Thought I'd start a new thread to discuss what was said & heard in today's call. I haven't had an opportunity to review closely, but my high-level takeaways were as follows:
Positives
* Surprised by the breadth/depth of LR-MDS ASH posters.
-- There are seven (7) imetelstat abstracts....with all seven (100%) being related to LR-MDS.
* FDA approval for LR-MDS seems quite likely at this point. Stated differently, how could they justify not granting approval?
* Timing (4-6 weeks prior to PDUFA) and likelihood (not certain) of FDA Advisory Committee review.
* IMProveMF trial has moved into the 2nd Phase.
* 50% enrollment of IMPactMF expected soon (by end 2023)
* Open to partnership/collaboration, but....
Disappointments
* Collaboration with Large Pharma (with major upfront $$$) seems unlikely (near future)
* No mention of Drs. Lane/Bruedigam's recent study.
* No ASH abstracts involving Lymphoma or IMProveMF.
* Slow enrollment rates (IMProveMF & IMPactMF)
* Investment community seems content with a "wait & see" investment approach for now.
Takeaways from today's update....
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biopearl123
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Re: Takeaways from today's update....
HI thank you for this distillation. I count 4 abstracts. One oral and three posters. It’s easy to over count with the ASH format such as it is.
Re: Takeaways from today's update....
Geron IMerge Phase 3 Presentations at Upcoming ASH Annual Meeting Reinforce Significant Durability and Breadth of Effect of Imetelstat in Lower Risk MDS
November 02, 2023
Published November 02, 2023 Business Wire
Subgroup analyses showed consistently higher transfusion independence (TI) response rates than placebo across different risk groups regardless of International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) or IPSS molecular (IPSS-M)
Robust TI rates with imetelstat treatment compared with placebo in patients with poor prognosis mutational profiles
For the nearly 20% of imetelstat-treated patients who achieved greater than 1-year sustained TI, median duration of TI was more than two years and median hemoglobin increase was more than 5 g/dL
Consistent with prior imetelstat clinical experience, the most common adverse events were thrombocytopenia and neutropenia that were manageable and of short duration
Imetelstat is currently under regulatory review by the FDA and EMA for the treatment of transfusion-dependent anemia in adult patients with lower risk MDS
FOSTER CITY, Calif.--(BUSINESS WIRE)
“The 2023 ASH abstracts present data and analyses from the IMerge Phase 3 clinical trial that reinforce the differentiated clinical profile of imetelstat in lower risk MDS, and specifically highlight that patients achieve TI irrespective of risk status based on classification systems, or specific poor prognostic mutation profiles. Of particular importance, the nearly 20% of imetelstat-treated patients who achieved one year or greater transfusion independence with accompanying hemoglobin rises of 5 g/dl and reduction of MDS-associated mutations speak to the potential of this novel therapy to provide clinical benefits to patients that have not been observed before in transfusion-dependent lower risk MDS,” said Faye Feller, M.D., Geron’s Executive Vice President, Chief Medical Officer.
“The data from IMerge Phase 3 being presented at the ASH annual meeting provides important insight into the breadth of effect of TI achieved with imetelstat across different risk subgroups and across the various underlying mutations associated with MDS, suggesting a broad use for imetelstat in patients eligible for the study, including in difficult-to-treat subgroups. Imetelstat also demonstrated efficacy among patients who were reclassified as higher risk using molecular international prognostic scoring system (IPSS-M),” said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, one of the principal investigators of IMerge Phase 3 and ASH presenter. “Additionally, our abstract showcasing a real-world data population level analysis of over 5,000 lower risk MDS patients adds to the significant literature suggesting a correlation between TI and improvement in survival. These data support the importance of TI to improve outcomes for patients with lower risk MDS.”
Abstract #194: “Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion Independence (RBC-TI) Across Different Risk Subgroups in Patients with Lower Risk Myelodysplastic Syndromes (LR MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) in IMerge Phase 3 Study”
Oral Presentation on December 9, 2023, at 2:15 p.m. PT
This abstract evaluates TI rates in patients treated with imetelstat vs. placebo across different risk subgroups as defined by International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) or IPSS molecular (IPSS-M) risk profiles and shows that patients treated with imetelstat consistently had higher TI response rates than placebo regardless of risk classification. Further, in patients re-classified as high or very high risk using IPSS-M, TI response rates with imetelstat (and not placebo) were similar to TI response rates in lower risk subgroups. This analysis suggests imetelstat has clinical activity in lower risk MDS patients independent of risk categories.
