Thank you, Dinesh. Let's move to Slide 4. VERIFY is a global randomized, double-blind, placebo-controlled Phase III study investigating rusfertide versus placebo as an add-on therapy to current standard of care, which is also referred to as best available therapy in patients with PV. The key takeaways from the study are that VERIFY met the prespecified primary and all 4 key secondary endpoints centered around efficacy or clinical response and symptom improvements based on patient-reported outcome measures.
In addition, we confirmed that rusfertide was generally well-tolerated and that safety results were consistent with previous studies with no new safety signals identified. With respect to patient-reported outcomes, also referred to as PROs, rusfertide led to statistically significant improvements in PRO measures, specifically the PROMIS Fatigue and MFSAF questionnaires. These outstanding results support our planned regulatory filing in the U.S. in the fourth quarter of this year with our corporate partner, Takeda.
Next slide is the trial design. 293 patients with phlebotomy-dependent PV were enrolled across 19 countries and were randomized on a one-to-one basis to receive once weekly self-administered rusfertide or placebo at the outset with or without a stable dose of cytoreductive therapy. The inclusion criteria for VERIFY were quite similar to the revised Phase II study, which required that either low or high-risk PV patients be phlebotomy-dependent over the previous 28 weeks.
We define phlebotomy-dependent as having received at least 3 phlebotomies over the previous 28 weeks of 5 phlebotomies over the previous year. This requirement for frequent phlebotomy indicates that their PV and hematocrit levels were not adequately controlled with the current standard of care treatments, which could include stable doses of cytoreductive agents.
All patients were required to undergo phlebotomy to have a hematocrit less than 45% before randomization to establish a uniform baseline hematocrit to facilitate comparison between the rusfertide and placebo arms. Patients were stratified by cytoreductive therapy and the first 20 weeks of the study following randomization was a dose titration period, followed by the main efficacy evaluation period from week 20 to week 32, the 12-week period during which the primary endpoint for U.S. FDA approval was evaluated.
After week 32, all patients were eligible to receive open-label treatment with rusfertide plus the current standard of care in Part 1B, weeks 32 to 52. Patients who completed Part 1B were eligible to continue receiving rusfertide in Part 2 for 2 additional years. And as such, the study is ongoing. In the next slide, we examine the baseline demographics. As we -- as seen here, demographics and baseline disease characteristics were well balanced between the 2 treatment groups and VERIFY.
The median age was 57 years, with 46.4% of patients having high-risk disease defined either as age greater than or equal to 60 and/or prior thromboembolic event. With respect to phlebotomy history, the mean number of prior phlebotomies in the 28 weeks prior to study treatment was 4 and similar in both treatment arms. But the rusfertide plus current standard of care arm had double the number of patients requiring at least 7 therapeutic phlebotomies in the 28 weeks prior to study treatment.
So the rusfertide treated arm may have had more patients with difficult-to-treat PV. Rigorous prescreening of potential trial participants identified unknown cancers and ensured patients were on a stable therapeutic regimen prior to enrollment. At baseline, 130 patients or 44.4% were receiving phlebotomy alone without concurrent cytoreductive therapy. When we look at the patients receiving concurrent cytoreductive therapies, we see similar rates of hydroxyurea, interferon, JAK inhibitor in both treatment groups.
These rates of usage are in line with the overall PV population and speak to the generalizable or real-world nature of the VERIFY trial outcomes. Next slide, we will discuss the primary endpoint. The primary endpoint of the study was the proportion of patients in each arm demonstrating a clinical response. Three criteria were required to meet the definition of clinical response. First criterion is the absence of phlebotomy eligibility during week 20 to 32.
Phlebotomy eligibility is determined by an established algorithm based on hematocrit levels, which has been used in other trials in PV. The second criterion is no phlebotomy treatment during weeks 20 to 32. And the third criterion is that patients must complete all 32 weeks of treatment during Part 1A of the study. The primary endpoint of the study was met, showing that 37% of rusfertide plus current standard of care patients qualified as clinical responders compared to only 33% of the placebo plus current standard of care patients.
The P-value for this outcome was highly statistically significant at less than 0.0001. These compelling results are demonstrated on the bar graph on this slide. I would like to briefly comment on the 33% placebo response rate, which is noticeably higher than the placebo rates observed in the Phase III REVIVE study. To some extent, this is the typical shift you may see from a small U.S.-centric Phase II study to a broader, larger Phase III global study.
