On June 12, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported new data and analyses from IMerge Phase 3 reporting robust durability of transfusion independence (TI), evidence for disease-modifying activity and favorable fatigue patient-reported outcomes (PRO) in lower risk myelodysplastic syndromes (MDS) patients treated with the Company’s first-in-class telomerase inhibitor, imetelstat, vs. placebo (Press release, Geron, JUN 12, 2023, View Source [SID1234632657]). The data and analyses were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting, which took place from June 8-11, 2023 in Frankfurt, Germany and virtually.

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"The new IMerge Phase 3 data and analyses presented at EHA (Free EHA Whitepaper) continue to support the unprecedented and differentiating attributes of imetelstat, including 24-week transfusion independence across key MDS subgroups, potential disease-modifying activity, as well as favorable patient-reported outcomes (PRO) data on meaningful improvement in fatigue," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "Each of these qualities address important unmet needs for lower risk MDS patients due to the limitation of current treatment options. Submission of our New Drug Application later this month is a significant step to hopefully bring imetelstat to these transfusion burdened patients."

Presentation Title: Continuous Transfusion Independence with Imetelstat in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3

Top-line results from the primary analysis of IMerge Phase 3 presented earlier this month at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) (ASCO) (Free ASCO Whitepaper) Annual Meeting were also covered in the EHA (Free EHA Whitepaper) presentation, including the primary endpoint of 8-week transfusion independence (TI) and key secondary endpoint of 24-week TI were met with high statistical significance (P<0.001) for imetelstat-treated patients vs. placebo. Further, mean hemoglobin levels in imetelstat-treated patients increased significantly (P<0.001) over time compared to placebo patients.

In addition to these results, the EHA (Free EHA Whitepaper) presentation also provided new data and analyses highlighting clinically meaningful and durable TI for imetelstat-treated patients vs. placebo. As of a January 2023 data cut-off, 17.8% (21/118) of imetelstat-treated patients vs. 1.7% (1/60) of placebo-treated patients achieved 1-year TI (P=0.002), representing 63.6% of 24-week TI imetelstat responders.

Two new analyses presented at EHA (Free EHA Whitepaper) on TI responses by subgroups underscored the breadth of potential effect of imetelstat vs. placebo. The first analysis reported higher durability of TI for imetelstat-treated patients vs. placebo across key MDS subgroups:

Durability of RBC-TI for 8-Week TI Responders Across Key LR MDS Subgroups

Imetelstat
median, weeks (95% CI)

Placebo
median, weeks (95% CI)

Hazard ratio
(95% CI)

P-value

Overall

51.6 (26.9–83.9)

13.3 (8.0–24.9)

0.23 (0.09–0.57)

<0.001

WHO category

RS+

46.9 (25.9–83.9)

16.9 (8.0–24.9)

0.32 (0.11–0.95)

0.035

RS-

51.6 (11.9–NE)

11.2 (10.1–NE)

0.11 (0.01–1.43)

0.062

Prior RBC transfusion burden per IWG 2006

4–6 units/8 weeks

51.9 (24.9–122.9)

16.9 (10.1–24.9)

0.35 (0.13–0.96)

0.035

6 units/8 weeks

39.9 (15.9–NE)

8.4 (8.0–NE)

0.04 (0.003–0.48)

<0.001

IPSS risk category

Low

43.9 (25.0–NE)

15.1 (8.0–24.9)

0.26 (0.10–0.68)

0.004

Intermediate-1

51.6 (11.9–NE)

10.1 (NE–NE)

0.15 (0.01–2.47)

0.128

Baseline sEPO

≤500 mU/mL

51.6 (26.9–83.9)

13.3 (8.0–24.9)

0.21 (0.075–0.61)

0.002

>500 mU/mL

122.9 (8.14–NE)

14.6 (12.3–NE)

0.34 (0.03–3.85)

0.364

Prior ESA use

Yes

43.9 (26.9–80.0)