Abstract #4603: “Impact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study”
Poster Presentation on December 11, 2023, from 6-8 p.m. PT
This abstract evaluates the impact of MDS-associated mutations on clinical efficacy of imetelstat for the 165 of 178 patients for whom mutation data were available and shows that RBC-TI response rates in patients receiving imetelstat occurred regardless of the presence of baseline MDS associated mutations that have a poor prognosis (either specific mutations or multiple concurrent mutations). In patients with mutations associated with poor prognosis (TP53, ETV6, RUNX1, ASXL1, or EZH2), ≥8-week and ≥24-week, TI was observed in 31.8% and 9.1% of imetelstat-treated patients vs 0 on placebo. The 8-week TI rate for patients with 3 or more mutations was 55.6% with imetelstat compared to 14.3% with placebo. This analysis suggests clinical benefit of imetelstat across different molecularly defined subgroups and independent of the underlying molecular pattern.
Abstract #4605: “Durable Continuous Transfusion Independence (TI) With Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes (LR MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)”
Poster Presentation on December 11, 2023, from 6-8 p.m. PT
This abstract evaluates the 1-year TI responders in IMerge Phase 3, including 17.8% of imetelstat-treated patients (21/118; 95% CI, 11.4-25.9) and 1.7% of patients on placebo (1/60; 95% CI, 0-8.9). The median duration of TI for imetelstat ≥1-year TI responders was 123 weeks (95% CI, 80.4 to not evaluable); the median increase in hemoglobin during the longest TI interval was 5.18 g/dL (range, 2.67-13.76 g/dL) for the imetelstat group vs 1.67 g/dL for the placebo patient. Of the 18/21 imetelstat-treated 1-year TI responders for whom mutation data were available, 72.2% achieved ≥50% SF3B1 variant allele frequency (VAF) reduction, including 7 patients in whom there was complete elimination of MDS associated mutations. The abstract concludes that the long-term durable TI, robust increases in hemoglobin and meaningful reductions in mutational burden suggest imetelstat may have disease-modifying activity. Grade 3-4 thrombocytopenia and neutropenia occurred in 14 (67%) and 20 (95%) patients with ≥1-year TI, respectively, and the mean duration of grade 3/4 thrombocytopenia and neutropenia events was 2.25 and 1.78 weeks, respectively. 89% of grade 3/4 thrombocytopenia and 81% of grade 3/4 neutropenia was reduced to grade 1/2 within 4 weeks.
Abstract #2440: “Durable Transfusion Independence in Lower Risk Myelodysplastic Syndrome (LR MDS) Is Associated with Better Survival: A Population Level Analysis Based on a Large US Health Insurance Claims Database”
Poster Presentation on December 11, 2023, from 6-8 p.m. PT
This abstract describes a population level analysis of 5,662 lower risk MDS patients identified through Optum Clinformatics® between October 2015 and June 2022. Among these patients, 35% and 49% were transfusion-dependent before first and second lines of therapy, respectively. The median overall survival from start of second line therapy was 23.4 months overall, and 37.9 months vs 9.3 months among responders becoming transfusion independent vs non-responders, respectively (P < .0001). Despite the currently available therapies, transfusion dependence after any line of therapy is associated with poorer outcomes. Achievement of durable TI was associated with improved survival, supporting the clinical benefit of achieving transfusion independence in lower risk MDS.
These abstracts are available on the ASH 2023 Meeting website at https://www.hematology.org/meetings/ann ... /abstracts.
November 02, 2023
Published November 02, 2023 Business Wire
Subgroup analyses showed consistently higher transfusion independence (TI) response rates than placebo across different risk groups regardless of International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) or IPSS molecular (IPSS-M)
Robust TI rates with imetelstat treatment compared with placebo in patients with poor prognosis mutational profiles
For the nearly 20% of imetelstat-treated patients who achieved greater than 1-year sustained TI, median duration of TI was more than two years and median hemoglobin increase was more than 5 g/dL
Consistent with prior imetelstat clinical experience, the most common adverse events were thrombocytopenia and neutropenia that were manageable and of short duration
Imetelstat is currently under regulatory review by the FDA and EMA for the treatment of transfusion-dependent anemia in adult patients with lower risk MDS
FOSTER CITY, Calif.--(BUSINESS WIRE)
“The 2023 ASH abstracts present data and analyses from the IMerge Phase 3 clinical trial that reinforce the differentiated clinical profile of imetelstat in lower risk MDS, and specifically highlight that patients achieve TI irrespective of risk status based on classification systems, or specific poor prognostic mutation profiles. Of particular importance, the nearly 20% of imetelstat-treated patients who achieved one year or greater transfusion independence with accompanying hemoglobin rises of 5 g/dl and reduction of MDS-associated mutations speak to the potential of this novel therapy to provide clinical benefits to patients that have not been observed before in transfusion-dependent lower risk MDS,” said Faye Feller, M.D., Geron’s Executive Vice President, Chief Medical Officer.