Based on differences in size and geography, we would expect a more heterogeneous patient population in the Phase III VERIFY study, including patients earlier in the disease journey, where some were heavily dependent on phlebotomy and required many phlebotomies to reach a hematocrit less than 45. However, once a hematocrit less than 45 was reached, the rate of subsequent treatments may not need to be as frequent.
Additionally, patients enrolled in VERIFY were required to complete all of Part 1A prior to transitioning to open-label rusfertide. In contrast, in REVIVE patients who discontinued treatment during the randomization period become a non-responder and still go on to open-label rusfertide. So this difference in trial design could also have attributed to a lower rate of non-responders in VERIFY. However, what is important to highlight is the magnitude of treatment effect between rusfertide and placebo is very similar in REVIVE and VERIFY studies, confirming rusfertide's efficacy.
The difference in response rate between the 2 arms is robust 44%, and it might actually suggest that rusfertide is a potential early treatment option for patients with less advanced disease. As a reminder, the VERIFY study remains ongoing and patients are continuing on Part 1B where placebo patients are crossed over to rusfertide treatment followed by a 2-year open-label extension of the study. In the next slide, you will see a forest plot that contains very important information.
When we look at the magnitude of treatment effect across key subgroups, we found that the strong statistically significant benefit with rusfertide plus the current standard of care in the primary outcome is also preserved across subgroups, including PV low and high-risk groups, geographic region and the use of concurrent cytoreductive therapy. On this slide, the benefit of rusfertide plus current standard of care is identified as the horizontal bars to the right of the vertical divider line.
And all subgroups analyzed show a significant improvement in the primary endpoint, the proportion of responders in favor of the rusfertide treated arm. Next slide; VERIFY has 4 key secondary endpoints that are a combination of efficacy assessment and patient-reported outcomes. Let's move to the first key secondary endpoint, which is a comparison of mean number of phlebotomies over the entire 32-week period between the 2 arms of the study.
The secondary endpoint is particularly important because it is the prespecified endpoint required for European regulatory filings. This key secondary endpoint was also met with a highly statistically significant p-value of less than 0.0001 with a mean of 0.5 versus 1.8 phlebotomies per patient in the rusfertide plus current standard of care group versus placebo plus standard of care arm during the entire 32-week period.
This reduction in therapeutic phlebotomies is similar to that found in the Phase II REVIVE study. Additionally, although not a formal endpoint, we are particularly impressed to see that 73% of patients in rusfertide arm received zero phlebotomies over the entire 32-week treatment period compared to only 22% of patients in the placebo arm.
And in the next slide, when we look at the different or the risk differential across key secondary subgroups, we find that the strong statistical significant benefit around rusfertide with the current standard of care in the first key secondary endpoint is also preserved across subgroups, including PV risk category, geographic region and the use of cytoreductive therapy. Next slide; the next key secondary endpoint we will discuss is hematocrit control or the proportion of patients with a hematocrit below 45% during week zero to week 32.
Rusfertide plus best available current standard of care was highly effective in controlling hematocrit with a highly statistically significant p-value of less than 0.0001. As seen on this graph, rusfertide consistently controls hematocrit from baseline to week 32. This dynamic is also specifically highlighted after week 32 when the placebo plus current standard of group transitions to rusfertide with the added benefit of phlebotomy at 32 weeks.
Overall, data demonstrates that rusfertide can be quickly titrated to an effective dose that controls hematocrit below the threshold of 45% and eliminates the need for phlebotomy. The rapid onset of action has also been observed in our earlier rusfertide studies in healthy volunteers and patients with PV. In the next slide, we will move on to patient-reported outcomes.
Initially, we focused primarily on hematocrit phlebotomy-based outcomes, but now we will focus on patient-reported outcomes or PROs, that assess patient symptomatology and give insight into the improvement in quality of life, which is, in our opinion, just as important as the clinical outcomes. Two key secondary outcomes looking at PRO in the study incorporated 2 validated assessments, the PROMIS Fatigue questionnaire that measures patient-reported symptoms of fatigue and their impact on how a patient feels and functions.
And secondly, the Myelofibrosis Symptom Assessment Form, also known as MFSAF. The MFSAF is a questionnaire that measures patient reporting of 7 key symptoms related to myelofibrosis, some of which are common among PV patients. The symptoms assessed by the MFSAF include itching, fatigue, night sweats and pain, among others, as seen on this slide. It is important to note that our selection of these PRO questionnaires and other overall PRO strategy was discussed and vetted with the FDA prior to trial initiation.
