Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication AGRYLIN is indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative neoplasms, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events. FDA label
Also known as anagrelide hydrochloride, SPD422
Anagrelide · 3 trials · 2 indications
A response was defined as platelet counts to \<600x10\^9/L across consecutive visits for at least 4 weeks following at least 3 months of treatment.
Baseline considered from study SPD422-308 (NCT01214915). Final assessment was defined as the last non-missing data (End of study visit in SPD422-309 \[NCT01467661\], or early termination visit either in SPD422-308 \[NCT01214915\] or SPD422-309 \[NCT01467661\], or last available study visit).
Baseline considered from study SPD422-308 (NCT01214915). Final assessment was defined as the last non-missing data (End of study visit in SPD422-309 \[NCT01467661\], or early termination visit either in SPD422-308 \[NCT01214915\] or SPD422-309 \[NCT01467661\], or last available study visit).
Baseline considered from study SPD422-308 (NCT01214915). Final assessment was defined as the last non-missing data (End of study visit in SPD422-309 \[NCT01467661\], or early termination visit either in SPD422-308 \[NCT01214915\] or SPD422-309 \[NCT01467661\], or last available study visit). Participants who achieved platelet count \<600 x 10\^9 platelets per liter at each visit were reported.
Baseline considered from study SPD422-308 (NCT01214915). Final assessment was defined as the last non-missing data (End of study visit in SPD422-309 \[NCT01467661\], or early termination visit either in SPD422-308 \[NCT01214915\] or SPD422-309 \[NCT01467661\], or last available study visit). Participants who achieved platelet count \<600 x 10\^9 platelets per liter during the post-marketing trial were reported.
Baseline considered from study SPD422-308 (NCT01214915). Final assessment (FA) was defined as the last nonmissing data (End of study visit in SPD422-309 \[NCT01467661\], or early termination visit either in SPD422-308 \[NCT01214915\] or SPD422-309 \[NCT01467661\], or last available study visit). Participants who had platelet count \<600 x 10\^9 platelet per liter and greater than equal (\>=) 600 x 10\^9 platelet per liter at the final assessment as a shift from baseline was reported. Percentage of participants with shift = number of participants with shift / Safety analysis set (53 participants) \* 100.
Baseline considered from study SPD422-308 (NCT01214915). Final assessment (FA) was defined as the last non-missing data (End of study visit in SPD422-309 \[NCT01467661\], or early termination visit either in SPD422-308 \[NCT01214915\] or SPD422-309 \[NCT01467661\], or last available study visit). Participants who had platelet count \<600 x 10\^9 platelet per liter and greater than equal (\>=) 600 x 10\^9 platelet per liter at the final assessment as a shift from baseline during the post marketing trial was reported. Percentage of participants with shift = number of participants with shift / post-marketing safety analysis set (33 participants) \* 100.
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. Clinical Laboratory analysis included hematology, biochemistry, and urinalysis.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. Clinical Laboratory analysis included hematology, biochemistry, and urinalysis.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. Vital signs included pulse rate, systolic and diastolic blood pressure, and weight.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. Vital signs included pulse rate, systolic and diastolic blood pressure, and weight.
Standard 12-Lead ECG analysis was performed to identify the ECG abnormalities. Clinically significant abnormalities like QT prolongation, atrial fibrillation, were decided by the investigator during the study.
An active metabolite has therapeutic activity similar to the parent compound and must be considered in therapeutic pharmacokinetics.
| Arm | Type | Description |
|---|---|---|
| Anagrelide Hydrochloride | EXPERIMENTAL | - |
| SPD422 (anagrelide hydrochloride) | EXPERIMENTAL | - |
| Younger Participants (18-50 years) | EXPERIMENTAL | - |
| Elderly Participants (≥65 years) | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Anagrelide Hydrochloride | DRUG | Subjects will be started at 1.0 mg per day and titrated as necessary. |
| SPD422 (anagrelide hydrochloride) | DRUG | Subjects will be continued on the dose of anagrelide that controlled their platelet levels in Study 308 and titrated if necessary. |
Inclusion Criteria: * Subjects must have previously been treated with a cytoreductive therapy and been intolerant or refractory to that therapy. Exclusion Criteria: * Subjects should not have any other underlying conditions or medications that would confound the study analysis or interact with th...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE3 | Bomedemstat |
| Incyte Corporation | INCY | 2 | PHASE3 | INCA033989, INCB057643, Ruxolitinib |
Anagrelide is used to lower elevated platelet counts in adults with essential thrombocythemia (ET), a myeloproliferative blood disorder in which the bone marrow produces too many platelets. Treatment is directed at patients at risk of thrombotic or bleeding complications from a high platelet count. It is given as an oral small molecule therapy.
Anagrelide is a PDE3A and PDE3B inhibitor. By inhibiting these phosphodiesterases, it interferes with megakaryocyte maturation and platelet production, reducing the number of circulating platelets. This mechanism distinguishes it from cytoreductive agents that act on cell division more broadly, and it is the basis for its platelet-lowering effect in essential thrombocythemia.
Anagrelide is developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. Takeda has sponsored clinical studies of the drug in essential thrombocythemia, including pharmacokinetic work in elderly and younger patients and a platelet-lowering study in Japanese adults with at-risk ET.
Anagrelide is in Phase 2 development for essential thrombocythemia. One completed trial is recorded at Phase 2, and a separate completed study in Japanese adults with at-risk ET was conducted at Phase 3. No active trials are currently listed, so the program is not in an ongoing clinical stage at this time.
Anagrelide has been studied in completed trials including NCT01214915, a Phase 3 study of SPD422 on platelet lowering and safety in Japanese adults with at-risk essential thrombocythemia, and NCT00413634, a Phase 2 pharmacokinetic study in elderly and young patients with ET conducted in Spain, Sweden, and the United Kingdom.
Yes. Anagrelide hydrochloride is the salt form of anagrelide and refers to the same active substance. Other names used for this agent include anagrelide 0.5 mg, reflecting a common dosage strength, and Anagrelide Hydrochloride. All of these names describe the same PDE3A and PDE3B inhibitor used in essential thrombocythemia.