Keros Therapeutics Presents Clinical Data from its Elritercept Program at the 66th American Society of Hematology Annual Meeting and Exposition
Keros Therapeutics (KROS) presented data from two ongoing Phase 2 clinical trials of elritercept at the 66th ASH Annual Meeting. The first trial in lower-risk myelodysplastic syndromes (MDS) showed that 55.2% of patients achieved overall erythroid response, with a median transfusion independence duration of 134.1 weeks. Of high transfusion burden patients, 31.4% achieved transfusion independence for at least eight weeks.
The second trial in myelofibrosis (MF) demonstrated that 82.8% of non-transfusion dependent patients showed increased hemoglobin levels, while 63.4% of transfusion-dependent patients showed reduced transfusion burden. Additionally, 40% of patients showed reduced spleen volume, and 66.7% experienced reduced disease symptoms at week 24.
Elritercept was generally well-tolerated in both trials, with most adverse events being mild to moderate.
Keros Therapeutics (KROS) ha presentato i dati di due studi clinici di fase 2 in corso su elritercept durante il 66° Congresso Annuale dell'ASH. Il primo studio sui sindromi mielodisplastiche (MDS) a basso rischio ha mostrato che il 55,2% dei pazienti ha raggiunto una risposta eritroide complessiva, con una durata mediana di indipendenza dalle trasfusioni di 134,1 settimane. Tra i pazienti con elevato fabbisogno trasfusionale, il 31,4% ha ottenuto indipendenza dalle trasfusioni per almeno otto settimane.
Il secondo studio sulla mielofibrosi (MF) ha dimostrato che l'82,8% dei pazienti non dipendenti da trasfusioni ha mostrato un aumento dei livelli di emoglobina, mentre il 63,4% dei pazienti dipendenti da trasfusioni ha mostrato una riduzione del fabbisogno trasfusionale. Inoltre, il 40% dei pazienti ha mostrato una riduzione del volume della milza e il 66,7% ha sperimentato una diminuzione dei sintomi della malattia alla settimana 24.
Elritercept è stato generalmente ben tollerato in entrambi gli studi, con la maggior parte degli eventi avversi classificati come lievi o moderati.
Keros Therapeutics (KROS) presentó datos de dos ensayos clínicos de fase 2 en curso sobre elritercept en la 66ª Reunión Anual de la ASH. El primer ensayo en síndromes mielodisplásicos (MDS) de bajo riesgo mostró que el 55,2% de los pacientes logró una respuesta eritroide general, con una duración mediana de independencia de transfusiones de 134,1 semanas. De los pacientes con alta carga transfusional, el 31,4% logró independencia de transfusiones durante al menos ocho semanas.
El segundo ensayo en mielofibrosis (MF) demostró que el 82,8% de los pacientes no dependientes de transfusiones mostraron niveles de hemoglobina aumentados, mientras que el 63,4% de los pacientes dependientes de transfusiones mostraron una reducción en la carga transfusional. Además, el 40% de los pacientes mostró una reducción en el volumen del bazo y el 66,7% experimentó una disminución de los síntomas de la enfermedad a la semana 24.
Elritercept fue generalmente bien tolerado en ambos ensayos, con la mayoría de los eventos adversos siendo leves a moderados.
Keros Therapeutics (KROS)는 66회 ASH 연례 회의에서 elritercept에 대한 진행중인 2상 임상 시험 두 가지의 데이터를 발표했습니다. 저위험 골수형성이상증후군(MDS)에 대한 첫 번째 시험에서 55.2%의 환자가 전체적으로 적혈구 반응을 나타냈고, 효부의 독립 지속 기간은 134.1주였습니다. 고전혈 수요 환자 중 31.4%가 적어도 8주 동안 수혈 독립성을 달성했습니다.
두 번째 시험인 골수섬유증(MF)에서는 수혈에 의존하지 않는 환자의 82.8%가 헤모글로빈 수치가 상승한 반면, 수혈에 의존하는 환자의 63.4%가 수혈 부담 감소를 나타냈습니다. 또한 40%의 환자가 비장 크기 감소를 나타냈고, 24주차에 66.7%가 질병 증상 완화를 경험했습니다.
Elritercept는 두 차례 임상 시험에서 일반적으로 잘 견뎌졌으며, 대부분의 부작용은 경증에서 중증으로 분류되었습니다.