13.3 (8.0–24.9)

0.26 (0.10–0.72)

0.006

No

122.9 (8.14–NE)

14.6 (12.3–NE)

0.34 (0.03–3.85)

0.364

____________________
Data cut-off: October 13, 2022.

Hazard ratio (95% CI) from the Cox proportional hazard model, stratified by prior RBC transfusion burden (≥4 to ≤6 vs >6 RBC units/8 weeks during a 16-week period prior to randomization) and baseline IPSS risk category (low vs intermediate-1), with treatment as the only covariate. P-value (2-sided) for superiority of imetelstat vs placebo in hazard ratio based on stratified log-rank test.
ESA, erythropoiesis-stimulating agent; IPSS, International Prognostic Scoring System; IWG, International Working Group; LR-MDS, lower-risk myelodysplastic syndromes; NE, not estimable; RBC, red blood cell; RS, ring sideroblast; sEPO, serum erythropoietin; TI, transfusion independence.

The second analysis reported higher 24-week TI for imetelstat-treated patients vs. placebo across key MDS subgroups:

Comparable 24-Week RBC-TI Rate Across Key LR MDS Subgroups

Imetelstat
n/N (%)

Placebo,
n/N (%)

% Difference

(95% CI)

P-value

Overall

33/118 (28.0)

2/60 (3.3)

24.6 (12.64–34.18)

<0.001

WHO category

RS+

24/73 (32.9)

2/37 (5.4)

20.5 (−0.03–35.75)

0.003

RS-

9/44 (20.5)

0/23 (0.0)

0.11 (0.01–1.43)

0.019

Prior RBC transfusion burden per IWG 2006

4–6 units/8 weeks

19/62 (30.6)

2/33 (6.1)

24.6 (5.68–38.66)

0.006

6 units/8 weeks

39.9 (15.9–NE)

8.4 (8.0–NE)

0.04 (0.003–0.48)

<0.001

IPSS risk category

Low

23/80 (28.8)

2/39 (5.1)

23.6 (7.23–35.75)

0.003

Intermediate-1

10/38 (26.3)

0/21 (0)

26.3 (3.46–43.39)

0.009

Baseline sEPO

≤500 mU/mL

29/87 (33.3)

2/36 (5.6)

27.8 (10.46–39.71)

0.002

>500 mU/mL

4/26 (15.4)

0/22 (0)

15.4 (−5.81–35.73)

0.050

Prior ESA use

Yes

31/108 (28.7)

2/52 (3.8)

24.9 (11.61–35.00)

<0.001

No

2/10 (20)

0/8

20.0 (-23.47–55.78)

0.225

_____________
Data cut-off: October 13, 2022.

95% CI based on Wilson Score method. P-value determined by the Cochran-Mantel-Haenszel test, with stratification for prior RBC transfusion burden (≥4 to ≤6 vs >6 RBC units/8 weeks during a 16-week period prior to randomization) and baseline IPSS risk category (low vs intermediate-1) applied to randomization.

ESA, erythropoiesis-stimulating agent; IPSS, International Prognostic Scoring System; IWG, International Working Group; LR-MDS, lower-risk myelodysplastic syndromes; RBC, red blood cell; RS, ring sideroblast; sEPO, serum erythropoietin; TI, transfusion independence.

Additionally, the rate of 24-week TI was higher with imetelstat vs. placebo regardless of baseline mutation status, telomerase activity (TA), telomerase length (TL), and human telomerase reverse transcriptase (hTERT).

"For the first time at EHA (Free EHA Whitepaper), we see comparable 24-week TI across key MDS subgroups, which is especially meaningful for patients without ring sideroblasts (RS-) and very heavily transfusion burdened patients, who particularly have limited options today," said Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany, who presented the data at EHA (Free EHA Whitepaper) and is an IMerge investigator. "In addition to the durability of TI, imetelstat-treated patients also achieved significant increases in hemoglobin and reductions of transfusion units that could be life changing for lower risk MDS patients, who often present with symptomatic anemia and transfusion dependence."

As previously reported, the safety profile observed with imetelstat in IMerge Phase 3 was consistent with prior clinical experience with no new safety signals. The EHA (Free EHA Whitepaper) presentation provided new data on the consequences of the grade 3-4 thrombocytopenia and neutropenia which were most often reported during Cycles 1-3 and led to dose modifications. While approximately 50% of patients treated with imetelstat had dose reductions due to treatment emergent adverse events (TEAE), less than 15% of patients discontinued treatment due to TEAE. Discontinuation of imetelstat treatment in these patients due to a TEAE generally occurred late in treatment, with a median time to treatment discontinuation of 21.1 weeks (range 2.3 to 44.0 weeks).

Presentation Title: Disease-Modifying Activity of Imetelstat in Patients with Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3

"In IMerge Phase 3, not only did we observe efficacy with imetelstat across the spectrum of genetic mutations associated with lower risk MDS, but we also saw a reduction in mutation burden, as measured by variant allele frequency (VAF). Furthermore, greater reduction of VAF in multiple genes correlated with the clinical endpoints of TI response, longer TI duration and increase in hemoglobin levels, suggesting the potential of imetelstat to modify the disease. This is the first therapy we know of that may alter the underlying biology of lower risk MDS by potentially reducing or eliminating malignant clones and improving ineffective erythropoiesis," said Valeria Santini, M.D., MDS Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy, who presented the data at EHA (Free EHA Whitepaper) and is an IMerge investigator.

In the EHA (Free EHA Whitepaper) presentation, new data on cytogenetic responses and reductions in bone marrow RS supported the telomerase inhibition mechanism of action (MOA) of imetelstat. Among patients with cytogenetic abnormalities at baseline, the cytogenetic response rate was 35% (9/26) in imetelstat-treated patients and 15% (2/13) in the placebo group. Among cytogenetic responders, 89% (8/9) of patients in the imetelstat group and 50% (1/2) in the placebo group also achieved 8-week TI. A higher percentage of patients treated with imetelstat (40.8%) vs. placebo (9.7%) had a ≥50% reduction in central bone marrow RS. TI responses were enriched in patients achieving a ≥50% reduction in central bone marrow RS.

Furthermore, the EHA (Free EHA Whitepaper) presentation provided updated data on VAF reductions and new analyses on the correlation of such reductions with clinical responses which further support the potential disease-modifying activity of imetelstat. Reductions in variant allele frequency (VAF) of genes frequently mutated in MDS were greater for imetelstat-treated patients than placebo: SF3B1 (P< 0.001), TET2 (P= 0.032), DNMT3A (P= 0.019) and ASXL1 (P= 0.146). More patients treated with imetelstat vs. placebo had ≥50% VAF reduction in these mutations.

For patients with the SF3B1 mutation, 29.5% (23/78) of those treated with imetelstat vs. 2.6% (1/38) on placebo (P=0.001) had a ≥50% VAF reduction. Imetelstat treatment resulted in sustained reduction of SF3B1VAF over time. In the imetelstat group, 83% (19/23) of patients had 8-week TI among patients who achieved ≥50% maximum reduction from baseline inSF3B1 VAF vs. 38% (21/55) of those who did not.

Similarly, TI responders were also enriched in imetelstat-treated patients achieving ≥50% reduction in TET2 VAF. In the imetelstat group, 83% (10/12) of patients had 8-week RBC-TI among patients who achieved ≥50% maximum reduction from baseline in TET2 VAF vs 43% (10/23) of those who did not.

In imetelstat-treated patients, 24-week and 1-year TI responders were enriched in patients achieving ≥50% reduction in SF3B1andTET2VAF. VAF reduction in SF3B1, TET2and DNMT3Acorrelated with longer TI duration and increases in hemoglobin levels in imetelstat-treated patients. Further, 8-week and 24-week TI correlated with reduction in RS+ cells, cytogenetic responses and VAF reduction. These correlations suggest the disease-modifying activity of imetelstat.