In the next slide, now we are looking at the first PRO secondary measure, a change in fatigue as assessed by the PROMIS Fatigue Short Form 8a. There was a statistically significant difference that reflected an improvement in fatigue of rusfertide plus best available current standard of care versus placebo plus best available current standard of care in VERIFY with a p-value of 0.03 in this PRO at week 32, using a least-squared means difference analysis, which involved modeling of covariants to ensure balance of treatment across potential imbalances. It was part of the pre-specified statistical analysis plan.
The next slide provides a little bit more detail. This fatigue questionnaire contains 8 questions asking about the effect of a specific treatment on differential aspects of fatigue. Individual question scores report the level of fatigue and the impact it has had on various activities and quality of life and range between 1, which is non-experienced and 5, which means always experienced, used to generate a raw score, which is then converted to a T-score.
We look forward to presenting additional data on this PRO at future medical meetings, including additional exploratory endpoints. Next, we will review the second PRO secondary outcome, improvement in symptoms as reported by a change in the MFSAF TSS7 questionnaire. We found a statistically significant difference using the MFSAF that reflected an improvement in symptomatology with rusfertide plus the current standard of care versus placebo plus current standard of care in VERIFY with a p-value of 0.24 at week 32, again, using a least-squared means difference analysis, which involved modeling covariants and baseline adjustments.
These MFSAF results confirm the data from the open-label Phase II results from REVIVE, where the MPN-SAF was used to assess symptomatology. Next slide provides more details. This MFSAF contains questions about 7 individual symptoms common in myelofibrosis, including fatigue, night sweats, itching, abdominal discomfort, pain under ribs on the left side, early satiety and bone pain. Each question about the symptom is scored between zero which means absent or 10, which means worst imaginable for each individual symptom with a total score out of 70.
Unlike PROMIS Fatigue instrument, raw data are used to score the MFSAF and to our knowledge, no other randomized Phase III trial in PV has shown a statistical improvement in symptomatology using these PRO instruments. As with the PROMIS Fatigue results, we look forward to presenting more detailed information at an upcoming medical meeting. On the next slide, we will discuss safety. On the safety side, we're extremely pleased with the overall profile observed in the study.
As you can see on this slide, rusfertide was generally well-tolerated in the Phase III VERIFY study and safety was in line with what has been reported in other rusfertide clinical studies. A majority of rusfertide-related adverse events were Grade 1 or 2 injection site reactions. Grade 1 [indiscernible] is known to be associated with rusfertide's mechanism of action due to the reduction in the production of red blood cells. No new safety findings were observed in this study.
No serious adverse events or SAEs were attributed to rusfertide. Next slide; as we have previously discussed in the VERIFY top line conference call in March, non-PV cancers are observed in patients with PV, including skin malignancies at a higher rate than in the general population. It is not clear whether this risk is due to the PV itself or prior therapies such as hydroxyurea. Given this risk, we instituted [indiscernible] and identified 10 skin malignancies, including one malignant melanoma prior to randomization.
We also identified multiple premalignant lesions such as actinic keratosis and dysplastic nevi. During the first 32 weeks of VERIFY, 8 other cancers were identified with 7 being in the placebo plus current standard of care arm and only one in the rusfertide plus current standard of care arm, indicating that there is no evidence of an increased risk of cancer in rusfertide-treated patients compared to those on placebo during this 32-week period. However, the rate of serious -- moreover, the rate of serious adverse events in the first 32 weeks of VERIFY showed 3.4% in the rusfertide plus current standard of care and 4.8% in the placebo plus current standard of care.
So overall, we found a non-statistically significant imbalance in favor of rusfertide treatment arm for both secondary cancers and SAEs. Next slide; in conclusion, VERIFY is a strongly positive study that met statistical significance in its primary endpoint and all 4 key secondary endpoints. In phlebotomy-dependent PV patients receiving the best available current standard of care treatment, the addition of rusfertide reduced the mean number of phlebotomies, improved hematocrit control and improved symptoms compared to placebo plus best available current standard of care.
We believe rusfertide is the first therapeutic to prospectively demonstrate a statistically significant improvement in PROs using PROMIS Fatigue and MFSAF questionnaires in patients with PV. Moreover, rusfertide had a safety and tolerability profile consistent with prior studies, and there were no new safety signals. Overall, we believe this is the best possible outcome for the Phase III VERIFY trial.
We are thrilled with this outstanding results. Rusfertide continues to produce data supporting its first-in-class nature. Because its efficacy is rapid, consistent and durable, rusfertide has the potential to fulfill unmet needs for patients with PV who are already receiving best available standard of care and yet achieving adequate hematocrit or symptom control.
With that, I will pass it back to Dinesh.