Keros Therapeutics (KROS) a présenté des données de deux essais cliniques de phase 2 en cours sur elritercept lors de la 66e Réunion Annuelle de l'ASH. Le premier essai sur les syndromes myélodysplasiques (MDS) à faible risque a montré que 55,2 % des patients ont atteint une réponse érythroïde globale, avec une durée médiane d'indépendance transfusionnelle de 134,1 semaines. Parmi les patients avec une forte charge transfusionnelle, 31,4 % ont atteint une indépendance transfusionnelle pendant au moins huit semaines.
Le deuxième essai sur la myélofibrose (MF) a démontré que 82,8 % des patients non dépendants des transfusions ont montré des niveaux d'hémoglobine augmentés, tandis que 63,4 % des patients dépendants des transfusions ont connu une réduction de leur charge transfusionnelle. De plus, 40 % des patients ont montré une réduction du volume de la rate et 66,7 % ont ressenti une diminution des symptômes de la maladie à la semaine 24.
Elritercept a été généralement bien toléré dans les deux essais, la plupart des événements indésirables étant légers à modérés.
Keros Therapeutics (KROS) präsentierte Daten aus zwei laufenden Phase-2-Studien zu Elritercept auf dem 66. ASH-Jahrestreffen. Die erste Studie über niedrigrisikobehaftete myelodysplastische Syndrome (MDS) zeigte, dass 55,2% der Patienten eine allgemeine erythroide Antwort erreichten, wobei die mediane Dauer der Transfusionsunabhängigkeit bei 134,1 Wochen lag. Von den Patienten mit hoher Transfusionslast erreichten 31,4% eine Transfusionsunabhängigkeit von mindestens acht Wochen.
Die zweite Studie zur Myelofibrose (MF) zeigte, dass 82,8% der nicht transfusionsabhängigen Patienten erhöhte Hämoglobinwerte aufwiesen, während 63,4% der transfusionsabhängigen Patienten eine reduzierte Transfusionslast zeigten. Darüber hinaus zeigten 40% der Patienten eine Verringerung des Milzvolumens, und 66,7% berichteten nach 24 Wochen von einer Abnahme der Krankheitssymptome.
Elritercept wurde in beiden Studien allgemein gut vertragen, wobei die meisten unerwünschten Ereignisse mild bis moderat waren.
- 55.2% of MDS patients achieved overall erythroid response
- Median transfusion independence duration of 134.1 weeks in MDS trial
- 82.8% of non-transfusion dependent MF patients showed increased hemoglobin levels
- 63.4% of transfusion-dependent MF patients showed reduced transfusion burden
- 40% of MF patients demonstrated reduced spleen volume
- 66.7% of MF patients showed reduced disease symptoms
- Four fatal treatment-emergent adverse events in MDS trial (deemed unrelated)
- Six fatal treatment-emergent adverse events in MF trial (deemed unrelated)
- 12 patients experienced Grade 3 or higher treatment-related thrombocytopenia in MF trial
Insights
The clinical data for elritercept in MDS and MF patients demonstrates significant therapeutic potential. The 55.2% overall erythroid response rate and median transfusion independence duration of 134.1 weeks in MDS patients are particularly impressive, especially considering the difficult-to-treat population with high transfusion burden. The durability of responses is noteworthy, with 92.3% of ongoing TI responses lasting over 52 weeks.
The drug's efficacy in non-transfused patients is remarkable, with 93.3% achieving hemoglobin increases >1.0 g/dL. The safety profile appears manageable, with most adverse events being mild to moderate. The multi-lineage benefits observed across platelets and neutrophils, coupled with improvements in quality of life measures, suggest a comprehensive treatment effect.
This data release significantly strengthens Keros's market position in the hematology space. The robust efficacy data supports the upcoming Phase 3 RENEW trial, potentially accelerating the path to commercialization. The dual potential in both MDS and MF markets expands the commercial opportunity substantially.