Presentation Title: Analysis of Patient-Reported Fatigue in IMerge Phase 3 Trial of Imetelstat vs. Placebo in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents (ESA)

"The patient-reported outcome data from IMerge Phase 3 is particularly important as fatigue is a concern for lower risk MDS patients, most of whom are elderly. Furthermore, many of the current treatments for these patients cause fatigue. It is therefore very welcome news that imetelstat-treated patients showed sustained meaningful improvement in patient-reported fatigue vs. placebo. This is the first Phase 3 trial we know of to show an improvement in fatigue in lower risk MDS patients," stated Dr. Platzbecker.

The EHA (Free EHA Whitepaper) presentation described results from an exploratory analysis from IMerge Phase 3 of patient-reported fatigue conducted using Functional Assessment of Chronic Illness Therapy, or FACIT, a validated 13-item patient questionnaire. The analysis reported imetelstat-treated patients were more likely to have sustained meaningful improvement in fatigue, as well as experience such improvement more quickly.

Patients treated with imetelstat reported a lower rate of sustained meaningful deterioration in fatigue than placebo (43.2% vs 45.6%), while also receiving fewer transfusion units over time. For patients treated with imetelstat, there was a numerically higher percentage of patients reporting any episode of sustained meaningful improvement in fatigue. Further, patients receiving imetelstat experienced a shorter median time to first sustained clinically meaningful improvement in fatigue vs placebo (28.3 vs 65.0 weeks).

For patients treated with imetelstat, there were significant associations between sustained meaningful improvement in fatigue and 8- and 24-week TI and HI-E response rates, an association not seen in the placebo group.

Additional analysis showed that patients experiencing grade 3 or 4 neutropenia or thrombocytopenia had the same rates of sustained meaningful improvement in fatigue (52.5% and 53.4%, respectively) as the total imetelstat population (50%).

Additional Presentations at EHA (Free EHA Whitepaper)

In addition to these IMerge Phase 3 presentations, Geron collaborators presented a translational analysis from a subset of IMerge Phase 2 patients, as well as imetelstat myelofibrosis (MF) pre-clinical results.

The presentation slides and posters are available on the Publications section of Geron’s website: View Source

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Geron plans to submit a New Drug Application (NDA) in the U.S. in June 2023 and a Marketing Authorization Application (MAA) in the EU in the second half of 2023 in the lower risk MDS indication.

On June 12, 2023 Day One biopharmaceuticals presented its corporate presentation (Presentation, Day One, JUN 12, 2023, View Source [SID1234632654]).

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On June 12, 2023 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that positive results from the global phase III COMMODORE 1 and 2 studies, evaluating the efficacy and safety of crovalimab, an investigational, novel anti-C5 recycling monoclonal antibody, compared to eculizumab, one of the current standard of care in paroxysmal nocturnal hemoglobinuria (PNH) were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress, taking place in Frankfurt, Germany on 8-11 June 2023 (Press release, Chugai, JUN 12, 2023, View Source [SID1234632652]).

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"Crovalimab, which is administered subcutaneously every four weeks, is expected to decrease the treatment burden of patients with PNH, possibly reducing dosing time and bringing the option of self-administration at home," said Chugai’s President and CEO, Dr. Osamu Okuda. "We will continue to work with Roche towards global filing for this drug so that the benefits of crovalimab can be delivered as soon as possible to patients and caregivers who are waiting for this new treatment."

