Bexmarilimab Plus Azacitidine Meets ORR End Point in R/R Higher-Risk MDS

Bexmarilimab Plus Azacitidine in R/R

Higher-Risk MDS | Image credit:

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Treatment with bexmarilimab (FP-1305) plus standard-of-care (SOC) azacitidine elicited overall responses in patients with relapsed/refractory higher-risk myelodysplastic syndrome (MDS), meeting the primary end point of the phase 2 BEXMAB trial (NCT05428969).1 Additionally, patients with treatment-naive higher-risk MDS treated on the study also experienced a high level of response.

Topline findings from the phase 2 analysis demonstrated that patients with relapsed/refractory disease achieved an overall response rate (ORR) of 63%, and the median overall survival (OS) was consistent with previously reported data from this population. Additionally, patients with treatment-naive higher-risk MDS given bexmarilimab plus azacitidine experienced an ORR of 76%.

At the time of this analysis, a considerable number of patients remained early on treatment, which could lead to deepened responses over time. The combination regimen remained well tolerated and has not led to any dose-limiting toxicities (DLTs).

Faron Pharmaceuticals, the drug’s developer, has submitted the full dataset for presentation at the 2025 ASCO Annual Meeting.

“This is one of the strongest datasets ever seen in an all-comer population of treatment-resistant high-risk MDS,” Juho Jalkanen, MD, PhD, chief executive officer of Faron Pharmaceuticals, stated in a news release. “There is a significant unmet need in the treatment of high-risk MDS, as drug development in high-risk MDS and macrophage re-programming has proven to be extremely challenging, with a lot of previous failures. What really makes bexmarilimab stand out in this field is its good safety profile combined with very high efficacy, especially in last-line high-risk MDS. This [reinforces our] conviction that bexmarilimab is the long-awaited drug to overcome treatment resistance [in this disease setting].”

Data from BEXMAB were previously presented at the 2024 ASH Annual Meeting, and they demonstrated an ORR of 80% with the combination among patients with MDS who were relapsed/refractory following treatment with a hypomethylating agent (HMA; n = 20).2 The majority of responses were deep and durable, with 70% of responders achieving a complete response (CR), marrow CR, or partial response. The estimated median OS for this patient population was 13.4 months.

In March 2025, the FDA granted orphan drug designation to bexmarilimab as a potential therapeutic option for patients with MDS.3The agent also received FDA orphan drug designation for acute myeloid leukemia (AML) in August 2023.4

BEXMAB Trial Overview

BEXMAB is an ongoing, multicenter, open-label trial evaluating the macrophage-targeting agent bexmarilimab in combination with SOC azacitidine or venetoclax (Venclexta) in patients with advanced myeloid malignancies, including MDS, chronic myelomonocytic leukemia (CMML), and AML.5

The study is enrolling patients at least 18 years of age with morphologically confirmed intermediate-, high-, or very high–risk MDS per revised International Prognostic Scoring System criteria; or with CMML-2 requiring azacitidine. Notably, those with MDS or CMML must have progressed on a prior HMA regimen. Patients with relapsed/refractory AML following 1 or more prior lines of therapy and those with newly diagnosed AML who are unfit for induction and are indicated for azacitidine plus venetoclax are also eligible. Adequate renal and hepatic function is required.

In the phase 1 portion of the study, bexmarilimab was administered at 4 dose levels in combination with azacitidine, initially with weekly dosing, followed by biweekly administration for each 28-day cycle. For patients with newly diagnosed AML who were unfit for induction therapy, bexmarilimab at 1 of the 4 dose levels was combined with azacitidine and venetoclax.

The phase 2 dose-expansion portion of the study is evaluating bexmarilimab at the recommended phase 2 dose alongside venetoclax and/or azacitidine for each of the indications selected to move forward.

The study’s primary end points include the incidence of DLTs, overall safety, CR rate in MDS and CMML-2, ORR in MDS or CMML with progression on an HMA, CR with incomplete hematologic recovery in relapsed/refractory AML, and minimal residual disease status in newly diagnosed AML.

References

1. Inside information: Faron Announces positive phase II results in higher-risk myelodysplastic syndrome. News release. Faron Pharmaceuticals. April 15, 2025. Accessed April 15, 2025. https://faron.com/releases-and-publications/inside-information-faron-announces-positive-phase-ii-results-in-higher-risk-myelodysplastic-syndrome/
2. Faron presents full analysis of positive phase 2 interim data from BEXMAB trial at the 66th American Society of Hematology (ASH) Annual Meeting. News Release. December 10, 2024. Accessed April 15, 2025. https://faron.com/releases-and-publications/faron-presents-bexmab-data-at-ash-annual-meeting/
3. Inside information: FDA grants orphan drug designation for bexmarilimab in MDS. News release. Faron Pharmaceuticals. March 3, 2025. Accessed April 15, 2025. https://faron.com/releases-and-publications/inside-information-fda-grants-orphan-drug-designation-for-bexmarilimab-in-mds/
4. Faron receives FDA orphan drug designation for bexmarilimab in acute myeloid leukemia. News release. Faron Pharmaceuticals. August 29, 2023. Accessed April 15, 2025. https://otp.tools.investis.com/clients/uk/faron2/rns/regulatory-story.aspx?cid=2223&newsid=1711777
5. A study to assess safety, tolerability and preliminary efficacy of bexmarilimab in combination with standard of care in patients with hematological malignancies (BEXMAB). ClinicalTrials.gov. Updated January 16, 2025. Accessed April 15, 2025. https://clinicaltrials.gov/study/NCT05428969