FDA Grants Orphan Drug Status to SEL120 for Acute Myeloid Leukemia

FDA Grants Orphan Drug Status to SEL120 for Acute Myeloid Leukemia

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Ryvu Therapeutics’ oral inhibitor SEL120 for treating people with acute myeloid leukemia (AML).

In the U.S., orphan drug designation is given to medicines with potential to be safe and effective treatments for rare conditions affecting no more than 200,000 people. It is expected to provide regulatory support and financial benefits to help accelerate the clinical development of SEL120, and to guarantee a seven-year period of marketing exclusivity if granted regulatory approval.

“The FDA’s granting orphan drug designation to SEL120, is a significant encouragement for advancement of our clinical strategic plan addressing the unmet medical needs in the area of AML treatment, a disease where patients still face poor prognosis,” Setareh Shamsili, MD, PhD, said in a press release. Shamsili is chief medical officer and executive vice president at Ryvu Therapeutics.

SEL120 is a small molecule developed with support from The Leukemia & Lymphoma Society Therapy Acceleration Program, an initiative that seeks to speed the development of promising new therapies for blood cancers such as AML.

It works by selectively targeting CDK8 and its structurally similar protein CDK19, which are part of a protein complex involved in gene expression — the process by which genes give rise to proteins — controlling a series of genes involved in cancer pathways.

Preclinical studies have demonstrated that blocking CDK8 and CDK19 using SEL120 represses cancer signaling in AML cells, making them either enter a process of programmed cell death or differentiate into a more mature state that prevents them from replicating uncontrollably.

In animal models, SEL120 induced complete regression of AML, and studies suggest it can be used in combination with standard-of-care medications for AML.

An ongoing Phase 1b clinical trial (NCT04021368) is investigating SEL120 in AML patients and in people with high-risk myelodysplastic syndrome (MDS), a rare type of blood cancer, who have received one to three prior lines of therapy.

Currently recruiting, the first-in-human trial aims to include 68 participants at six U.S. sites, who will receive a total of seven oral doses of SEL120 in a three-week treatment cycle. In a first part, participants will be treated with escalating doses of SEL120 to determine the safest and most effective dose for continued testing.

Then, an additional six to 20 patients will receive the established dose to continue assessing its safety and effectiveness in AML and MDS. The study also will assess SEL120’s pharmacokinetic (how it behaves inside the body in terms of absorption, distribution, metabolism, and excretion) and pharmacodynamics (which studies the effects of SEL120 in the body).

Top-line results are expected by the end of this year.

“SEL120 has shown strong proof of concept in the preclinical studies and has received a strategic support from The Leukemia & Lymphoma Society (LLS) through its Therapy Acceleration Program (TAP),” Shamsili said.

“SEL120 may have the potential to offer an important therapeutic benefit in AML and in particular to those refractory/relapsed AML patients with the poorest prognosis, worldwide,” she added.