PNH is a rare and life-threatening blood condition in which red blood cells are destroyed by the complement system – part of the innate immune system – causing symptoms such as anemia, fatigue, blood clots, and kidney disease.1 C5 inhibitors are known to be effective in treating the condition.2 Chugai’s Recycling Antibody technology has been applied to crovalimab and re-engineered to be recycled within the bloodstream, enabling sustained complement inhibition through low-dose subcutaneous administration every four weeks.3,4

In the COMMODORE 2 study, 79.3% (95% CI: 72.9, 84.5) of participants treated with crovalimab achieved hemolysis control from week five to week 25 compared with 79.0% (95% CI: 69.7, 86.0) with eculizumab. Additionally, 65.7% (95% CI: 56.9, 73.5) achieved transfusion avoidance (TA) from baseline to week 25 with crovalimab and 68.1% (95% CI: 55.7, 78.5) with eculizumab. TA is defined as people who become concentrated red blood cell transfusion-free and do not require transfusion per protocol-specified guidelines. Blood transfusion requirements are important clinical measures of hemolysis caused by complement dysregulation in PNH. A clinically meaningful improvement in FACIT-Fatigue score (improvement of over 5 points), which is a patient-reported scale to measure fatigue, from baseline to week 25 occurred in both arms, with an adjusted mean change of 7.8 (95% Cl: 6.5, 9.1) with crovalimab, and 5.2 (95% Cl: 3.4, 6.9) with eculizumab.5

Adverse events (AEs) occurred in 78% of participants treated with crovalimab and 80% treated with eculizumab in the COMMODORE 2 study. Serious infections occurred in 3% of participants treated with crovalimab and 7% with eculizumab, with no meningococcal infections. The most common AE that occurred in 16% of people treated with crovalimab and 13% of those treated with eculizumab was an infusion-related reaction. One participant in each arm experienced an AE that led to treatment discontinuation.5

The results from the COMMODORE 1 study indicate that crovalimab maintained disease control in people switching from currently approved complement inhibitors.6 The data supports the consistent benefit–risk profile of crovalimab, as well as subcutaneous administration with the option to self-administer, as seen in the COMMODORE 2 study.

Roche also presented preliminary data from the COMMODORE Burden of Illness study. The data suggest that despite currently available C5 inhibitor treatments, people with PNH continue experiencing a diminished quality of life and considerable costs, and they may benefit from new treatment options.7

Global phase III data from the COMMODORE 1 and 2 studies in PNH will be submitted to regulatory authorities around the world. Positive data from a third phase III study evaluating crovalimab in PNH, the COMMODORE 3 study in China, were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on 10 December 2022. Data from the COMMODORE 3 study have been submitted via China’s Centre for Drug Evaluation Breakthrough Therapy Designation pathway. This submission has been accepted under Priority Review for approval consideration by China’s National Medical Products Administration.

About the COMMODORE 1 and 2 studies
The COMMODORE 2 study is a phase III, randomized, open-label study evaluating the efficacy and safety of crovalimab versus eculizumab in people with paroxysmal nocturnal hemoglobinuria (PNH) who have not been treated previously with C5 inhibitors. The 204 adults* enrolled in the study were randomized in a 2:1 ratio to be treated with either subcutaneous (SC) crovalimab every four weeks or intravenous (IV) eculizumab every two weeks. The six participants under 18 years old were included in a descriptive arm to be treated with SC crovalimab every four weeks.8

*Including two patients aged less than 18 years old enrolled before the revision of the protocol

The COMMODORE 1 study is a phase III, randomized, open-label study evaluating the safety of crovalimab in people with PNH switching from currently approved C5 inhibitors. The study included 89 people (18 years of age or older) currently treated with eculizumab, randomized in a 1:1 ratio to be treated with either SC crovalimab every four weeks or IV eculizumab every two weeks. In a non-randomized arm, the study also included pediatrics (<18 years of age) currently treated with eculizumab, people currently treated with ravulizumab, people currently treated with off-label doses of eculizumab (higher than the approved dose for PNH: more than 900mg per dose and/or more frequently than every two weeks), or people with known mutations in the C5 gene who do not respond to current therapies.9

