Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Platelet count-agnostic methods of treating myelofibrosis

A technology for bone marrow fibrosis and platelet count, which can be used in pharmaceutical formulations, medical preparations containing active ingredients, antitumor drugs, etc., and can solve problems such as dose reduction

Pending Publication Date: 2021-06-22
SIERRA ONCOLOGY INC
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Unfortunately, the recently approved JAK2 / FLT3 inhibitor, fedratinib, has similar hematological toxicity to ruxolitinib and is only administered when the baseline platelet count is 50x10 9 For patients with grade 4 thrombocytopenia or other symptomatic adverse events, reduce dose in patients with / L or higher
Therefore, despite the availability of ruxolitinib and filzotinib, additional therapies for this deadly disease are needed

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Platelet count-agnostic methods of treating myelofibrosis
  • Platelet count-agnostic methods of treating myelofibrosis
  • Platelet count-agnostic methods of treating myelofibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0185] Example 1: SIMPLIFY-1 and SIMPLIFY-2

[0186] Mometinib (MMB) is a potent, selective, orally bioavailable small molecule inhibitor of JAK1, JAK2, and ACVR1 developed for the treatment of myelofibrosis (MF). However, in two phase III clinical trials (SIMPLIFY-1 and -2) in first-line and second-line treatment of MF, MMB was unable to meet both the predefined secondary endpoint of TSS response in SIMPLIFY-1 and the primary of SRR in SIMPLIFY-2 end.

[0187] In the SIMPLIFY-1 trial (NCT01969838), the effect of MMB and ruxolitinib (RUX) on JAK inhibitor-naïve patients with a platelet count ≥50x 10 9 / L in patients with myelofibrosis. Patients (N=432) with high-risk or intermediate-2 risk or symptomatic intermediate-1 risk myelofibrosis received 24 weeks of 200 mg MMB once daily or RUX 20 mg twice daily (or per label), All patients thereafter could receive open-label mometinib. Efficacy was measured with the aim of demonstrating the non-inferiority of MMB to RUX by sple...

Embodiment 2

[0193] Example 2: SIMPLIFY-1 and SIMPLIFY-2 Reanalysis

[0194] We reanalyzed data from the SIMPLIFY-1 and SIMPLIFY-2 trials and found mometinib was effective at platelet counts of 150x10 9 Effective in reducing spleen size (SSR), improving Total Symptom Score (TSS), and improving infusion-independence rates in patients with / L or less, without mometinib administration causing thrombocytopenia and thus requiring no intervention for thrombocytopenia Reduce or interrupt dose. Our reanalysis showed that MMB was effective in JAKi-naïve patients and as second-line therapy for RUX, providing reduced risk of thrombocytopenia in patients with or at risk of thrombocytopenia from underlying disease and current standard of care. Benefits of splenomegaly, improvement of symptoms associated with myelofibrosis, and increased rates of infusion independence.

[0195] Platelet levels during MMB or RUX treatment

[0196] Figure 31 Shown is a graph of mean (± standard error) platelet co...

Embodiment 3

[0261] Kinetic and time-to-event analyzes demonstrated that for mometinib-treated patients who did not receive Janus kinase inhibitors of patients with myelofibrosis, significantly reduced blood transfusion requirements compared with ruxolitinib head-to-head

[0262] Mometinib (MMB) is a potent, selective, orally bioavailable small molecule inhibitor of JAK1, JAK2, and ACVR1 developed for the treatment of intermediate- and high-risk myelofibrosis (MF). Systemic inflammation, integral to the pathogenesis of MF, results in increased ACVR1 activity, which in turn increases hepcidin secretion, leading to disturbances in iron homeostasis and iron-limiting anemia (Ganz T. "Systemic Iron Homeostasis:, Physiol Rev. 2013; 93:1721–41; and Langdon JM, Yates SC, Femnou LK et al. “Hepcidin-dependent and hepcidin-independent regulation of erythropoiesis in a mouse model of anemia of chronic inflammation”, Am J Hematol. 2014;89:470–9). Inhibition of ACVR1 by MMB is unique within the JAK ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Dilution degreeaaaaaaaaaa
Login to View More

Abstract

Reanalysis of the SIMPLIFY 1 and 2 trials data indicates MMB is effective in JAKi-naive patients and in second line therapy to RUX, providing benefits of reducing enlarged spleens, improving myelofibrosis-related symptoms, and increasing transfusion independence in patient at risk for thrombocytopenia from the underlying disease and RUX therapy. Accordingly, methods of treating myeloproliferative neoplasms (MPN) such as myelofibrosis are described. The methods can include administering a therapeutically effective amount of momelotinib or a pharmaceutically acceptable salt thereof to a subject identified as having (i) myelofibrosis and (ii) a platelet count of less than 150 * l09 / L. Also described are methods including administering to a subject with myelofibrosis a therapeutically effective stable dose of momelotinib or a pharmaceutically acceptable salt thereof, for a period of a plurality of weeks, where the subject is assessed as maintaining a platelet count above a predetermined threshold platelet count during the period.

Description

[0001] cross reference [0002] This application claims the benefit of U.S. Provisional Application 62 / 720,782, filed August 21, 2018, U.S. Provisional Application 62 / 749,052, filed October 22, 2018, and U.S. Provisional Application 62 / 774,752, filed December 3, 2018 , each of which is incorporated herein by reference in its entirety. Background technique [0003] Myelofibrosis (MF) is a disease that affects approximately 40,000 to 50,000 patients worldwide, of which 70-80% are classified as intermediate to high risk MF patients. The median survival of all MF patients was approximately 6 years, but those classified as intermediate-2 or high-risk MF had a significantly worse median survival of 4 years and 2.25 years, respectively. [0004] Myelofibrosis can arise de novo as primary MF (PMF), or it can arise from a pre-existing myeloproliferative neoplasm (MPN), primarily polycythemia vera (PV) or essential thrombocythemia (ET). Once these conditions reach the overt fibrotic s...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/444A61K31/505A61K31/5377
CPCA61K31/5377A61K31/519A61P35/00A61K2300/00A61K9/0053
Inventor B·J·克伦克G·D·史密斯R·M·J·多纳休
Owner SIERRA ONCOLOGY INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com