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Studies highlight the company's ongoing commitment to advancing care for patients with myeloid malignancies
PRINCETON, N.J., Dec. 9, 2024 /PRNewswire/ -- Taiho Oncology, Inc., presented results of two studies focused on oral therapies for patients with myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasm (MPN), at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, Dec. 7-10, 2024, in San Diego.
Findings from a Phase 1 dose escalation trial of ASTX030, an investigational combination of azacitidine and cedazuridine, were shared with attendees during an oral presentation. In addition, results of a real-world study comparing clinical outcomes with INQOVI® (decitabine and cedazuridine) tablets, an oral hypomethylating agent (HMA), versus intravenous (IV) or subcutaneous (SC) decitabine and azacitidine, respectively, were shared in a poster presentation.
Azacitidine and decitabine are HMAs. Following oral administration, HMAs are rapidly degraded by cytidine deaminase, resulting in poor oral bioavailability. Cedazuridine is a cytidine deaminase inhibitor, with the potential to increase the bioavailability of HMAs.
"We're pleased to join hematology scientific leaders at the ASH meeting to share data on oral HMAs for patients living with complications from MDS," said Harold Keer, MD, PhD, Chief Medical Officer, Taiho Oncology. "When administered at home, HMAs such as ASTX030 and INQOVI may potentially reduce the toll of time toxicity many patients with cancer experience and may help them to manage this disease long-term as a chronic condition."
Oral Presentation: Results of Phase 1 Open-Label Dose Escalation and Expansion Trial of ASTX030 (Oral Azacitidine + Cedazuridine)
This Phase 1 trial aimed to determine the optimal dose and formulation of ASTX030 to achieve oral azacitidine area under the curve (AUC) exposures comparable to SC azacitidine.
The trial enrolled 88 patients with MDS and MDS/MPN overlap syndromes, including chronic myelomonocytic leukemia (CMML), who received a median of seven cycles of treatment with ASTX030. Six combinations of azacitidine (60–144 mg) and cedazuridine (20–100 mg) doses were evaluated in the dose escalation portion of the trial, and two ASTX030 dose combinations (136 mg of azacitidine with 20 mg of cedazuridine and 144 mg of azacitidine with 20 mg of cedazuridine) were evaluated in the dose-expansion portion.
Pharmacokinetic data showed that 20 mg of cedazuridine sufficiently prevented azacitidine from degradation during first pass in the digestive tract and liver resulting in enhanced azacitidine bioavailability, achieving AUC exposures comparable to SC azacitidine, and the dose combination of 140 mg azacitidine/20 mg cedazuridine was recommended for evaluation in Phase 2.
The clinical efficacy results were consistent with parenteral azacitidine. The median overall survival was 29.5 months, with overall response rate of 56% (11% complete response, 0% partial response, 34% marrow complete response, 10% hematologic improvement), 27% stable disease, 2% progressive disease and 15% not evaluable.
Treatment emergent adverse events (TEAEs) were reported in 100% of participants, with 86% experiencing an AE of grade 3 or higher and 9% discontinuing treatment due to an AE. The most common TEAEs of grade 3 or higher were related to myelosuppression. Gastrointestinal AEs also reflected a similar safety profile to that typically associated with SC azacitidine. There was one dose-limiting toxicity that was possibly related to the study drug — a case of prolonged grade 4 neutropenia.
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"These results are promising, as they demonstrate the potential of this novel oral therapy to reduce the treatment burden for people with MDS," said Guillermo Garcia-Manero, MD, professor of Leukemia at The University of Texas MD Anderson Cancer Center and the study's lead investigator. "We look forward to soon sharing the results of a recently completed Phase 2 study of ASTX030 and are planning a Phase 3 trial of the compound."
Real-World Use Patterns and Outcomes for MDS Patients Treated with INQOVI or IV/SC HMA
The real-world study evaluated HMAs use patterns and clinical outcomes in adults with MDS who received first-line treatment with either INQOVI or a similar HMA administered subcutaneously or intravenously. Real-world treatment outcomes among MDS patients were gathered through the ConcertAI real-world electronic health records database.
Of 2,101 enrolled patients, 405 were treated with INQOVI and 1,696 with IV or SC azacitidine or decitabine.
Patients receiving INQOVI had a numerically longer median real-world overall survival (rwOS) compared to those treated with IV/SC HMA (23.2 versus 19.0 months) and lower risk of death, although the differences were not statistically significant.
Notably, median acute myeloid leukemia (AML)-free survival was 16.5 months with INQOVI versus 13.3 months with IC/SC HMAs (p=0.009). Furthermore, in a Cox-adjusted model, patients treated with INQOVI had a 16% lower risk of AML transformation or death (HR=0.84; 95% CI: 0.73–0.98; p=0.027) compared with those treated with IV or SC HMAs.