The durability of response is particularly important from a commercial perspective, as it suggests potential for sustained revenue streams once approved. The quality of life improvements and manageable safety profile could support favorable pricing and reimbursement decisions. With a market cap of
- Elritercept demonstrated a durable transfusion independence in lower-risk myelodysplastic syndromes, including in patients with high transfusion burden, with a median duration of response of 134.1 weeks
- Durable clinical responses were associated with improvements in patient-reported measures of fatigue in MDS patients early, and with continued improvement over time
- Data from ongoing Phase 2 clinical trial in myelofibrosis continue to demonstrate that elritercept can potentially ameliorate ineffective hematopoiesis and address cytopenias, and also provide broader clinical benefit, as supported by observed reductions in spleen volume and improved total symptom scores
LEXINGTON, Mass., Dec. 09, 2024 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. (“Keros” or the “Company”) (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta (“TGF-ß”) family of proteins, today announced that it presented additional data from its two ongoing Phase 2 clinical trials of elritercept (KER-050), one in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (“MDS”) and one in patients with myelofibrosis (“MF”), at the 66th American Society of Hematology Annual Meeting and Exposition (“ASH”), held in person in San Diego, California and virtually from December 7-10, 2024.
“The data we presented at ASH supports the differentiated profile of elritercept in both MDS and MF,” said Jasbir S. Seehra, Ph.D., Chair and Chief Executive Officer. “We look forward to commencing enrollment of our Phase 3 RENEW clinical trial evaluating elritercept in adult patients with transfusion-dependent anemia with very low-, low-, or intermediate-risk MDS soon, so that we can take the next step towards bringing this potential treatment option to patients.”
Clinical Presentations
- Improvements in Hematological Parameters and Quality of Life (“QoL”) with Elritercept: Results from an Ongoing Phase 2 Trial in Participants with Lower-Risk MDS
This ongoing, open-label, two-part, Phase 2 clinical trial is evaluating elritercept in patients with very low-, low-, or intermediate-risk MDS. As of August 30, 2024 (the “data cut-off date”), 95 patients had received at least one dose of elritercept at the recommended Part 2 dose (“RP2D”) (collectively, the “safety population”). Of these patients in the safety population, 87 had completed at least 24 weeks of treatment or discontinued as of the data cut-off date (collectively, the modified intent-to-treat 24-week population, or the “mITT24 patients”). Data for hematological response and markers of hematopoiesis were presented from exploratory analyses of these mITT24 patients. All data presented from this trial is as of the data cut-off date.
Of the 95 patients in the safety population,
Elritercept was generally well-tolerated in the safety population. There were four cases of fatal treatment-emergent adverse events (“TEAEs”) in the trial that were all deemed unrelated to treatment. The most commonly reported TEAEs (in ≥
Additional data from the mITT24 patients include:
39.1% (n=27/69) of the TI-evaluable patients achieved TI for at least eight weeks over the first 24 weeks of treatment.- Of the patients with HTB,
31.4% (n=16/51) achieved TI for at least eight weeks during the first 24 weeks of treatment. Eight of those 16 patients (50.0% ) achieved TI for at least 24 weeks over the first 48 weeks of treatment. - Of the TI-evaluable patients with baseline erythropoietin level less than 500 U/L,
47.3% (n=26/55) achieved TI for at least eight weeks over the first 24 weeks of treatment. Of the TI-evaluable patients with baseline erythropoietin level less than 500 U/L and HTB,38.5% (n=15/39) achieved TI for at least eight weeks over the first 24 weeks of treatment.
The FACIT-Fatigue scale, a measure of self-reported fatigue and its impact upon daily activities and function, was utilized to assess health-related quality of life, including in a subgroup of patients (n=17) achieving TI for at least 24 weeks over the first 48 weeks of treatment. Patients in this subgroup showed clinically meaningful improvements in QoL, and meaningful improvements in FACIT-Fatigue were observed early and generally continued to improve over time in patients with more durable TI responses.
The majority of patients enrolled in this ongoing trial had HTB and/or multi-lineage dysplasia, indicating a difficult-to-treat trial population. Durable TI responses continued to be observed in a broad range of patients with lower-risk MDS, including in those with HTB, which support the potential for elritercept to ameliorate ineffective hematopoiesis across multiple lineages in patients with MDS. These Phase 2 data further support the rationale for the planned Phase 3 RENEW registrational trial of elritercept in transfusion-dependent patients with very low-, low-, and intermediate risk MDS.
