Geron's First Approved Drug: FDA Greenlights Rytelo for MDS

The U.S. Food and Drug Administration (FDA) has granted approval to Geron’s oligonucleotide telomerase inhibitor, Rytelo (imetelstat), for treating adults with transfusion-dependent lower-risk myelodysplastic syndromes (LR-MDS) who either cannot use erythropoiesis-stimulating agents (ESA) or have not responded adequately to them. This approval is a significant milestone for Geron, marking its first authorized product since its inception in 1990. Imetelstat began development in 2005.

John Scarlett, CEO of Geron, highlighted the potential benefits of the drug for LR-MDS patients, emphasizing that it could offer over 24 weeks of relief from red blood cell transfusions and symptomatic anemia. The FDA’s approval, which was announced before the anticipated Prescription Drug User Fee Act (PDUFA) date of June 16, caused a significant rise in the company’s shares, which surged by up to 23% on the day of the announcement.

The approval of Rytelo is supported by the results from the Phase III IMerge study. In this study, around 40% of patients who received Rytelo achieved the primary goal of independence from red-blood-cell transfusions (RBC-TI) for at least eight weeks, compared to only 15% of patients who received a placebo. The drug also showed a 28% response rate for RBC-TI at 24 weeks and 13.6% at one year, significantly higher than the 3.3% and 1.7% rates seen in the placebo group, respectively. From a safety perspective, the most common serious adverse events were thrombocytopenia and neutropenia, but these were generally transient and manageable.

However, there were regulatory concerns prior to an advisory committee (adcom) meeting on Rytelo. FDA staff questioned the clinical significance of the results, particularly the impact on overall survival or remission, and pointed out the higher incidence of serious adverse events in the Rytelo group (91%) compared to the placebo group (47%). Additionally, there were doubts about the relevance of the IMerge study findings to the U.S. population, since most participants were enrolled outside the country.

Despite these concerns, the FDA advisory committee voted 12-2 in favor of Rytelo, acknowledging its clinical benefit/risk profile. Those who opposed the recommendation argued that the therapy would benefit only a small fraction of patients and that the increased toxicity risks outweighed the benefits. Analysts from Stifel Nicolaus had estimated a 50/50 chance of Rytelo receiving a boxed warning for hematological toxicity but suggested this might not be necessary, as most patients returned to normal or near-normal neutrophil and platelet levels within three months, with no significant long-term effects.

Rytelo is set to compete with Bristol Myers Squibb’s Reblozyl (luspatercept-aamt), which was approved by the FDA in August. An expert interviewed by Firstword in March remarked that while Rytelo shows impressive potential in reducing transfusion needs, Reblozyl might surpass it in the treatment algorithm for MDS due to its lower risk of causing cytopenia.

Additionally, the Institute for Clinical and Economic Review (ICER) recently recommended that Rytelo’s annual cost should be around $119,000 to be considered cost-effective for MDS patients.