The European Medicines Agency (EMA) Committee for Orphan Medicinal Products has granted orphan drug designation to AB8939 for the treatment of acute myeloid leukemia (AML), AB Science announced on April 23, 2025. This designation follows a similar status previously awarded by the US Food and Drug Administration (FDA).
The EMA designation represents a significant milestone for AB8939, as it acknowledges the drug's potential to offer substantial benefits to AML patients beyond existing treatment options. Unlike the FDA's orphan designation process, the EMA's criteria are particularly stringent, requiring evidence that the candidate provides clinically relevant advantages or makes major contributions to patient care compared to authorized treatments.
Promising Preclinical Evidence
AB Science presented compelling preclinical data demonstrating AB8939's effectiveness against resistant AML cells. In laboratory studies, 45% of vincristine-resistant cells and 66% of cytarabine-resistant cells responded to AB8939 treatment, including those with complex genetic mutations such as MECOM and TP53, which typically indicate poor prognosis.
In xenograft mouse models derived from refractory AML patients, AB8939 demonstrated tumor reduction and prolonged survival, even in cases resistant to cytarabine. The drug also showed additive effects when combined with standard treatments including cytarabine, azacitidine (Vidaza®), and venetoclax (Venclexta®).
Professor Olivier Hermine, President of AB Science's Scientific Committee and Head of the Hematology Department at Necker Hospital, emphasized the significance of these findings: "This designation testifies to the potential of AB8939 for the treatment of AML. Indeed, AB8939 has shown activity as a monotherapy on Ara-C-resistant patient lines, including in unfavorable genetic situations that have resisted all treatments administered to date, as well as a synergistic effect with the reference treatments."
Unique Mechanism of Action
AB8939 represents a novel approach to AML treatment through its dual mechanism of action. The synthetic molecule targets cancer cells by destabilizing microtubules essential for cell division while simultaneously inhibiting enzymes (ALDH1A1 and ALDH2) critical for cancer stem cell maintenance and survival.
Notably, unlike venetoclax, AB8939 does not appear to cause blood toxicity (hematotoxicity), a significant advantage for AML patients who often struggle with treatment-related cytopenias. The drug's synergistic action with existing therapies further enhances its potential clinical utility.
Clinical Development Status
AB Science has already initiated clinical evaluation of AB8939, with preliminary efficacy and safety data from the phase 1 trial as a monotherapy. The study has explored both 3-day treatment cycles (stage 1) and 14-day treatment cycles (stage 2).
The ongoing clinical program will now advance to evaluate AB8939 in combination with reference treatments in refractory patients, potentially addressing a significant unmet need in AML management.
Benefits of Orphan Drug Designation
The European orphan drug designation provides AB Science with several advantages, including scientific advice at reduced fees, direct access to centralized marketing authorization procedures, and eligibility for financial incentives to support research and development.
If AB8939 maintains its orphan designation through marketing authorization, it would receive 10 years of market exclusivity in the European Union. This protection represents a significant commercial advantage for AB Science, a Paris-based pharmaceutical company specializing in protein kinase inhibitors.
AML Treatment Landscape
Acute myeloid leukemia remains a challenging hematologic malignancy with limited treatment options, particularly for patients with refractory disease or unfavorable genetic profiles. Standard treatments like cytarabine, azacitidine, and venetoclax have improved outcomes for some patients, but resistance remains a significant obstacle.
The development of AB8939 addresses this critical gap in the treatment landscape, potentially offering new hope for patients with limited therapeutic options. The drug's activity against resistant cells and favorable toxicity profile could position it as an important addition to the AML treatment armamentarium.
As AB8939 progresses through clinical development, the medical community will be watching closely to see if its promising preclinical profile translates into meaningful clinical benefits for patients with this aggressive form of leukemia.