- Hematologic Improvement and Fatigue Reduction with Elritercept in Participants with Lower-Risk MDS with Non-Transfusion Dependent Anemia: New Analyses from an Ongoing Phase 2 Trial
In a subgroup analysis of patients that were non-transfused (“NT”) at baseline, treatment with elritercept showed:
- Robust hematological responses observed with
93.3% (n=14/15) of NT patients having an increase greater than 1.0 g/dL and86.7% (n=13/15) having an HI-E response. - Durable HI-E responses observed with elritercept treatment with
100% (n=13/13) achieving a continuous response duration of greater than 24 weeks and76.9% (n=10/13) achieving a cumulative response duration greater than 52 weeks. - Sustained and durable increases in hemoglobin and soluble transferrin receptor, a marker of erythropoietic activity, were observed in NT participants.
- Overall improvement in mean platelet and neutrophil counts along with decreases in mean ferritin and hepcidin were observed after only one dose and were generally maintained through 48 weeks, demonstrating that elritercept has the potential to address ineffective hematopoiesis across multiple lineages and improve iron utilization and reduce inflammation.
- NT patients achieved meaningful improvements in FACIT-Fatigue scores, with improvements seen early, generally within the first two treatment cycles.
- Hematological Improvement and Other Clinical Benefits of Elrtiercept as Monotherapy and in Combination with Ruxolitinib in Participants with Myelofibrosis from the Ongoing Phase 2 RESTORE Trial
This ongoing, open-label, two-part Phase 2 clinical trial is evaluating elritercept administered with or without ruxolitinib in patients with MF who have anemia and were either currently on, failed, or ineligible for ruxolitinib at baseline. Safety data are presented for all patients that received at least one dose of elritercept (n=73) as of the August 30, 2024 data cutoff date. Evaluations of markers of hematopoiesis and anemia over 12 weeks, along with measurements of spleen volume and symptom scores (by the MF-symptom assessment form-Total Symptom Score, or “MF-SAF-TSS”) over 24 weeks, were presented for dose levels 1 through 4 in Part 1 and the RP2D, ranging from 0.75 mg/kg to 5.0 mg/kg (collectively, the “efficacy evaluable patients”). Enrollment of Part 1 of the trial, the dose escalation portion, is complete. Part 2, the dose expansion portion, is open and enrolling with an RP2D of 3.75 mg/kg with the option to up-titrate to 5.0 mg/kg. All data presented from this trial is as of the data cutoff date.
Elritercept was generally well-tolerated by the safety population. There were six cases of fatal TEAEs in the trial that were each deemed unrelated to treatment. The most commonly reported TEAEs (in ≥
Additional data from the efficacy evaluable patients include:
- Increases in hemoglobin were observed in
82.8% (n=24/29) of evaluable non-transfusion dependent patients in both arms over a 12-week period within the first 24 weeks, suggesting that elritercept has the potential to address anemia due to MF and ruxolitinib-associated anemia. 63.4% (n=26/41) of patients that received at least three RBC units per 12 weeks at baseline in both arms and all dose levels tested showed reductions in transfusion burden over 12 weeks within the first 24 weeks.24.4% (n=10/41) of the patients who showed reductions in transfusion burdens achieved TI.- Additionally, within the subgroup of these patients in the combination arm who received a starting dose of 3.0 mg/kg of elritercept or higher,
62.5% (n=10/16) had reductions of50% or greater, and37.5% (n=6/16) achieved TI.
- Additionally, within the subgroup of these patients in the combination arm who received a starting dose of 3.0 mg/kg of elritercept or higher,
- At week 24, reduction in spleen volume was observed in
40% (n=8/20) of patients with baseline spleen size ≥ 450 cm3 and a week 24 spleen assessment, including three patients who had reductions of35% or greater. Reductions in spleen volume in the combination arm generally occurred without an increase in ruxolitinib dose.- For evaluable patients in the combination arm with a starting dose of 3.0 mg/kg of elritercept or higher,
88% (n=7/8) had some reduction in spleen size at week 24
- For evaluable patients in the combination arm with a starting dose of 3.0 mg/kg of elritercept or higher,
- At week 24, reduction in disease symptoms was observed in
66.7% (n=18/27) of patients with at least two symptoms with an average score ≥ 3 or an average total score of ≥ 10 on the MF-SAF-TSS questionnaire at baseline and a week 24 MF-SAF-TSS assessment. Five patients had reductions of at least50% , including three in the monotherapy arm and two in the combination arm.
