MIMRYLO™ (rusfertide) reduced phlebotomies, maintained HCT control below 45%, and reduced fatigue1

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MIMRYLO was studied in VERIFY, the largest pivotal trial in PV1-3

Trial Design

VERIFY was a multicenter, randomized, double-blind, placebo-controlled phase 3 trial of 293 adult patients with PV, in which MIMRYLO was studied both alone and as a combination therapy

VERIFY trial design1,4

VERIFY trial design: 293 patients randomized 1:1 to MIMRYLO plus current treatment (n=147) or placebo plus current treatment (n=146) for Weeks 0-32, followed by open-label MIMRYLO from Week 32 through end of trial, spanning Part 1a through Part 3.
  • The primary endpoint was the proportion of patients achieving phlebotomy ineligibility response between Weeks 20-321
  • Key secondary endpoints included1:
    • Mean number of phlebotomies (Baseline-Week 32)
    • Proportion of patients who had HCT values <45% for the whole trial (Weeks 0-32)
    • Mean change in total fatigue score based on PROMIS Fatigue Short Form 8a (Baseline-Week 32)
*Both arms of the trial were studied with phlebotomy rescue, with or without CRT (hydroxyurea, interferon, ruxolitinib).1
†A response was defined as the absence of phlebotomy eligibility, which was defined as a confirmed HCT ≥45% that is at least 3 percentage (absolute) points higher than the HCT obtained at baseline or an HCT ≥48%.1
VERIFY trial baseline characteristics

Baseline characteristics

Eligible patients in the VERIFY trial required phlebotomies due to inadequate HCT control while receiving their ongoing current treatment, phlebotomy rescue, with or without CRT.1,4
Baseline characteristics: 45% (n=131) phlebotomy only, 39% (n=114) phlebotomy plus hydroxyurea, 13% (n=39) phlebotomy plus interferon, 2% (n=7) phlebotomy plus ruxolitinib, 1% (n=2) phlebotomy plus combination cytoreductive therapy; mean age 57 years (range 27-86); 105 US vs 188 other-region patients; 73% (n=214) men, 27% (n=79) women; 53% (n=156) low risk, 47% (n=137) high risk.
Eligibility criteria1,4
  • Adults (≥18 years of age) who met the revised 2016 World Health Organization criteria for the diagnosis of PV
  • Had phlebotomy-dependent disease due to inadequate HCT control (defined as ≥3 phlebotomies within 28 weeks or ≥5 within 1 year required prior to randomization)
  • HCT <45% immediately before randomization
*Low risk is defined as age less than 60 years and no history of previous TE(s).1
†High risk is defined as age greater than or equal to 60 years, and/or a history of previous TE(s).1
Primary Endpoint

More patients taking MIMRYLO maintained HCT levels without requiring phlebotomies vs the control arm

Proportion of patients achieving phlebotomy ineligibility response from Weeks 20-321

Primary endpoint: 77% of patients on MIMRYLO (113 of 147) achieved phlebotomy ineligibility response from Weeks 20-32, versus 33% on control arm (48 of 146).
A response was defined as absence of phlebotomy eligibility, meaning either a confirmed HCT ≥45% that is at least 3 percentage (absolute) points higher than the HCT obtained at baseline, or HCT ≥48%1
*Both arms of the trial were studied with phlebotomy rescue, with or without CRT (hydroxyurea, interferon, ruxolitinib).1
†P-value is obtained from the Cochran-Mantel-Haenszel test stratifying by ongoing therapy.1
Secondary Endpoints

MIMRYLO met key secondary endpoints

MIMRYLO reduced phlebotomies, maintained HCT levels <45%, and reduced fatigue vs the control arm1

MIMRYLO was proven to:

Reduce the need for rescue phlebotomies

Mean number of phlebotomies (Baseline-Week 32)

MIMRYLO was proven to reduce the need for rescue phlebotomies

Over the 32-week double-blind portion of the trial:
Patients had significantly fewer phlebotomies with MIMRYLO compared to the control arm1

Mean number of phlebotomies1

Mean number of phlebotomies from baseline to Week 32: 0.5 per patient with MIMRYLO versus 1.8 per patient with control arm, a 3-times reduction.
*Both arms of the trial were studied with phlebotomy rescue, with or without CRT (hydroxyurea, interferon, ruxolitinib).1
†LSMs, 95% CI, and p-value are obtained from ANCOVA model adjusted for pre-treatment number of phlebotomies, treatment, and stratification variable (ongoing therapy).1
Keep HCT below 45%

Proportion of patients who had HCT values <45% (Weeks 0-32)

MIMRYLO was proven to keep HCT below 45%

Over the 32-week double-blind portion of the trial:
A significantly larger proportion of patients on MIMRYLO maintained HCT below 45% compared to the control arm1

Proportion of patients maintaining HCT values <45%1*

Proportion of patients with all HCT values below 45% from Weeks 0-32: 63% with MIMRYLO (92 of 147) versus 14% with control arm (21 of 146).
*A single HCT ≥45% was permitted.1
†Both arms of the trial were studied with phlebotomy rescue, with or without CRT (hydroxyurea, interferon, ruxolitinib).1
‡P-value is obtained from the Cochran-Mantel-Haenszel test stratifying by ongoing therapy.1
Reduce fatigue

Change in fatigue score based on PROMIS Short Form 8a (Baseline-Week 32)

MIMRYLO was proven to reduce fatigue

At Week 32 of the double-blind portion of the trial, measured by the PROMIS Fatigue Short Form 8a T-score*:
Patients taking MIMRYLO saw a statistically significant improvement in fatigue vs the control arm1

