System Adverse ReactionAll Grades n (%) Grade ≥3 n (%) All Grades n (%)Grade ≥3 n (%) Gastrointestinal disordersNausea30 (42)2 (3)28 (38)3 (4)VomitingGrouped term includes vomiting and retching.29 (41)020 (27)1 (1)InvestigationsElectrocardiogram QT prolonged14 (20)7 (10)5 (7)2 (3)Psychiatric DisordersInsomnia13 (18)1 (1)9 (12)0Blood system and lymphatic system disordersDifferentiation SyndromeDifferentiation syndrome can be associated with other commonly reported events such as peripheral edema, leukocytosis, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonia, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased.11 (15)7 (10)6 (8)6 (8)LeukocytosisGrouped term includes leukocytosis, white blood cell count increased.9 (13)01 (1)0Vascular disordersHematomaGrouped term includes hematoma, eye hematoma, catheter site hematoma, oral mucosa hematoma, spontaneous hematoma, application site hematoma, injection site hematoma, periorbital hematoma.11 (15)03 (4)0HypertensionGrouped term includes blood pressure increased, essential hypertension, and hypertension.9 (13)3 (4)6 (8)4 (5)Musculoskeletal and connective tissue disordersArthralgiaGrouped term includes pain in extremity, arthralgia, back pain, musculoskeletal stiffness, cancer pain, and neck pain.21 (30)3 (4)6 (8)1 (1)Respiratory, thoracic and mediastinal disordersDyspneaGrouped term includes dyspnea, dyspnea exertional, hypoxia, respiration failure.14 (20)2 (3)11 (15)4 (5)Nervous system disordersHeadache8 (11)02 (3)0

NDC Listings For This Application#

NDC, Name, Nonproprietary name table
NDCNameNonproprietary nameLabelerMarketing categoryStatus
71334-100TibsovoivosidenibAgios Pharmaceuticals, Inc.NDACurrent
71334-100TibsovoivosidenibAgios Pharmaceuticals, Inc.NDACurrent
71334-100TibsovoivosidenibAgios Pharmaceuticals, Inc.NDACurrent
71334-100TibsovoivosidenibAgios Pharmaceuticals, Inc.NDACurrent
71334-100TibsovoivosidenibAgios Pharmaceuticals, Inc.NDACurrent
71334-100TibsovoivosidenibAgios Pharmaceuticals, Inc.NDACurrent
71334-100TibsovoivosidenibAgios Pharmaceuticals, Inc.NDACurrent
72694-617TIBSOVOivosidenibServier Pharmaceutical LLCNDACurrent
72694-617TIBSOVOivosidenibServier Pharmaceutical LLCNDACurrent
72694-617TibsovoivosidenibServier Pharmaceuticals LLCNDACurrent

Documents#

Document, Submission type, Date table
DocumentSubmission typeDate
75946SUPPL 2023-10-25
75934SUPPL 2023-10-25
75904SUPPL 2023-10-24
71156SUPPL2022-05-26
71153SUPPL2022-05-26
71152SUPPL2022-05-26
68482SUPPL2021-08-30
68472SUPPL2021-08-26
68465SUPPL2021-08-25
66824SUPPL2021-03-22
62196SUPPL2020-03-19
58565SUPPL2019-05-06
58531SUPPL2019-05-02
55173ORIG2018-08-15
54928ORIG2018-07-20
54927ORIG2018-07-20
54926ORIG2018-07-20