Preventerm inhibits three molecules that block contractions. The medication acts to prevent premature labor whatever the cause, be it infection, inflammation, bleeding, an overextended uterus, or too much amniotic fluid. Every day that a premature baby manages to stay in the womb increases their chances of survival, and a normal healthy life once they are born.
Premature birth is the leading cause of infant death in developed countries. It also accounts for half of all neurological handicaps in newborns, such as cerebral palsy, blindness, and developmental defects. Babies born at 22 weeks have a 10-15% survival rate. Those born just five weeks later have a 90% survival rate.
While more than one tenth of all births in the U.S. are delivered prematurely, until now there has been no failsafe measure to prevent it from happening
Now Israeli start-up Bioterm is developing a product called Preventerm that will help prolong pregnancy to full-term, help ensure that babies stay in the womb for those essential extra weeks, and in turn profoundly reduce neonatal mortality and morbidity rates.
The treatments practiced today attempt to prevent preterm birth are unsatisfactory. They include intravenous fluids and bed rest, tocolytic agents, such as uterine contraction inhibiting agents and surgical procedures that attempt to strengthen the cervix. In the worst-case scenarios, mothers taking a preterm labor drug may suffer a respiratory arrest and die. In the best-case scenarios, the delivery can be postponed for a few extra days.
Preventerm inhibits three molecules – including prostaglandins which are involved in pre-term birth – that block contractions. The medication acts to prevent premature labor whatever the cause, be it infection, inflammation, bleeding, an overextended uterus, or too much amniotic fluid.
Preventerm is based on a collagen inhibitor central to cervical flexibility. It can be administered vaginally from the second trimester up until birth, and it inhibits the final common pathways for triggering preterm birth, therefore effective regardless of the cause for labor.
Dr. Israel Shamir Leibovitz, founder and interim CEO of Bioterm, believes that Preventerm is far more effective than the existing treatments, with a 90% level of potency. He also says it has only minor side effects. Aside from the obvious advantages for the baby, Leibovitz points out that the product can also drastically reduce medical expenses. In the Western world, the cost of caring for premature babies is about $45 billion a year.
The idea of creating a preterm labor inhibitor started while Bioterm doctors were researching a drug candidate for labor induction.
“Once we found that collagenase is critically involved in parturition (giving birth) during labor, we decided that inhibiting collagenase and cytokines can be a great alternative for treating and preventing pre-term labor,” said Leibovitz, co-founder and CMO.
So far Bioterm has carried out a series of tests on mice, which showed that the product was successful at delaying pre-term labor. The company does not have to carry out phase I clinical trials on humans, which are designed to prove a product safe for human use, because the inhibitor molecule is already being used to treat pregnant women who suffer paracetamol poisoning. In this case the molecule is used intravenously.
To prevent pre-term births the molecule is used as a vaginal pessary that delivers a huge dose of the product to the cervix and uterus.
Bioterm is now about to carry out phase II trials. The first will be carried out at Tel Hashomer hospital in Tel Aviv and Ha’emek Hospital in Afula. One hundred pregnant women will take part: 50 of whom will be given a placebo. This trial should begin in one or two months. If all goes well and Bioterm receives approval from the Ministry of Health, the second part of the Phase II trial will be carried out at Case Western Hospital in Cleveland, Ohio, probably toward the end of the year.
Leibowitz estimates that Preventerm is expected to get FDA approval by 2006 and each treatment is expected to cost about $300. He further expects that the market potential for the Bioterm natural inhibitor is between $2.8 and $3.5b. a year.
Bioterm is also involved in developing another product to induce labor. Labor induction is an equally distressing condition for woman and child. Nearly one quarter of the births in the Western world are induced. It is a recommended procedure when the mother is 2 weeks past due, when she is diabetic, or when the baby is showing problems, such as growth retardation.
Given by local injections or cervical suppositories, Bioterm`s Inducterm can safely degrade membranes and cervical tissues to accelerate labor within a few hours, compared to a few days by other drugs. No side effects have been found and it may be used for other gynecological procedures.
Like Preventerm, Inducterm is based on the natural human collagenase product involved in the labor process. It starts labor by degrading the membranes in the uterus and since the molecule is large it will not cross the placenta barrier, significantly decreasing the side effects currently found through the use of prostaglandins. Inducterm is expected to decrease the number of C-sections, hospital stays and thus expenses, and improve patient comfort and delivery costs.
Phase III trials on Inducterm are expected to be finished by 2006. Bioterm is expected to accelerate through regulatory approvals its collagenase molecules that have been approved for unrelated indications, such as dermal wound healing.
Leibovitz, who works part-time as a gynecologist at Tel Hashomer hospital in Tel Aviv, began the research behind Bioterm some years ago. He founded Bioterm in 1996 with Prof. Eliezer Shalev, chairman of the Department of Obstetrics and Gynecology of Haemek Hospital, and Prof. Daniel Seidman, a senior physician and associate clinical professor at the Sackler School of Medicine at Tel-Aviv University. The company is based in Tel Aviv.
Though raising money is difficult these days and biotech is as badly affected as most other hi-tech industries, Leibovitz is optimistic.
“These are very appealing drugs,” he says. “In the US alone, $5b. is spent on neo-natal incubators every year. It can cost the state as much as $2m. just to help one child, and there’s no guarantee the child will be okay afterwards. With Preventerm we believe we can keep a baby in the best incubator there is for an extra few weeks.
“Everyone will be happy with that outcome.”
(Courtesy of Bio-Israel)