FDA Grants Orphan Drug Designation to Bexmarilimab for Myelodysplastic Syndromes

The FDA has granted orphan drug designation to the investigational immunotherapy bexmarilimab as a potential therapeutic option for patients with myelodysplastic syndromes (MDS).1

Bexmarilimab is designed to bind to Clever-1, which is an immunosuppressive receptor found on macrophages that promotes tumor growth and metastases. Targeting Clever-1 could allow for the alteration of the tumor microenvironment by reprogramming macrophages to an immunostimulatory state.

The ongoing phase 1/2 BEXMAB trial (NCT05428969) is evaluating bexmarilimab in patients with MDS, chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML).

“Receiving FDA’s orphan drug designation for bexmarilimab for the treatment of MDS marks a significant milestone for Faron Pharmaceuticals as we continue to develop bexmarilimab for MDS and other cancers,” Petri Bono, MD, PhD, chief medical officer of Faron Pharmaceuticals, stated in a news release. “This FDA orphan drug designation, along with the previously granted FDA fast track designation, highlights our continued progress and reinforces our belief in the potential of bexmarilimab to address this significant unmet need for treatment of MDS. These designations allow us to receive important regulatory guidance for the development of bexmarilimab and potential additional market exclusivity upon approval.”

Data from BEXMAB presented at the 2024 ASH Annual Meeting showed that patients with MDS that was relapsed/refractory following treatment with a hypomethylating agent (HMA; n = 20) experienced an overall response rate (ORR) of 80% when treated with the combination of bexmarilimab and azacitidine.2 Additionally, this patient population achieved a median overall survival of 13.4 months.

The multicenter, open-label BEXMAB trial is enrolling patients at least 18 years of age with morphologically confirmed, intermediate-, high-, and very high–risk MDS per revised International Prognostic Scoring System criteria or morphologically confirmed CMML-2 with an indication for azacitidine.3 Patients with CMML or MDS need to have lack of response to an HMA-containing regimen. The study is also including patients with morphologically confirmed relapsed/refractory AML following at least 1 line of prior therapy who are indicated for azacitidine; or patients with morphologically confirmed AML who are unfit for induction therapy and are indicated for azacitidine plus venetoclax (Venclexta). Adequate renal and liver function are required for all patients.

Key exclusion criteria consist of acute promyelocytic leukemia or myeloproliferative CMML; an ECOG performance status of 3 or higher; receipt of allogeneic stem cell transplant within 6 months of enrollment; active autoimmune disorder; and receipt of any immunotherapy or investigational therapy within 28 days of first study treatment.

In phase 1, bexmarilimab was evaluated at 4 different dose levels in combination with standard-of-care azacitidine; bexmarilimab was given once per week, then once every 2 weeks during 28-day cycles. However, patients with newly diagnosed AML who were unfit for induction therapy received bexmarilimab at 1 of 4 dose levels plus azacitidine and venetoclax.

In phase 2, patients are receiving bexmarilimab at a dose determined in phase 1 in combination with venetoclax and/or azacitidine.

The study’s primary end points include dose-limiting toxicities; safety; complete response (CR) rate for patients with MDS or CMML-2; ORR for patients with MDS or CMML who progressed on a prior HMA; CR with incomplete blood count recovery rate in patients with relapsed/refractory AML; and minimal residual disease status for those with newly diagnosed AML.

Topline data for patients with newly diagnosed MDS or relapsed/refractory MDS following progression on an HMA are expected to be reported in April 2025.1

References

1. Inside information: FDA grants orphan drug designation for bexmarilimab in MDS. News release. Faron Pharmaceuticals. March 3, 2025. Accessed March 4, 2025. https://faron.com/releases-and-publications/inside-information-fda-grants-orphan-drug-designation-for-bexmarilimab-in-mds/
2. Positive phase 2 interim results from BEXMAB trial. News release. Faron Pharmaceuticals. November 27, 2024. Accessed March 4, 2025. https://faron.com/releases-and-publications/positive-phase-2-interim-results-from-bexmab-trial/
3. 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 March 4, 2025. https://clinicaltrials.gov/study/NCT05428969