BAFIERTAM Delivers a Well-
BAFIERTAM is proven to be safe and
effective for your
patients with relapsing MS.
Multiple clinical trials demonstrated an established safety profile
The data shown below were obtained using dimethyl fumarate (the prodrug of BAFIERTAM® [monomethyl fumarate]) delayed-release capsules. The adverse reactions in the DEFINE and CONFIRM studies were based on safety information from 769 patients treated with DMF 240 mg twice a day and 771 placebo-treated patients.2
The most common adverse reactions for DMF were flushing, abdominal pain, diarrhea, and nausea.
Adverse reactions in DEFINE and CONFIRM studies reported for DMF 240 mg BID at ≥2% higher incidence than placebo2
- DMF caused GI events (eg, nausea, vomiting, diarrhea, abdominal pain, and dyspepsia)
- In clinical trials, the incidence of GI events was higher early in the course of treatment (primarily during the first month) and usually decreased over time in patients treated with DMF compared with placebo
- 4% of patients treated with DMF and <1% of patients on placebo discontinued due to GI events
- The incidence of serious GI events was 1% in patients treated with DMF
- An increased incidence of elevations of hepatic transaminases in patients treated with DMF in clinical trials was seen primarily during the first 6 months of treatment, and most patients with elevations had levels <3 times the upper limit of normal (ULN)
- Elevations of alanine aminotransferase and aspartate aminotransferase to ≥3 times the ULN occurred in a small number of patients treated with DMF and in patients on placebo and were balanced between the groups
- There were no elevations in transaminases ≥3 times the ULN with concomitant elevations in total bilirubin >2 times the ULN
- Discontinuations due to elevated hepatic transaminases were <1% and were similar in patients treated with DMF or placebo
- A transient increase in mean eosinophil counts was seen during the first 2 months of therapy with DMF
Adverse reactions in studies with BAFIERTAM
In clinical studies, a total of 178 healthy subjects received single doses of BAFIERTAM. The adverse reaction profile of BAFIERTAM was consistent with the experience in the placebo-controlled clinical trials with DMF.
BAFIERTAM can be taken with
or without food
Additional data on GI tolerability from BLS-11-1096
GI tolerability outcomes assessed in healthy subjects taking BAFIERTAM vs healthy subjects taking BAFIERTAM prodrug dimethyl fumarate (Tecfidera®)
- The study was designed to evaluate bioequivalent doses of MMF vs DMF, starting with a 1-week titration phase of MMF 95 mg vs DMF 120 mg, administered twice daily, followed by a 4-week maintenance phase of MMF 190 mg vs DMF 240 mg, administered twice daily*
- Subjects were randomized 1:1 into one of the treatment groups. Because multiple sclerosis is more common in women than in men, randomization was stratified by gender (3:1, female:male)
The primary endpoint was the area under the curve (AUC) in each of the individual symptoms in the MOGISS over the 5-week treatment period
The other endpoints included the AUC over the 5-week treatment period in the MOGISS composite and total scores, duration and severity of GI events, number and percentage of subjects reporting GI events during the overall treatment period, and assessment of safety/tolerability
- Healthy male and nonpregnant female subjects aged 18 to 65 years
- Subjects had no clinically significant history or presence of any clinically significant GI pathology, unresolved GI symptoms, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug experienced within 7 days prior to administration of the first study drug
Subjects used a shortened version of the Modified Overall Gastrointestinal Symptom Scale (MOGISS) to self-assess and rate daily the severity of each symptom (abdominal pain [upper and lower], vomiting, diarrhea, nausea, flatulence, bloating, and constipation) on a scale of 0 (did not have) to 10 (extreme)
Limitations and disclosures
- The study did not meet its primary endpoint. Therefore, all analyses are exploratory, and statistics are descriptive
- The GI symptom intensity scales were not validated
- Results should be interpreted with caution because of the 5-week duration
- Subjects were excluded if they had a clinically significant history or presence of any clinically significant GI pathology, unresolved GI symptoms, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug experienced within 7 days prior to administration of the first study drug, as determined by the study investigator
- The results from this study are not included in the full Prescribing Information for BAFIERTAM. The US Food and Drug Administration did not consider the results of this study when approving BAFIERTAM
- The study was conducted in healthy subjects, not patients with MS
- The study was not powered to show a difference between BAFIERTAM and Tecfidera
Hierarchical, inferential analysis of the testing of overall treatment differences for the first primary endpoint, abdominal pain, or the other primary endpoints was not significantly different between treatments. Therefore, all analyses are exploratory, and statistics are descriptive.
GI symptom differences
Exploratory analyses of the Least Squares Mean AUC values for each GI symptom were consistently lower for BAFIERTAM than for Tecfidera, as shown in the figure below.
Comparison of MOGISS symptoms AUCs between treatments6
GI symptom severity
Inferential analysis of the hierarchical testing of overall treatment differences in each MOGISS symptom AUC occurred in the following sequence: (1) Abdominal pain, (2) Vomiting, (3) Diarrhea, (4) Nausea, (5) Flatulence, (6) Bloating, (7) Constipation. The first primary endpoint, Abdominal Pain, was not significantly different between treatments; thus, all subsequent statistical analyses in this hierarchical testing were exploratory. Although there were no statistically significant differences in any of the other primary endpoints between BAFIERTAM and Tecfidera, for each symptom, LSMean AUC values were lower for BAFIERTAM than Tecfidera.
Incidence of moderate to extreme worst MOGISS scores6
GI symptoms duration
Exploratory analyses of moderate to extreme GI events exhibited shorter mean duration of MOGISS during the treatment period for BAFIERTAM (mean: 4 days) than for Tecfidera (5 days) overall. The overall difference between treatments became statistically significant from week 3 onward, with shorter mean duration for BAFIERTAM (P=.042 to .009). In analogous analyses of each MOGISS symptom, diarrhea duration during the entire treatment period was statistically significantly lower for BAFIERTAM overall (P=.036).
There were no other statistically significant differences during the treatment period, by the study week, or by gender (p>0.060). None of the other comparisons reached statistical significance (p>0.056).
A total of 122 (58%) subjects reported AEs during the study
- 53% of BAFIERTAM-treated subjects vs 63% of Tecfidera-treated subjects (P=.202) reported AEs
- Mild flushing was the most reported AE by both groups, occurring in 43% and 54% of subjects on BAFIERTAM and DMF, respectively
- No subjects stopped treatment due to GI AEs
- The table summarizes reported GI AEs that were considered related to the study drug
Adapted from Table 4, Wynn publication