EVOLVE-MS-2: GI Tolerability Outcomes Were Assessed in Patients With RRMS Taking VUMERITY vs Patients Taking dimethyl fumarate1,2

Study design

  • EVOLVE-MS-2 was a phase 3, randomized, head-to-head, active-controlled, 5-week study to evaluate patient-assessed GI tolerability of VUMERITY versus dimethyl fumarate in patients with RRMS
  • The EVOLVE-MS-2 study used an adaptive trial design in which data from Part A were used to evaluate the utility of GI symptom scales and to inform the GI tolerability endpoints and sample size for Part B
  • Parts A and B were identical in study assessments. Following the completion of Part A, a planned, unblinded analysis of GI tolerability was performed to refine the primary endpoint to reflect the most sensitive measure for detecting a difference between VUMERITY and dimethyl fumarate and re-estimate sample size
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Patients who completed EVOLVE-MS-2 could roll over into a 96-week open-label study

*In study week 1, the titrated dose for VUMERITY was one 231 mg delayed-release capsule taken orally, twice daily. The titrated dose for dimethyl fumarate was one 120 mg delayed-release capsule taken orally, twice daily. From study weeks 2–5, the full dose for VUMERITY was two 231 mg delayed-release capsules taken orally, twice daily, and the full dose for dimethyl fumarate was one 240 mg delayed-release capsule taken orally, twice daily.

Limitations and disclosures

  • The GI symptom intensity scales are not validated
  • Results should be interpreted with caution due to the 5-week duration
  • Patients were excluded if they had a history of GI surgery, clinically significant recurring or active GI symptoms within
    3 months of screening, or chronic use of medical therapy to treat GI symptoms within 1 month of screening
  • The results from this study are not included in the full Prescribing Information for VUMERITY. The US Food and Drug Administration did not consider the results of this study when approving VUMERITY

Key eligibility criteria

  • Patients aged 18–65 years with a confirmed RRMS diagnosis
  • Patients had no history of GI surgery, clinically significant recurring or active GI symptoms within 3 months of screening, or chronic use of medical therapy to treat GI symptoms within 1 month of screening

GI tolerability assessments

  • Patients used 2 GI tolerability scales to self-assess the duration and severity of their GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea) on an 11-point patient-reported numerical rating scale using eDiaries
    • Individual Gastrointestinal Symptom and Impact Scale (IGISIS): patients self-assessed the intensity of each of the 5 GI symptoms twice daily, within 9 hours of taking each dose
    • Global Gastrointestinal Symptom and Impact Scale (GGISIS): patients self-assessed the intensity of any GI symptoms over the last 24 hours

Primary endpoint

  • Number of days (relative to exposure) with any individual GI symptom intensity score ≥2 in the overall population

Secondary endpoints

Secondary endpoints were assessed in this study, but results are not presented here.

 

  • Number of days (relative to exposure) with individual GI symptom intensity scores of ≥1 or ≥3 in the overall population
  • Number of days (relative to exposure) with an individual GI symptom intensity score of ≥2 in patients from Part B only
  • Number of days (relative to exposure) with global GI symptom intensity scores of ≥1, ≥2, or ≥3 in the overall population
  • Worst individual GI symptom score by study week

Patients self-reported 46% fewer days with GI symptoms on VUMERITY vs dimethyl fumarate

Primary endpoint

Based on Part A and Part B

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Over a 5-week treatment period, VUMERITY showed a 46% reduction (P=0.0003) in the number of days (adjusted rate ratio, 0.54 [95% CI, 0.39-0.75]) patients experienced a GI symptom intensity score rated ≥2 on an Individual GI Symptom and Impact Scale (a 0- to 10-point scale)

Overall, 19.3% (17/88) of patients in the VUMERITY group and 30.6% (37/121) of patients in the DMF group used concomitant medications to treat GI-related AEs during the treatment period

  • These days are not consecutive

Intensity of nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea reported twice per day.

Patients completed ≥1 postbaseline tolerability eDiary assessment and were included in the analysis of patient-assessed GI tolerability.

0.8% of patients taking VUMERITY discontinued due to GI AEs, compared with 4.8% of those taking dimethyl fumarate

Disposition of Patients With RRMS in EVOLVE-MS-2

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GI AEs Experienced in ≥5% of Patients in Either Group

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§VUMERITY, n=253; DMF, n=249.