This shows that TI with imetelstat treatment is achievable regardless of risk classification. The next abstract was accepted for poster presentation and examined the efficacy of imetelstat versus placebo across underlying mutations associated with MDS. Results show consistent TI responses in imetelstat treated patients across different molecularly defined subgroups, regardless of the presence of mutations associated with poor prognosis, including ASXL-1 or TP53, or the number of mutations. For example, the eight-week TI rate for patients who had three or more mutations, a group with known poor outcomes was 56% with imetelstat, and 14% with placebo. These results complement the data I just described for the IPSS-M classification, until we further believe support telomerase inhibition as a mechanism that can address the many different clones and causes of lower risk MDS.
The next abstract was also accepted for poster presentation and focuses on the patients who achieved continuous one year TI with imetelstat treatment, an unprecedented clinical outcome and lower risk MDS, which recapitulates what we saw in IMerge Phase 2. Among the nearly 20% of the imetelstat treated patients who achieved a one-year TI, the median duration of TI was over two years, and the median increase in hemoglobin was over five grams per deciliter. Of the 18 imetelstat treated one year TI responders with mutation data available, nearly three quarters achieved greater than 50% reduction in variant allele frequency, and importantly, nearly half experienced reduction of MDS associated mutations to an undetectable variant allele frequency.
We believe these cases of long-term uninterrupted TI accompanied by robust increases in hemoglobin and the elimination of MDS associated mutations suggest the potential of imetelstat to have disease modifying activity. The next abstract accepted for poster presentation summarizes results of Geron’s sponsored study in collaboration with the Moffitt Cancer Center. This population level analysis was based on the large U.S. healthcare insurance claims database that included over 5000 patients with lower risk MDS. This real-world data analysis showed durable transfusion independence after second line treatment is associated with improved survival. The median overall survival from the start of second line therapy was 23.4 months overall, and 37.9 months versus 9.3 months among 16-week TI responders versus non-responders.
This difference in OS was clinically and statistically significant, with a P value less than 0.001. For transfusion dependent patients’ achievement of TI with the second line treatment is associated with improved OS. Supporting the clinical benefit of TI and underscoring the importance of TI as a clinical trial primary endpoint. We look forward to all these presentations and discussions in San Diego this December. Turning now to our Phase 3 trial of imetelstat in relapsed refractory MF. Enrollment is progressing and we anticipate completing 50% enrollment by the end of this year. We continue to expect an interim analysis in the first half of 2025, which will occur when approximately 35% of the planned enrolled patients have died. A final analysis is expected in the first half of 2026, when over 50% of the planned enrolled patients have died.
We look forward to continuing to keep you updated on this important study. In addition to our Phase 3 programs, we are also evaluating imetelstat in a Phase 1 study as combination therapy with ruxolitinib in patients with frontline myelofibrosis. The study was informed by data from preclinical studies describing that the sequential treatment of ruxolitinib followed by imetelstat has a selective inhibitory effect on malignant myelofibrosis stem cells, while sparing normal hematopoietic stem cells. Our main goal for improved MF is to determine the safety profile of the combination regimen of ruxolitinib and imetelstat. And in addition, we plan to explore any potential activity in the frontline MF disease setting. Last month, the improved MF safety evaluation team or SET, which is comprised of study investigators evaluated patient data from the first cohort of patients, no dose limiting toxicities were identified, and the SET made a unanimous decision to escalate to the second dose cohort.
We are very pleased with this progress and look forward to providing future updates. With that, I’ll turn the call over to Anil for commercial update. Anil?
Anil Kapur: Thank you, Faye, and good morning, everyone. We have made significant progress regarding our commercial efforts in this quarter. We remain on track for launch readiness in the U.S. in early 2024 and are looking forward to the opportunity to bring this important new option to patients as they fight their disease. I’ll start by highlighting the recent updates to the NCCN treatment guidelines for MDS. This follows the recent FDA label expansion from this dataset in the frontline space. As you may be aware, the NCCN guidelines, along with publication of the results from randomized trials remain among the most important factors that influence clinical and fair pathways and significantly informed prescribing behavior. This next slide with a simplified schematic reflecting the revised NCCN guidelines shows that for the largest segment of the frontline RS negative patients, PSAs remain the preferred treatment for patients.
There also continues to be limited treatment options for patients with serum equal levels greater than 500 and participation in clinical trials is encouraged for those patients. Given these revised guidelines, we expect that the frontline lower risk MDS phase will evolve towards the use of both ESAs and this dataset. It is important to remember that the majority of the patients with symptomatic anemia are treated today with ESAs in the frontline setting and most will fail treatment in approximately two years. From our perspective, these updated guidelines reflect a lack of effective new treatment options. In particular, for the RS negative lower risk MDS patients who constitute 75% of the market, and for those whose serum equal levels are greater than 500.
This is a need we believe imetelstat can powerfully address and given the lack of effective treatment options, we expect imetelstat to be adopted for these patients for the treatment of lower risk MDS by the prescriber community. We believe that the low risk MDS market is right for a new, innovative and durable treatment that can be used broadly across MDS subtypes. We expect this large attractive market opportunity for imetelstat across three main patient segments across both the U.S. EU4 and U.K. highlighted on the right-hand side of the slide. These segments include frontline patients who are ESA ineligible, given their high baseline serum equal levels. ESA failed RS positive patients where there are limited treatment options including the luspatercept and HMAs. Lastly, there is also a very large segment of approximately 24,000 ESA failed RS negative patients who tend to have worse prognosis than RS positive patients and where there is a significant need for durable treatment.
