DX39 Pregnancy Outcomes with Teriflunomide: Female Patients and Partners of Male Patients

Thursday, May 30, 2013
Lily Jung Henson, MD , Swedish Medical Center, Issaquah, WA
Olaf Stuve, MD , University of Texas Southwestern Medical Center at Dallas, Dallas, TX
Myriam Benamor, MD , Sanofi, Chilly Mazarin, France
Sandrine Turpault, PharmD , Sanofi, Bridgewater, NJ
Françoise Menguy-Vacheron, PhD , Sanofi, Chilly Mazarin, France

Background: Teriflunomide is a once-daily, oral disease-modifying therapy approved (USA/Australia) for relapsing forms of multiple sclerosis (MS). In animals, teriflunomide is teratogenic and embryolethal. However, in animals there was no evidence of an effect of teriflunomide on genes (three species) or fertility (rats). Furthermore, the offspring of treated male rats showed no external malformations. Teriflunomide is detected in semen in men on treatment.

Objectives: Summarize pregnancy outcomes in females and partners of males exposed to teriflunomide across nine phase 2/3 clinical studies in the MS clinical development program.

Methods: Despite the requirement that patients participating in teriflunomide clinical studies use effective contraception, a number of pregnancies were reported across the program in both female study patients and partners of treated male patients. Information on pregnancy outcomes was collected using a Drug Exposure Via Parent form (data cut-off: August 21, 2012).

Results: Seventy-one pregnancies were reported in female patients in the clinical program. Outcomes of the pregnancies were: induced abortion, n=34; spontaneous abortion, n=15; live births, n=17; ongoing pregnancy, n=5. Of the 71 pregnancies reported, 44 were in patients exposed to teriflunomide; the remaining pregnancies occurred in patients treated with placebo, interferon beta, or whom remained blinded with respect to treatment group. Of the 17 live births, 12 were to patients exposed to teriflunomide. Pregnancies were reported in 19 female partners of male patients; outcomes were: 2 induced abortions; 1 spontaneous abortion; 13 live births; and 3 ongoing pregnancies. All newborns reported across the program to date were healthy and without functional deficits or structural defects.

Conclusions: No teratogenicity has been reported in newborns of either females exposed to teriflunomide or partners of males exposed to teriflunomide in the clinical program to date. More prospective data are needed with respect to pregnancy outcomes. A pregnancy registry is planned.

Study supported by Genzyme, a Sanofi company.