LSM Difference from baseline total fatigue score1

MIMRYLO LSM change -1.8 vs control arm 0.2, fatigue score, Week 32

At Week 32 of the double-blind portion of the trial, measured by the PROMIS Fatigue Short Form 8a T-score*:
Patients taking MIMRYLO reported meaningful within-person improvement in fatigue vs the control arm4

Proportion of patients with meaningful within-person change4

27% MIMRYLO vs 16% control improved fatigue (ITT); 42% vs 14% in moderate/severe patients

VERIFY was not designed to detect a statistically significant difference between arms for within-person change in PROMIS Fatigue Short Form 8a PROs.4

In the pivotal trial, fatigue was assessed as a key secondary endpoint using the PROMIS T-score, a validated PRO measure. PROMIS Fatigue scores reflect the severity and impact of fatigue from the patient's perspective. PROMIS Fatigue Short Form 8a assesses fatigue severity over the prior 7 days using patient-reported ratings that are converted to a standardized T-score (mean=50, SD=10); lower scores indicate less fatigue. Values shown represent an LSM change from baseline.1,4,5

*For the PROMIS T-score, Week 32 change from baseline is available for 120 patients in the MIMRYLO arm and 115 patients in the control arm.1
†Both arms of the trial were studied with phlebotomy rescue, with or without CRT (hydroxyurea, interferon, ruxolitnib).1
‡LSMs, 95% CI, and p-value are obtained from MMRM model adjusted for baseline, treatment, visit, treatment by visit interaction, baseline by visit interaction, and stratification variable (ongoing therapy).1
§For the PROMIS Fatigue Short Form 8a, patients with a T-score ≥58.8 based on the severity cutoff were classified as having moderate or severe symptoms at baseline.4  
∥P-value is obtained from the Cochran-Mantel-Haenszel test stratifying by ongoing therapy.4

Open-label Treatment Extension

MIMRYLO delivered sustained HCT control <45% up to Week 52

Of the 113 patients in the MIMRYLO arm who achieved primary endpoint response during Weeks 20-32, 84% (n=95) maintained their response out to Week 524*

HCT levels over 52 weeks4

Line graph of mean HCT value change from baseline over 52 weeks: MIMRYLO arm stayed near zero throughout, control arm rose above 2 percentage points by Week 32, then dropped sharply after crossover to MIMRYLO and remained low through Week 52.
Patients were randomized 1:1 to the MIMRYLO or control arm, which included their current treatment.* Patients that completed 32 weeks of treatment were eligible to receive open-label treatment with MIMRYLO until Week 52.4

Patients receiving MIMRYLO demonstrated sustained or reduced HCT levels from baseline during Weeks 0-324

Patients who switched from the control arm to MIMRYLO showed reduced HCT levels within 4 weeks of the first dose4
*Both arms of the trial were studied with phlebotomy rescue, with or without CRT (hydroxyurea, interferon, ruxolitinib).1
Individual phlebotomy results out to Week 52

MIMRYLO reduced the need for rescue phlebotomies

Treatment with MIMRYLO over 52 weeks was associated with a marked reduction in phlebotomies and phlebotomy eligibility compared to the 52-week period before treatment4

Individual patient phlebotomy results over 52 weeks in the MIMRYLO arm4*

Swimlane chart of individual patient phlebotomy events over 52 weeks in the MIMRYLO arm, showing markedly fewer rescue phlebotomies after treatment start compared to the pre-enrollment period.

Individual patient phlebotomy results over 52 weeks in the control arm4*

Swimlane chart of individual patient phlebotomy events over 52 weeks in the control arm, showing continued frequent rescue phlebotomies and phlebotomy eligibility during the 32-week placebo period, followed by markedly fewer events after patients crossed over to open-label MIMRYLO at Week 32.

Each row represents an individual patient. Unique markers indicate rescue phlebotomies.

At Week 32, patients in the control arm entered the open-label extension with MIMRYLO.1

This trial was not powered to show a statistically significant difference in response vs the control arm as measured by reduction in phlebotomy burden.4

*Both arms of the trial were studied with phlebotomy rescue, with or without CRT (hydroxyurea, interferon, ruxolitinib).1

Iron Data

MIMRYLO helped patients with low ferritin achieve normal levels over time

From Weeks 0-32, 61% (n=74) of patients taking MIMRYLO increased ferritin levels from low to normal vs 12% (n=15) in the control arm4

Ferritin levels over 52 weeks4

Line graph of ferritin levels over 60 weeks: MIMRYLO arm rose from about 20 to over 170 µg/L, control arm remained flat near 20 µg/L until crossover to MIMRYLO at Week 32, then rose to about 130 µg/L by Week 60.
Ferritin is an indicator of the body's iron stores. Normal ranges for men are between 15-200 μg/L and 15-150 μg/L for women. Over the 32-week double-blind portion of the trial, MIMRYLO patients saw mean ferritin concentrations increase from 21 µg/L at baseline to 124 µg/L vs the control arm, which was relatively unchanged from 19 µg/L to 20 µg/L. At Week 52 for patients randomized to receive MIMRYLO, ferritin concentrations increased to 174 μg/L.1,4
*Both arms of the trial were studied with phlebotomy rescue, with or without CRT (hydroxyurea, interferon, ruxolitinib).1

ANCOVA=analysis of covariance; CI=confidence interval; CRT=cytoreductive therapy; CT=current treatment; EOT=end of trial; HCT=hematocrit; ITT=intent-to-treat; LSM=least-squares mean; MMRM=Mixed models for repeated measures; PRO=patient-reported outcome; PROMIS=Patient-Reported Outcomes Measurement Information System; PV=polycythemia vera; SD=standard deviation; SE=standard error; TE=thrombotic event.

IMPORTANT SAFETY INFORMATION AND INDICATION

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