FDA Grants Rare Pediatric Disease Designation to SLS009 in Pediatric AML

• The FDA has granted SLS009 (formerly GFH009) a rare pediatric disease designation (RPDD) for the treatment of pediatric patients with acute myeloid leukemia (AML).
• SLS009 is a highly selective CDK9 inhibitor that has previously been granted orphan drug and fast track designations from the FDA for this indication.
• This marks the second RPDD to be granted to SLS009, following its designation in acute lymphoblastic leukemia (ALL) in June 2024.

The FDA has granted a RPDD to SLS009, a potentially first and best-in-class highly selective CDK9 inhibitor, for the potential treatment of pediatric AML.¹

“Receiving our second rare pediatric disease designation, following pediatric acute lymphoblastic leukemia last month, is another acknowledgment of SLS009’s novel transformational treatment potential to improve the lives of patients, including children with AML,” said Angelos Stergiou, MD, ScD h.c., president and chief executive officer of SELLAS, in a press release.

In March 2024, positive topline findings from the phase 2a portion of a phase 1/2 trial (NCT04588922) looking at SLS009 combined with azacitidine and venetoclax (Venclexta) showed that data cutoff date, the overall response rate (ORR) was 50% among patients with relapsed/refractory AML treated with the agent at the selected optimal dose of 30 mg twice weekly, exceeding the targeted 20% rate.²

Acute myeloid leukemia cells: © LASZLO - stock.adobe.com

The open-label, single-arm, multicenter trial is assessing SLS009 when given in combination with azacitidine and venetoclax in patients with AML that was relapsed/refractory to venetoclax-containing regimens. The primary end points are safety and tolerability, including incidence of dose-limiting toxicities (DLTs) and severity of all adverse effects. Secondary end points being evaluated include pharmacokinetics, complete response (CR), duration of response, progression-free survival, and overall survival (OS).

Additional study data revealed the ORR to be 10% among patients in the 45 mg cohort. In the 60 mg once a week cohort, the ORR was 20%. The 45 mg dose level was determined to be below the recommended phase 2 dose for use in the study.

The median OS was not yet reached at any dose level, and the target median OS is over 3 months. Strong antileukemic activity was seen, defined as bone marrow blast reduction of at least 50%, in about 67% of patients across all dose levels. Additionally, the first patient enrolled in the study who achieved a CR is still on the study and remains leukemia-free 9 months post enrollment.

For safety, SLS009 has a favorable safety profile across all dose levels. There were no DLTs observed at any of the dose levels, and no treatment-related toxicities deemed grade 3 or greater reported.

“This designation reinforces our dedication to addressing the urgent needs of children with AML, including those with treatment-resistant mutations, highlighting the promise of SLS009 to offer the specialized care and support they require, especially considering the limited treatment options for rare pediatric diseases. We look forward to continued SLS009 development and enrolling pediatric [patients with] AML in our phase 2 clinical trial,” added Stergiou.

Compared with other CDK9 inhibitors, SLS009 has reduced toxicity and increased potency. In patients with AML, data has shown SLS009 to demonstrate a high response rate, specifically among those with unfavorable prognostic factors like an ASXL1 mutation.

Most recently in June 2024, the FDA has granted a RPDD to SLS009 for treating pediatric patients with ALL. In October 2023, the FDA granted SLS009 an orphan drug designation for the treatment of relapsed/refractory AML, and in January 2024, the a fast track designation was granted by the FDA to SLS009 for this same indication.^3,4 Also in October 2023, SLS009 was granted an FDA fast track designation for the treatment of relapsed/refractory peripheral T-cell lymphoma.⁵

If the FDA approves a new drug application for SLS009 to treat pediatric AML in the future, SELLAS might receive a priority review voucher, which can be used for priority review of future applications or sold to other sponsors.

REFERENCES:

1. SELLAS announces U.S. FDA rare pediatric disease designation (RPDD) granted to SLS009 for the treatment of pediatric acute myeloid leukemia. News release. SELLAS Life Sciences Group, Inc. July 16, 2024. Accessed July 16, 2024. https://tinyurl.com/45sdx8vk

2. Sellas announces positive topline data from the phase 2a study of SLS009 in r/r AML and provides steering committee update on phase 3 REGAL study. News release. Sellas Life Sciences Group, Inc. March 26, 2024. Accessed July 16, 2024. https://tinyurl.com/3r6bjjhf

3. SELLAS receives FDA orphan drug designation for SLS009 for treatment of acute myeloid leukemia. News release. SELLAS Life Sciences. October 11, 2023. Accessed July 16, 2024. https://tinyurl.com/mvmfwydp

4. SELLAS Life Sciences receives FDA fast track designation for SLS009 for treatment of relapsed/refractory acute myeloid leukemia and provides updated data for phase 2a study of SLS009 in relapsed/refractory acute myeloid leukemia patients. News release. SELLAS Life Sciences. January 9, 2024. Accessed July 16, 2024. http://tinyurl.com/38rre4hh

5. SELLAS Life Sciences receives fast track designation from FDA for SLS009 for treatment of relapsed/refractory peripheral T-cell lymphomas. News release. SELLAS Life Sciences. October 30, 2023. Accessed July 16, 2024. https://tinyurl.com/4wt5tetn