Diseases and Products | Preterm Labor
Quick Links:
Disease Overview:
Preterm labor is defined as the onset of uterine contractions before term and is the leading cause of neonatal mortality and a substantial portion of all birth-related short- and long-term morbidity. Successfully inhibiting preterm labor is known to reduce the risk of neonatal complications.
Market Overview:
According to a November 2002 publication in Obstetrics& Gynecology, preterm labor is the leading cause of neonatal mortality and a substantial portion of all birth-related short and long-term morbidity. Successful inhibition of premature birth is known to reduce the risk of complications. Despite extensive research into preterm labor during the past several decades, the rate of premature births has not decreased. According to the National Vital Statistics Reports issued by the U.S. Department of Health and Human Services, there were more than 4,000,000 births in the United States in 2005, almost 13% of which were considered preterm births. The U.S. Department of Health and Human Services estimates that the cost of intensive care unit, or ICU, services for premature infants is over $15.0 billion annually. In addition, according to a September 2004 publication in British Medical Journal, approximately 6% to 7% of all births in Europe occur before term.
Currently, therapy for preterm labor remains targeted at uterine contractions. ß2-adrenergic receptor agonists are generally used as first-line treatments for premature labor. The only FDA-approved treatment for preterm labor is ritodrine, a ß2 agonist. However, ritodrine has not been available for sale in the U.S. market since 1999. The more widely used treatment for preterm labor is another ß2 agonist, terbutaline; however, this drug is not approved by the FDA for preterm labor. Atosiban, an oxytocin antagonist, is available in Europe, but was denied regulatory approval in the United States. The usefulness of these ß2-adrenergic receptor agonists is often limited by the adverse reactions they produce, which include cardiovascular side effects such as heart palpitations. As a result, we believe that there is a need for treatments with better safety and tolerability profiles that are effective in reducing the premature birth rate and/or providing for longer gestation.
MN-221 for the Treatment of Preterm Labor:
MN-221 is a novel, highly selective β2-adrenergic receptor agonist under development for the treatment of preterm labor. In pre-clinical pharmacology studies in pregnant rats and sheep conducted by Kissei Pharmaceutical, MN-221 reduced the number of spontaneous or drug-induced uterine contractions in those animal models. In rat and sheep studies in which MN-221 was compared to ritodrine and/or terbutaline, the potency of MN-221 was greater than those β2-adrenergic receptor agonists. Furthermore, in these studies, MN-221 delayed both normal and preterm labor in rats and caused a marked increase in the bodyweight of rat pups as a result of prevention of premature birth. Moreover, the β1-adrenergic receptor stimulating activity of MN-221 was less than that of other β2-adrenergic receptor agonists in isolated rat atrium and in cardiac function tests in rats, dogs and sheep. These results suggest that MN-221 may be effective in reducing premature births and/or providing for longer gestation, while avoiding the stimulating action on the heart of older, less selective β2-adrenergic receptor agonists, due to its greater β2-adrenergic receptor selectivity.
MN-221 pharmacokinetic and safety data has been generated in Phase I clinical studies in healthy male and non-pregnant female volunteers conducted by Kissei Pharmaceutical in Japan and the U.K. MN-221 was generally well tolerated, and the adverse events were mild and typical of beta 2 adrenergic receptor agonist. A pilot double-blind, placebo-controlled Phase II clinical trial of MN-221 was completed in 2004 by Kissei Pharmaceutical in the U.K. A trend towards a reduction in the number of uterine contractions was observed in MN-221-treated patients.
A U.S. IND for MN-221 was filed by MediciNova in December 2004 and activated in January 2005. To date, pharmacokinetic and safety data has been generated from human experience with MN-221 through Phase I clinical studies in healthy male and non-pregnant female volunteers conducted by Kissei Pharmaceutical in Japan and the U.K. and a Phase I clinical trial in the United States conducted by us. A total of 244 healthy subjects received intravenous infusions of either MN-221 or a placebo. MN-221 was generally well tolerated. A pilot double-blind, placebo-controlled Phase II clinical trial of MN-221 was completed in 2004 by Kissei Pharmaceutical in seven women in preterm labor in the U.K. A trend towards a reduction in the number of uterine contractions was observed in MN-221-treated women and, as a result, only limited conclusions could be drawn from this clinical trial. No serious adverse events related to MN-221 were observed in this clinical trial.
We initiated a Phase Ib clinical trial in healthy pregnant women in the third quarter of 2006. Ten healthy, pregnant volunteers who were not in labor participated in this clinical trial, which was completed in the second quarter of 2007. The volunteers received a single-dose intravenous infusion regimen of MN-221, consisting of two consecutive rounds of a 15-minute priming and a 105-minute maintenance infusion to deliver 294 micrograms of MN-221 over four hours. The primary objectives of this clinical trial were to determine the pharmacokinetics, safety and tolerability of this infusion regimen of MN-221 in pregnant women. No significant safety concerns with MN-221 were identified in this clinical trial.
We will limit our development efforts on MN-221 for the treatment of preterm labor to those activities necessary to maximize MN-221’s value for such indication while pursuing a variety of initiatives to monetize this product candidate.
More Information
Click for more information on the following items:
Core Candidates:
Non-Core Candidates:
