FDA Approves Geron’s Rytelo for Adults with Rare Blood Cancer

Rare Daily Staff

The U.S. Food and Drug Administration has approved Geron’s Rytelo to treat adult patients with lower risk myelodysplastic syndrome, a rare blood cancer.

The approval of Rytelo is specifically for adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent (TD) anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA).

“With the approval and availability of Rytelo, we believe eligible patients with lower-risk MDS can potentially experience meaningful clinical benefit, particularly the potential for greater than 24 weeks of freedom from the burden of red blood cell transfusions and symptomatic anemia,” said John Scarlett, Geron’s chairman and CEO.

Lower-risk myelodysplastic syndromes (LR-MDS) is a blood cancer that often progresses to require increasingly intensified management of key symptoms such as anemia and resulting fatigue. These symptomatic LR-MDS patients frequently become red blood cell transfusion dependent, which has been shown to be associated with short- and long-term clinical consequences that reduce quality of life and shorten survival. There is a high unmet need for many LR-MDS patients, particularly those with characteristics having poorer prognosis. Current treatment options for those failing ESA are limited to select sub-populations and there is an unmet need for treatments that can provide extended and continuous red blood cell transfusion independence.

Rytelo is a first-in-class oligonucleotide that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division.

The FDA approval of Rytelo is based on results from the IMerge phase 3 clinical trial, which met its primary and key secondary endpoints, with RYTELO demonstrating significantly higher rates of red blood cell transfusion independence (RBC-TI) versus placebo for at least eight consecutive weeks (Rytelo 39.8 percent; placebo 15.0 percent) and for at least 24 weeks (Rytelo 28.0 percent; placebo 3.3 percent). RBC-TI was durable and sustained in the Rytelo treated population, with a median RBC-TI duration for 8-week responders and 24-week responders of approximately 1 year and 1.5 years, respectively.

In an exploratory analysis of Rytelo -treated patients achieving ≥8-week RBC-TI, median increases in hemoglobin were 3.6 g/dL for Rytelo and 0.8 g/dL for placebo. Clinically meaningful efficacy results were observed across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category.

In the IMerge trial, the safety profile of Rytelo was well-characterized with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar side effects for hematologists who are experienced with managing cytopenias. The most common Grade 3/4 adverse reactions were neutropenia (72 percent) and thrombocytopenia (65 percent), which lasted a median duration of less than two weeks, and in more than 80 percent of patients were resolved to Grade < 2 in under four weeks. Cytopenias were generally manageable with dose modifications. The intravenous administration of Rytelo every four weeks aligns to routine blood count monitoring for these patients.

The most common adverse reactions (incidence ≥10 percent with a difference between arms of >5 percent compared to placebo), including laboratory abnormalities, were decreased platelets (thrombocytopenia), decreased white blood cells, decreased neutrophils (neutropenia), increased aspartate aminotransferase (AST), increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT), fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. Clinically relevant adverse reactions in < 5 percent of patients who received Rytelo included febrile neutropenia, sepsis, gastrointestinal hemorrhage, and hypertension.

“What is exciting about Rytelo is the totality of the clinical benefit across LR-MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias,” said Rami Komrokji, vice chair, Malignant Hematology Department, Moffitt Cancer Center, and an investigator of the pivotal IMerge clinical trial. “The treatment goal for patients with LR-MDS and anemia is transfusion-independence and before today, this wasn’t possible for many patients.”