OBE022 is ObsEva's potential first-in-class, oral and selective PGF2alpha receptor antagonist
ObsEva SA (Nasdaq: OBSV), a Swiss biopharmaceutical company focused on the development and commercialization of novel therapeutics for serious conditions that compromise a woman's reproductive health and pregnancy, today announced that OBE022 was observed to exert a synergistic effect in combination with nifedipine on the delay of delivery in an animal model for preterm labor. OBE022 is a potential first-in-class, once daily, oral and selective prostaglandin F2alpha (PGF2alpha) receptor antagonist, which is in development for the treatment of preterm labor in weeks 24 to 34 of pregnancy. Nifedipine is a calcium channel blocker approved for the treatment of hypertension and used as standard of care in preterm labor. The results of this pharmacology study will be presented on March 18, 2017 at the Society for Reproductive Investigation's 64th Annual Scientific Meeting (Orlando, USA) (1).
The study evaluated the effect of OBE022 and nifedipine, alone and in combination with each other, on an animal model of RU486-induced parturition in pregnant mouse. The induction of labor by the antiprogestin RU486 results from inhibition of progesterone activation leading to the up-regulation of labor-associated proteins as seen in the case of idiopathic preterm labor.
Compared to the vehicle control, nifedipine (5mg/kg, taken orally), as well as OBE022 (100mg/kg, taken orally), alone demonstrated statistically significant delays in RU486-induced preterm labor. Combination treatment with OBE022 and nifedipine demonstrated a clear synergistic effect on the delay of delivery when compared to vehicle, nifedipine or OBE022 alone (p<0.001, p<0.001 and p<0.01, respectively).
The results of this study constitute an important step towards the development of our potential first-in-class PGF2alpha receptor antagonist, OBE022, in the treatment of preterm labor, as adding it to the standard of care will facilitate the clinical testing of OBE022 for the prevention of preterm birth, and more importantly may provide a winning therapeutic combination for that indication
Management of preterm labor remains an unmet medical need. Pan-prostaglandin inhibition with non-steroidal anti-inflammatory drugs (NSAID) is an effective treatment for preterm labor, but is limited due to severe and sometimes life-threatening adverse effects on the fetus. PGF2alpha is a naturally occurring prostaglandin that acts to induce labor in pregnant women. Through specific antagonism of the PGF2alpha receptor, OBE022 is designed to reduce PGF2alpha-mediated inflammation, decrease uterine contractions and prevent membrane ruptures and cervical changes, which are the key features of preterm labor resulting in preterm birth.
Currently, though not approved for this indication, one of the commonly used preterm labor treatments is the oral calcium channel blocker nifedipine. Therefore, selectively targeting the PGF2alpha receptor in combination with nifedipine may be an optimal strategy for preventing or delaying preterm delivery.
(1) Oliver Pohl, Murielle Méen, Philippe Lluel, André Chollet and Jean-Pierre Gotteland, Effect of OBE022, an oral and selective non-prostanoid PGF2alpha receptor antagonist in combination with nifedipine for preterm labor: a study on RU486-induced parturition of pregnant mice, Abstract # 32