Those who received INQOVI prolonged the time to next treatment: 9.4 months, versus 7.4 months for those in the IV/SC cohort (p<0.001). Patients who received INQOVI were 18% less likely than their study counterparts receiving IV/SC HMAs to receive a next treatment (HR=0.82; 95% CI: 0.71–0.94; p=0.004).
"This real-world study is among the first and largest to examine clinical outcomes in patients treated for MDS with either first-line INQOVI or an intravenous or subcutaneous hypomethylating agent," said Tehseen Salimi, MD, MHA, Senior Vice President and Head of Medical Affairs, Taiho Oncology. "In addition to demonstrating comparable overall survival between the two treatment options, this study identified some potentially exciting unique signals of efficacy in patients who took INQOVI. These results highlight the potential value of this compound as an alternative to parenteral hypomethylating agents."
INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
Decitabine and cedazuridine, marketed under the brand name INQOVI®, is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Myelosuppression: Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.
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Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.
Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.
Embryo-Fetal Toxicity: INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment and for 6 months (females) or 3 months (males) after last dose.
ADVERSE REACTIONS
Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.
The most common adverse reactions (≥ 20%) were fatigue (55%), constipation (44%), hemorrhage (43%), myalgia (42%), mucositis (41%), arthralgia (40%), nausea (40%), dyspnea (38%), diarrhea (37%), rash (33%), dizziness (33%), febrile neutropenia (33%), edema (30%), headache (30%), cough (28%), decreased appetite (24%), upper respiratory tract infection (23%), pneumonia (21%), and transaminase increased (21%). The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased (81%), platelet count decreased (76%), neutrophil count decreased (71%), and hemoglobin decreased (55%).
USE IN SPECIFIC POPULATIONS
Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for 2 weeks after the last dose.
Renal Impairment: No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).
Please see full Prescribing Information.
About Taiho Oncology, Inc.
The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small molecule clinical candidates targeting solid tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company's European and Canadian operations, which are located in Baar, Switzerland and Oakville, Ontario, Canada.
For more information, visit https://www.taihooncology.com/, and follow us on LinkedIn and X.
Taiho Oncology and the Taiho Oncology logo are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries.
Taiho Oncology Contact:
Leigh Labrie
(609) 664-9878
[email protected]
SOURCE Taiho Oncology
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PRINCETON, N.J., Dec. 9, 2024 /PRNewswire/ -- Taiho Oncology, Inc., presented results of two studies focused on oral therapies for patients with myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasm (MPN), at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, Dec. 7-10, 2024, in San Diego.
Findings from a Phase 1 dose escalation trial of ASTX030, an investigational combination of azacitidine and cedazuridine, were shared with attendees during an oral presentation. In addition, results of a real-world study comparing clinical outcomes with INQOVI® (decitabine and cedazuridine) tablets, an oral hypomethylating agent (HMA), versus intravenous (IV) or subcutaneous (SC) decitabine and azacitidine, respectively, were shared in a poster presentation.
Azacitidine and decitabine are HMAs. Following oral administration, HMAs are rapidly degraded by cytidine deaminase, resulting in poor oral bioavailability. Cedazuridine is a cytidine deaminase inhibitor, with the potential to increase the bioavailability of HMAs.
"We're pleased to join hematology scientific leaders at the ASH meeting to share data on oral HMAs for patients living with complications from MDS," said Harold Keer, MD, PhD, Chief Medical Officer, Taiho Oncology. "When administered at home, HMAs such as ASTX030 and INQOVI may potentially reduce the toll of time toxicity many patients with cancer experience and may help them to manage this disease long-term as a chronic condition."
Oral Presentation: Results of Phase 1 Open-Label Dose Escalation and Expansion Trial of ASTX030 (Oral Azacitidine + Cedazuridine)
This Phase 1 trial aimed to determine the optimal dose and formulation of ASTX030 to achieve oral azacitidine area under the curve (AUC) exposures comparable to SC azacitidine.
The trial enrolled 88 patients with MDS and MDS/MPN overlap syndromes, including chronic myelomonocytic leukemia (CMML), who received a median of seven cycles of treatment with ASTX030. Six combinations of azacitidine (60–144 mg) and cedazuridine (20–100 mg) doses were evaluated in the dose escalation portion of the trial, and two ASTX030 dose combinations (136 mg of azacitidine with 20 mg of cedazuridine and 144 mg of azacitidine with 20 mg of cedazuridine) were evaluated in the dose-expansion portion.