“The data from IMerge Phase 3 being presented at the ASH annual meeting provides important insight into the breadth of effect of TI achieved with imetelstat across different risk subgroups and across the various underlying mutations associated with MDS, suggesting a broad use for imetelstat in patients eligible for the study, including in difficult-to-treat subgroups. Imetelstat also demonstrated efficacy among patients who were reclassified as higher risk using molecular international prognostic scoring system (IPSS-M),” said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, one of the principal investigators of IMerge Phase 3 and ASH presenter. “Additionally, our abstract showcasing a real-world data population level analysis of over 5,000 lower risk MDS patients adds to the significant literature suggesting a correlation between TI and improvement in survival. These data support the importance of TI to improve outcomes for patients with lower risk MDS.”
Abstract #194: “Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion Independence (RBC-TI) Across Different Risk Subgroups in Patients with Lower Risk Myelodysplastic Syndromes (LR MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) in IMerge Phase 3 Study”
Oral Presentation on December 9, 2023, at 2:15 p.m. PT
This abstract evaluates TI rates in patients treated with imetelstat vs. placebo across different risk subgroups as defined by International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) or IPSS molecular (IPSS-M) risk profiles and shows that patients treated with imetelstat consistently had higher TI response rates than placebo regardless of risk classification. Further, in patients re-classified as high or very high risk using IPSS-M, TI response rates with imetelstat (and not placebo) were similar to TI response rates in lower risk subgroups. This analysis suggests imetelstat has clinical activity in lower risk MDS patients independent of risk categories.
Abstract #4603: “Impact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study”
Poster Presentation on December 11, 2023, from 6-8 p.m. PT
This abstract evaluates the impact of MDS-associated mutations on clinical efficacy of imetelstat for the 165 of 178 patients for whom mutation data were available and shows that RBC-TI response rates in patients receiving imetelstat occurred regardless of the presence of baseline MDS associated mutations that have a poor prognosis (either specific mutations or multiple concurrent mutations). In patients with mutations associated with poor prognosis (TP53, ETV6, RUNX1, ASXL1, or EZH2), ≥8-week and ≥24-week, TI was observed in 31.8% and 9.1% of imetelstat-treated patients vs 0 on placebo. The 8-week TI rate for patients with 3 or more mutations was 55.6% with imetelstat compared to 14.3% with placebo. This analysis suggests clinical benefit of imetelstat across different molecularly defined subgroups and independent of the underlying molecular pattern.
Abstract #4605: “Durable Continuous Transfusion Independence (TI) With Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes (LR MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)”
Poster Presentation on December 11, 2023, from 6-8 p.m. PT
This abstract evaluates the 1-year TI responders in IMerge Phase 3, including 17.8% of imetelstat-treated patients (21/118; 95% CI, 11.4-25.9) and 1.7% of patients on placebo (1/60; 95% CI, 0-8.9). The median duration of TI for imetelstat ≥1-year TI responders was 123 weeks (95% CI, 80.4 to not evaluable); the median increase in hemoglobin during the longest TI interval was 5.18 g/dL (range, 2.67-13.76 g/dL) for the imetelstat group vs 1.67 g/dL for the placebo patient. Of the 18/21 imetelstat-treated 1-year TI responders for whom mutation data were available, 72.2% achieved ≥50% SF3B1 variant allele frequency (VAF) reduction, including 7 patients in whom there was complete elimination of MDS associated mutations. The abstract concludes that the long-term durable TI, robust increases in hemoglobin and meaningful reductions in mutational burden suggest imetelstat may have disease-modifying activity. Grade 3-4 thrombocytopenia and neutropenia occurred in 14 (67%) and 20 (95%) patients with ≥1-year TI, respectively, and the mean duration of grade 3/4 thrombocytopenia and neutropenia events was 2.25 and 1.78 weeks, respectively. 89% of grade 3/4 thrombocytopenia and 81% of grade 3/4 neutropenia was reduced to grade 1/2 within 4 weeks.
Abstract #2440: “Durable Transfusion Independence in Lower Risk Myelodysplastic Syndrome (LR MDS) Is Associated with Better Survival: A Population Level Analysis Based on a Large US Health Insurance Claims Database”
Poster Presentation on December 11, 2023, from 6-8 p.m. PT
This abstract describes a population level analysis of 5,662 lower risk MDS patients identified through Optum Clinformatics® between October 2015 and June 2022. Among these patients, 35% and 49% were transfusion-dependent before first and second lines of therapy, respectively. The median overall survival from start of second line therapy was 23.4 months overall, and 37.9 months vs 9.3 months among responders becoming transfusion independent vs non-responders, respectively (P < .0001). Despite the currently available therapies, transfusion dependence after any line of therapy is associated with poorer outcomes. Achievement of durable TI was associated with improved survival, supporting the clinical benefit of achieving transfusion independence in lower risk MDS.
These abstracts are available on the ASH 2023 Meeting website at https://www.hematology.org/meetings/ann ... /abstracts.