About the COMMODORE Burden of Illness Study
The COMMODORE Burden of Illness (BOI) study will quantify the direct medical costs (e.g., treatment and hospitalization), direct nonmedical costs (e.g., travel), and indirect costs (e.g., impact on work productivity and family burden) associated with PNH for patients and care providers and determine the impact of PNH on health-related quality of life (HRQoL), in U.K., France, and Germany.10

About crovalimab
Crovalimab is an anti-C5 recycling antibody created with Chugai’s Recycling Antibody technology. Recycling antibodies are designed to achieve pH-dependent antigen binding so that a single antibody molecule can bind with the antigen multiple times, enabling a longer efficacy compared with a conventional antibody. Crovalimab is designed to target C5, a key component of the complement system, and is expected to control complement activity. It is also expected to reduce the treatment burden for patients and their caregivers through subcutaneous administration. Since crovalimab binds to complement C5 at a different site from existing antibody drugs, it can be an effective treatment option for patients with a specific C5 gene mutation (appears in approximately 3.2% of Japanese patients with PNH), which causes existing antibody drugs not to bind to C5.3,11
In addition to PNH, clinical trials are ongoing for atypical hemolytic uremic syndrome (aHUS). Overseas, Roche is conducting trials for sickle cell disease (SCD) and lupus nephritis.

About paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by intravascular hemolysis due to complement activation. It is caused by the clonal expansion of hematopoietic stem cells, driven by acquired mutations in the PIG-A gene.12 While symptoms may vary in each individual, there are typically two types. One is symptoms attributed to the characteristic hemolysis in PNH, such as hemoglobinuria and thrombosis. The other is hematopoietic failures similar to those associated with aplastic anemia. PNH may cause complications, including chronic kidney disease and pulmonary hypertension. In Japan, PNH is a rare disease that is listed as one of the designated intractable diseases (designated intractable disease 62). 959 individuals have been granted the medical care recipient certificate for PNH as of the end of 2021.

On June 12, 2023 Bluebird Bio presented its corporate presentation (Presentation, bluebird bio, JUN 12, 2023, View Source [SID1234632648]).

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On June 12, 2023 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders and viral diseases, reported an update on its ongoing clinical development programs evaluating Ampligen (rintatolimod), a dsRNA and highly selective TLR3 agonist immune-modulator with broad spectrum activity (Press release, AIM ImmunoTech, JUN 12, 2023, View Source [SID1234632642]).

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AIM Chief Executive Officer Thomas K. Equels commented, "We have made promising progress across multiple clinical fronts, and I am proud of the dedication of our team and their evident operational execution. Ampligen continues to demonstrate significant potential across multiple types of cancers, immune disorders and viral diseases. We are committed to advancing Ampligen’s development and are poised to achieve multiple key milestones in 2023."

Ampligen Phase 2 Study as a Therapy for Locally Advanced Pancreatic Cancer ("LAPC") (AMP-270)

The AMP-270 clinical trial is the Company’s randomized, open-label, controlled, parallel-arm study with the primary objective of comparing the efficacy of Ampligen versus a no treatment control group following FOLFIRINOX for subjects with locally advanced pancreatic adenocarcinoma. Secondary objectives include comparing safety and tolerability. AMP-270 is expected to enroll approximately 90 subjects in up to 30 centers across the United States and Europe.

The Company is recruiting patients for its AMP-270 Phase 2 study of Ampligen as a therapy for LAPC. The lead site at the University of Nebraska Medical Center is now open and actively working to enroll patients. The Gabrail Cancer & Research Center in Canton, Ohio is also recruiting patients.

Kelsey Klute, MD, Medical Director of the Pancreatic Diseases Specialty Clinic at Nebraska Medicine, commented, "We are pleased to join into what we believe is an important Phase 2 study that has the potential to address a much-needed treatment option for LAPC. Our team is actively working to enroll and treat patients on the study in a joint effort with all other clinical trial sites. We are encouraged by the potential of Ampligen and look forward to further exploring its potential in the treatment of LAPC."

