Abstract: Pregnancy Data From The BG-12 (Dimethyl Fumarate) Development Program (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Thursday, May 30, 2013

Ralf Gold, MD , St Josef Hospital, Ruhr University, Bochum, Germany, Bochum, Germany

J. Theodore Phillips, MD PhD FAAN , Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, USA, Dallas, TX

Eva Havrdova, MD, PhD , Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, Prague, Czech Republic

Amit Bar-Or, MD, FRCPC , Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada, Montreal, QC, Canada

Ludwig Kappos, MD , University Hospital, Basel Neurology, Basel, Switzerland, Basel, Switzerland

Huixing Yuan, PhD , Biogen Idec Inc., Weston, MA, USA, Cambridge, MA

Mark Novas, MD , Biogen Idec Inc., Weston, MA, USA, Cambridge, MA

Marianne T. Sweetser, MD, PhD , Biogen Idec Inc., Weston, MA, USA, Cambridge, MA

Vissia Viglietta, MD , Biogen Idec Inc., Weston, MA, USA, Cambridge, MA

Robert J. Fox, MD, FAAN , Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH

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Background: Although pregnancies occurred during the BG-12 (dimethyl fumarate) clinical development program, no formal studies of BG-12 were conducted in pregnant women.

Objectives: To present data from animal reproductive toxicology studies and pregnancy outcomes reported during the BG-12 preclinical and clinical development program.

Methods: In preclinical studies, reproductive and developmental toxicology was evaluated in rats and rabbits given BG-12 during organogenesis or during pregnancy and lactation. In clinical trials, all subjects were required to use contraception and discontinue drug in the event of pregnancy. Outcomes of pregnancies occurring in BG-12 clinical studies (including 2,665 patients with MS, 320 psoriasis patients, 101 rheumatoid arthritis patients and 338 healthy volunteers) at the data cutoff are presented.

Results: No evidence of impaired fertility in rats or teratogenicity in rats and rabbits given BG-12 at doses that caused reductions in maternal weight gain were observed. As of 23 April 2012, 53 pregnancies were reported including 35 in subjects exposed to BG-12 (34 MS patients and 1 healthy volunteer), 14 in placebo recipients and 4 in patients exposed to another active treatment (glatiramer acetate). Pregnancy outcomes are known for 25 of 35 BG-12 recipients and include 15 live births (60%), 3 spontaneous abortions (12%) and 7 elective terminations (28%). Information on pregnancy outcomes is pending for 10 subjects. In 14 subjects given placebo, 9 live births (64%), 3 spontaneous abortions (21%) and 2 elective terminations (14%) were reported. There were no reports of fetal abnormalities. The incidence of spontaneous abortion in both BG-12 - and placebo-treated subjects was consistent with the expected rate of early pregnancy loss in the general population.

Conclusions: To date, pregnancy data indicate no increased risk of fetal abnormalities or adverse pregnancy outcomes associated with gestational exposure to BG-12 during the first trimester. Further data regarding pregnancies will be collected through a pregnancy registry.

SC15 Pregnancy Data From The BG-12 (Dimethyl Fumarate) Development Program