Methods for treating immune thrombocytopenia by administering (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile
Inventors
GOURLAY, Steven • Neale, Ann • NUNN, Philip • LANGRISH, Claire • Bandman, Olga • Thomas, Dolca
Assignees
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Publication Number
US-12178818-B2
Publication Date
2024-12-31
Expiration Date
Abstract
Methods for treating immune thrombocytopenia comprising administering at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (PRN1008) and pharmaceutically acceptable salts thereof are disclosed. Pharmaceutical compositions comprising at least one compound chosen from PRN1008 and pharmaceutically acceptable salts thereof are also disclosed.
Core Innovation
The invention relates to methods for achieving platelet count improvement in a human patient with immune thrombocytopenia (ITP) by administering a therapeutically effective amount of at least one specified compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof. The compound is associated with Bruton’s agammaglobulinemia tyrosine kinase (BTK) inhibition, described as reversible covalent BTK inhibition, and provides a mechanism directed to B-cell receptor (BCR) signaling and FcγR and FcεR signaling in the context of ITP.
The disclosed approach addresses the unmet need in immune thrombocytopenia (ITP), where platelet count improvement is required for patients who have very low baseline platelet counts and specific clinical characteristics. The method identifies patients as having a platelet count of less than 30,000/µL for two or more consecutive platelet counts prior to starting a treatment period, with specific timing between measurements in the 15 days prior to the treatment period.
The method defines achievement of platelet count targets, including achieving a platelet count of at least 50,000/µL. Treatment is carried out by administering the compound once a day or twice a day for a treatment period, with responder-like criteria and constraints related to consecutive platelet measurements and the proportion of platelet counts meeting the target during the treatment period. The disclosed embodiments also constrain patient selection to those with at least one characteristic chosen from a history of taking at least one prior ITP therapy prior to the start of the treatment period and/or splenectomy prior to the start of the treatment period.
Additional embodiments specify particular dosing regimens and compound forms, including pharmaceutically acceptable salts and mixture forms of (E) and (Z) isomers. Certain embodiments also specify oral administration. Overall, the disclosed subject matter combines patient identification criteria, administration frequency, and platelet-count-based success criteria to achieve defined platelet count thresholds in ITP patients.
Claims Coverage
The claims cover one inventive feature centered on a platelet-count-targeting method in ITP using a specified (R)-compound or pharmaceutically acceptable salts, administered once daily or twice daily for a treatment period, with defined patient selection based on consecutive low baseline platelet counts and at least one characteristic of prior ITP therapy and/or splenectomy, and with a defined achievement target of at least 50,000/µL.
Platelet count target achievement in ITP patients
A method for achieving a platelet count of at least 50,000/µL in a human patient with immune thrombocytopenia (ITP) in need thereof by administering a therapeutically effective amount of at least one specified compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof.
Once-daily or twice-daily dosing for a treatment period
The method comprises administering the at least one specified compound once a day or twice a day for a treatment period.
Patient selection based on consecutive very low baseline platelet counts
The human patient has been identified as having a platelet count of less than 30,000/µL for two or more consecutive platelet counts prior to the start of the treatment period, wherein two of the two or more platelet counts were measured no sooner than 7 days apart in the 15 days prior to the start of the treatment period.
Patient characteristic selection: prior ITP therapy and/or splenectomy
The human patient has been identified as having at least one characteristic chosen from a history of taking at least one prior ITP therapy prior to the start of the treatment period and splenectomy prior to the start of the treatment period.
The claims cover achieving platelet counts of at least 50,000/µL in ITP patients using the specified (R)-compound or pharmaceutically acceptable salts with once-daily or twice-daily administration, while requiring patient identification based on consecutive low baseline platelet counts and at least one of prior ITP therapy history or splenectomy.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating immune thrombocytopenia (ITP) patients identified with platelet counts of less than 30,000/µL for two or more consecutive measurements prior to treatment, including patients with a history of prior ITP therapy and/or splenectomy.
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