Pharmacokinetic data showed that 20 mg of cedazuridine sufficiently prevented azacitidine from degradation during first pass in the digestive tract and liver resulting in enhanced azacitidine bioavailability, achieving AUC exposures comparable to SC azacitidine, and the dose combination of 140 mg azacitidine/20 mg cedazuridine was recommended for evaluation in Phase 2.
The clinical efficacy results were consistent with parenteral azacitidine. The median overall survival was 29.5 months, with overall response rate of 56% (11% complete response, 0% partial response, 34% marrow complete response, 10% hematologic improvement), 27% stable disease, 2% progressive disease and 15% not evaluable.
Treatment emergent adverse events (TEAEs) were reported in 100% of participants, with 86% experiencing an AE of grade 3 or higher and 9% discontinuing treatment due to an AE. The most common TEAEs of grade 3 or higher were related to myelosuppression. Gastrointestinal AEs also reflected a similar safety profile to that typically associated with SC azacitidine. There was one dose-limiting toxicity that was possibly related to the study drug — a case of prolonged grade 4 neutropenia.
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"These results are promising, as they demonstrate the potential of this novel oral therapy to reduce the treatment burden for people with MDS," said Guillermo Garcia-Manero, MD, professor of Leukemia at The University of Texas MD Anderson Cancer Center and the study's lead investigator. "We look forward to soon sharing the results of a recently completed Phase 2 study of ASTX030 and are planning a Phase 3 trial of the compound."
Real-World Use Patterns and Outcomes for MDS Patients Treated with INQOVI or IV/SC HMA
The real-world study evaluated HMAs use patterns and clinical outcomes in adults with MDS who received first-line treatment with either INQOVI or a similar HMA administered subcutaneously or intravenously. Real-world treatment outcomes among MDS patients were gathered through the ConcertAI real-world electronic health records database.
Of 2,101 enrolled patients, 405 were treated with INQOVI and 1,696 with IV or SC azacitidine or decitabine.
Patients receiving INQOVI had a numerically longer median real-world overall survival (rwOS) compared to those treated with IV/SC HMA (23.2 versus 19.0 months) and lower risk of death, although the differences were not statistically significant.
Notably, median acute myeloid leukemia (AML)-free survival was 16.5 months with INQOVI versus 13.3 months with IC/SC HMAs (p=0.009). Furthermore, in a Cox-adjusted model, patients treated with INQOVI had a 16% lower risk of AML transformation or death (HR=0.84; 95% CI: 0.73–0.98; p=0.027) compared with those treated with IV or SC HMAs.
Those who received INQOVI prolonged the time to next treatment: 9.4 months, versus 7.4 months for those in the IV/SC cohort (p<0.001). Patients who received INQOVI were 18% less likely than their study counterparts receiving IV/SC HMAs to receive a next treatment (HR=0.82; 95% CI: 0.71–0.94; p=0.004).
"This real-world study is among the first and largest to examine clinical outcomes in patients treated for MDS with either first-line INQOVI or an intravenous or subcutaneous hypomethylating agent," said Tehseen Salimi, MD, MHA, Senior Vice President and Head of Medical Affairs, Taiho Oncology. "In addition to demonstrating comparable overall survival between the two treatment options, this study identified some potentially exciting unique signals of efficacy in patients who took INQOVI. These results highlight the potential value of this compound as an alternative to parenteral hypomethylating agents."
INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
Decitabine and cedazuridine, marketed under the brand name INQOVI®, is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Myelosuppression: Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.
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Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.
Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.
Embryo-Fetal Toxicity: INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment and for 6 months (females) or 3 months (males) after last dose.
ADVERSE REACTIONS
Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.
The most common adverse reactions (≥ 20%) were fatigue (55%), constipation (44%), hemorrhage (43%), myalgia (42%), mucositis (41%), arthralgia (40%), nausea (40%), dyspnea (38%), diarrhea (37%), rash (33%), dizziness (33%), febrile neutropenia (33%), edema (30%), headache (30%), cough (28%), decreased appetite (24%), upper respiratory tract infection (23%), pneumonia (21%), and transaminase increased (21%). The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased (81%), platelet count decreased (76%), neutrophil count decreased (71%), and hemoglobin decreased (55%).
USE IN SPECIFIC POPULATIONS
Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for 2 weeks after the last dose.
Renal Impairment: No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).
Please see full Prescribing Information.
About Taiho Oncology, Inc.
The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small molecule clinical candidates targeting solid tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company's European and Canadian operations, which are located in Baar, Switzerland and Oakville, Ontario, Canada.
For more information, visit https://www.taihooncology.com/, and follow us on LinkedIn and X.
Taiho Oncology and the Taiho Oncology logo are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries.
Taiho Oncology Contact:
Leigh Labrie
(609) 664-9878
[email protected]
SOURCE Taiho Oncology
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