AIM continues its efforts to open additional clinical sites at premier cancer centers across the United States and Europe. The Company remains optimistic for first patient enrollment in the second quarter of this year.

For more information about the AMP-270 please visit ClinicalTrials.gov and reference identifier NCT05494697.

Ampligen Phase 1 Study for the Treatment of Early-Stage Triple Negative Breast Cancer ("TNBC")

Ampligen is currently being evaluated in a Phase 1 study for TNBC by Roswell Park Comprehensive Cancer Center. The study is designed to evaluate the safety and tolerability of a combination of Ampligen and celecoxib with or without Intron A, when given along with chemotherapy. The primary endpoint was safety and tolerability. Secondary endpoints included pCR rate. Tumor and blood biomarkers were analyzed in exploratory studies. The goal of this approach is to increase survival. In November 2022, Roswell presented positive data at the SITC (Free SITC Whitepaper) 37th Annual Meeting demonstrating the chemokine-modulating regimen including Ampligen was well tolerated, with promising clinical activity of pathologic complete response (pCR) + microinvasive residual disease (ypTmic).

Roswell has now completed the study and is currently analyzing data. Based on current timelines, the Company anticipates Roswell will release – via publications – full study results before the end of the year.

For more information about the Phase 1 study of Ampligen for the treatment of TNBC, visit ClinicalTrials.gov and reference identified NCT04081389.

Ampligen Analysis Demonstrating Potential as a Maintenance Therapy After Systemic Chemotherapy in Patients with Metastatic and LAPC

A new analysis was recently presented in an abstract titled, "Immune Response in Stable Pancreatic Cancer after Rintatolimod Treatment," by Professor C.H.J. van Eijck, MD, PhD of Erasmus Medical Center at the 2023 Annual Pancreas Club Meeting held in Chicago, Illinois. Findings from the analysis demonstrated that treatment of patients with LAPC after FOLFIRINOX with Ampligen (rintatolimod) may induce markers of dendritic cells and T cells in a subgroup of patients. The absence of these markers may predict tumor progression after FOLFIRINOX, providing the future possibility of identifying pancreatic cancer patients who could potentially respond to Ampligen.

The results from the new analysis build on the previously reported peer-reviewed article "Rintatolimod (Ampligen) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program," published in March 2022 in the journal Cancers.

Ampligen as a Potential Therapy Against Ebola Virus Disease ("EVD")

The South African Patent and Trademark Office (CIPC) has granted patent No. 2022/01079, titled "Compositions and Methods Useful for Ebola Virus Infection." This pioneering patent recognizes the efficacy of AIM’s tdsRNA drug family, of which Ampligen is a member, as a potential solution to combat the devastating impact of Ebola outbreaks. Under the newly granted patent, a composition comprising tdsRNA may be used in a method that involves administering the composition to a subject to prevent, treat, inhibit, or attenuate an Ebola virus infection in that subject. Significantly, the composition may be used as a treatment for individuals already infected with the Ebola virus, or the composition may be used to prevent an Ebola infection.

About Ampligen

Ampligen is AIM’s dsRNA product candidate being developed for globally important cancers, viral diseases and disorders of the immune system. Ampligen has demonstrated in the clinic the potential for standalone efficacy in a number of solid tumors. Additionally, Ampligen has shown success in increasing survival rates and efficacy in the treatment of animal tumors when used in combination with checkpoint blockade therapies.

Ampligen is currently being evaluated as a combinational therapy for the treatment of a variety of solid tumor types in multiple clinical trials – both underway and planned – at major cancer research centers around the country. Ampligen is being used to treat pancreatic cancer patients in an Early Access Program approved by the Inspectorate of Healthcare in the Netherlands at Erasmus Medical Center. Additionally, Ampligen is also approved in Argentina for the treatment of severe chronic fatigue syndrome and is currently being evaluated in SARS-CoV-2/COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Post COVID Conditions.