SLS009 Earns EMA Orphan Drug Designation for AML

Angelos Stergiou, MD, ScD hc

Following a positive opinion issued by the European Medicines Agency (EMA), the European Commission has granted orphan drug designation to the novel and highly selective CDK9 inhibitor SLS009 as a potential treatment option for patients with acute myeloid leukemia (AML).¹

“We are thrilled to receive orphan drug designation from the EMA for the treatment of AML. This designation along with the recently announced strong preliminary phase 2 data and previous FDA orphan drug designation reinforces our continued progress and commitment to developing SLS009 as a potential treatment for AML,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS, stated in a news release. “We look forward to working closely with the EMA and the FDA to advance SLS009 clinical development and ultimately deliver it to the patients who need it most. To that end, we remain on track to share further data around SLS009 in the third quarter of this year.”

The phase 2a portion of a phase 1/2 trial (NCT04588922) is evaluating SLS009 in combination with venetoclax (Venclexta) and azacitidine (Vidaza) for the treatment of patients with relapsed/refractory AML. The study completed enrollment in the phase 2a portion in June 2024.²

Initial data from the study showed that all evaluable patients treated across all dose levels of SLS009 (n = 27) experienced an overall response rate (ORR) of 29.6%; in patients treated with SLS009 at 30 mg twice per week, the highest ORR observed was 50%.

Patients treated with 60 mg of SLS009 once per week achieved a median overall survival (OS) of 5.4 months, besting the expected median OS of 2.5 months for patients who are relapsed/refractory to venetoclax in combination with hypomethylating agents.

In patients treated with SLS009 at 60 mg once per week (n = 9), the ORR was 33%, and the median OS was not reached (NR). For those treated with 30 mg of SLS009 twice per week (n = 8), the ORR was 50%, and the median OS was NR.

Notably, of the 8 patients who experienced a response at any dose level, 6 harbored myelodysplasia-related somatic mutations, including 5 patients with ASXL1 mutations. Among patients harboring ASXL1 mutations who were treated at 30 mg twice per week, the ORR was 100%.

The open-label, single-arm, multicenter trial is enrolling patients at least 18 years of age, as well as pediatric patients between 12 and 18 years of age with a body mass of at least 40 kg. In group 3, patients are required to have AML that is relapsed/refractory to venetoclax-containing regimens. Cohort 4 of group 3 includes patients with AML harboring ASXL1 mutations whose disease is relapsed/refractory to venetoclax-containing regimens, and cohort 5 features patients with myelodysplasia-related somatic mutations other than ASXL1 who are relapsed/refractory to venetoclax-containing regimens.³

Key exclusion criteria include bulky disease of at least 10 cm that requires cytoreductive therapy; symptomatic central nervous system (CNS) metastases or primary CNS lymphoma, leptomeningeal disease, or spinal cord compression; severe cardiovascular disease within 6 months of enrollment; and concomitant exposure to strong CYP3A4 inhibitors and strong inducers within 7 days prior to the first study dose.

Within group 3, patients in cohort 1 are receiving SLS009 at 45 mg once per week in combination with venetoclax and azacitidine. Those in cohort 2 of group 3 are being administered 60 mg of SLS009 once per week plus venetoclax and azacitidine. In cohorts 3, 4, and 5, SLS009 is being given at 30 mg twice per week plus venetoclax and azacitidine.

The primary end points of the study are the incidence of dose-limiting toxicities (DLTs) and all adverse effects (AEs). Secondary end points include pharmacokinetics, ORR, duration of response, progression-free survival, and OS.

Regarding safety, data from phase 2a showed that SLS009 was generally well tolerated, and no new safety signals were reported across all dose levels. No DLTs or high-grade, treatment-related, nonhematologic AEs were reported. Hematologic AEs were consistent with those observed with venetoclax-containing regimens.

References

1. SELLAS receives European Medicines Agency orphan drug designation for SLS009 for the treatment of acute myeloid leukemia. News release. SELLAS. July 8, 2024. Accessed July 11, 2024. https://ir.sellaslifesciences.com/news/News-Details/2024/SELLAS-Receives-European-Medicines-Agency-Orphan-Drug-Designation-for-SLS009-for-the-Treatment-of-Acute-Myeloid-Leukemia/default.aspx
2. SELLAS announces completion of enrollment and initial positive data in phase 2a trial of SLS009 in r/r AML. News release. SELLAS. June 10, 2024. Accessed July 11, 2024. https://ir.sellaslifesciences.com/news/News-Details/2024/SELLAS-Announces-Completion-of-Enrollment-and-Initial-Positive-Data-in-Phase-2a-Trial-of-SLS009-in-rr-AML/default.aspx
3. A study of GFH009 in patients with hematologic malignancies. ClinicalTrials.gov. Updated June 14, 2024. Accessed July 11, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04588922