Abstract
Background
Bafiertam® (monomethyl fumarate [MMF]) and Vumerity® (diroximel fumarate [DRF]) are
two FDA approved drug products for the treatment of relapsing forms of multiple sclerosis
(MS) to include clinically isolated syndrome, relapsing-remitting disease, and active
secondary progressive disease, in adults. Vumerity® is a prodrug of MMF which requires
enzymatic conversion of DRF to the active drug MMF, the moiety responsible for the
therapeutic efficacy; whereas Bafiertam® contains MMF, providing the active drug directly
without any need for enzymatic conversion.
Objective
The objective of this study was to evaluate the pharmacokinetics and relative bioavailability
of MMF from oral administration of two Bafiertam® capsules each containing 95 mg of
MMF in comparison to two Vumerity® capsules each containing 231 mg of DRF, the therapeutic
doses of each product.
Methods
This was a single-dose, open-label, randomized, 2-way crossover study evaluating two
treatments over two periods with a washout interval between treatments. Forty-four
healthy male or female subjects were planned to receive each of the two treatments
to assure 40 completed dosing: a single dose of 2 × 95 mg Bafiertam® capsules and
a single dose of 2 × 231 mg Vumerity® capsules under fasting conditions in a randomized
crossover fashion. Blood samples were obtained prior to dosing and at prespecified
time points through 24 h post-dose to determine plasma concentrations of MMF. MMF
pharmacokinetic [PK] parameters were calculated and included maximum observed concentration
(Cmax), time to reach Cmax (tmax), apparent half-life of MMF in plasma (t1/2), AUC0-t which is the area under the plasma concentration vs. time curve (AUC) from time zero
(dosing time) to the last time point, t, with quantifiable MMF concentration, and
AUC0-inf which is AUC0-t plus the extrapolated AUC from time t to infinity.
Results
Forty-one subjects completed the study as planned. MMF in Bafiertam® capsules was
well and readily absorbed with a median tmax occurring at 4 h post dose, approximately 1 h later than that of Vumerity® capsules.
However, the mean MMF Cmax from Bafiertam® (1969 ng/mL) was higher than that from Vumerity® (1121 ng/mL). The
mean MMF AUC0-t and AUC0-inf from Bafiertam® (3503 and 3531 h*ng/mL) were also higher than those from Vumerity®
(3123 and 3227 h*ng/mL), respectively. The geometric least-squares mean (GLSM) ratios
(90% confidence interval), Bafiertam® vs. Vumerity®, for MMF Cmax, AUC0-t and AUC0-inf were 181.8 (158.2 - 208.8)%, 116.8 (107.9–126.5)% and 113.8 (105.3 - 123.0)%, respectively.
Both products were safe and well tolerated, as expected, with flushing being the most
common adverse event for both products.
Conclusions
The mean MMF AUC0-t and AUC0-inf were 14–17% higher after administration of Bafiertam® as compared to Vumerity® at
their respective therapeutic doses under fasting conditions, however, this difference
was not statistically or clinically significant. Although more clinical studies would
be needed before making strong recommendations, results of this study may help with
selecting appropriate fumarate products, especially when administering the product
with food is clinically recommended.
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References
- Tecfidera® (Dimethyl Fumarate) Prescribing Information and Patient Information.Biogen, 2020 (Accessed 22 June 2020)
Biogen. Vumerity® (diroximel fumarate) prescribing information and patient information, 2021. DailyMed - VUMERITY- diroximel fumarate capsule (nih.gov). Accessed 16 December 2021.
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- Pharmacokinetics and bioavailability of monomethyl fumarate following a single oral dose of Bafiertam™ (monomethyl fumarate) or Tecfidera ® (dimethyl fumarate).CNS Drugs. 2021; 35 (MayEpub 2021 Mar 30): 567-574https://doi.org/10.1007/s40263-021-00799-9
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Article info
Publication history
Published online: January 03, 2023
Accepted:
January 2,
2023
Received in revised form:
December 25,
2022
Received:
July 18,
2022
Footnotes
☆This study has been registered with ClinicalTrials.gov (NCT05181215) on 6 January 2022.
Identification
Copyright
© 2023 Published by Elsevier B.V.