The data support the potential of elritercept to ameliorate ineffective hematopoiesis and address cytopenias due to MF and associated with ruxolitinib, and provide broader clinical benefit in patients, as supported by the observed reduction in spleen volume and improvement in total symptom scores.
About the Ongoing Phase 2 Clinical Trial of Elritercept in Patients with MDS (NCT04419649)
Keros is conducting an open label, two-part, multiple ascending dose Phase 2 clinical trial to evaluate elritercept in patients with very low-, low-, or intermediate-risk MDS who either have or have not previously received treatment with an erythroid stimulating agent.
The primary objective of this trial is to assess the safety and tolerability of elritercept in patients with MDS that are RS positive or non-RS. The primary objective of Part 2 of this trial is confirmation of the safety and tolerability of the RP2D (3.75 mg/kg and 5.0 mg/kg). The secondary objectives of this trial are to evaluate the pharmacokinetics, pharmacodynamics and efficacy of elritercept.
About the Ongoing Phase 2 Clinical Trial of Elritercept in Patients with MF-Associated Cytopenias (RESTORE trial; NCT05037760)
Keros is conducting an open label, two-part, multiple ascending dose Phase 2 clinical trial to evaluate elritercept as a monotherapy and in combination with ruxolitinib in patients with MF-associated cytopenias.
The primary objective of this trial is to assess the safety and tolerability of elritercept in patients with MF-associated cytopenias. The primary objective of Part 2 of this trial is confirmation of the safety and tolerability of the RP2D (3.75 mg/kg and 5.0 mg/kg). The secondary objectives of this trial are to evaluate the pharmacokinetics, pharmacodynamics and efficacy of elritercept administered with or without ruxolitinib.
About Elritercept
Elritercept is an engineered ligand trap comprised of a modified ligand-binding domain of the TGF-ß receptor known as activin receptor type IIA that is fused to the portion of the human antibody known as the Fc domain. Elritercept is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with MF.
About Keros Therapeutics, Inc.
Keros is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the TGF-ß family of proteins. We are a leader in understanding the role of the TGF-ß family of proteins, which are master regulators of the growth, repair and maintenance of a number of tissues, including blood, bone, skeletal muscle, adipose and heart tissue. By leveraging this understanding, we have discovered and are developing protein therapeutics that have the potential to provide meaningful and potentially disease-modifying benefit to patients. Elritercept is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with MF. Cibotercept (KER-012) is being developed for the treatment of pulmonary arterial hypertension and for the treatment of cardiovascular disorders. KER-065 is being developed for the treatment of obesity and for the treatment of neuromuscular diseases.
Cautionary Note Regarding Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as “expect,” “enable,” “forward,” “potential” and “will” or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: Keros’ expectations regarding the design, objectives, timing, results and outcomes of its clinical trials for elritercept, including the Phase 2 RESTORE trial and the Phase 3 RENEW trial; the differentiated profile of elritercept in both MDS and MF; the potential of elritercept to ameliorate ineffective hematopoiesis across multiple lineages in patients with MDS, improve iron utilization, reduce inflammation and improve quality of life in patients with lower-risk MDS; and the potential of elritercept to address anemia due to MF- and ruxolitinib-associated anemia, and to provide broader clinical benefit to patients with MF. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Keros’ limited operating history and historical losses; Keros’ ability to raise additional funding to complete the development and any commercialization of its product candidates; Keros’ dependence on the success of its product candidates, cibotercept, elritercept and KER-065; that Keros may be delayed in initiating, enrolling or completing any clinical trials; the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials; competition from third parties that are developing products for similar uses; Keros’ ability to obtain, maintain and protect its intellectual property; and Keros’ dependence on third parties in connection with manufacturing, clinical trials and preclinical studies.
These and other risks are described more fully in Keros’ filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q, filed with the SEC on November 6, 2024, and its other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Keros undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Investor Contact:
Justin Frantz
jfrantz@kerostx.com
617-221-6042
FAQ
What were the main results of Keros Therapeutics' (KROS) elritercept Phase 2 trial in MDS?
How effective was elritercept (KROS) in the Phase 2 myelofibrosis trial?
What were the safety results for elritercept (KROS) in the Phase 2 trials?
