The DEEP study was designed to investigate whether treatment with a DIF (Digibind®*, GlaxoSmithKline) could influence the progression of the disease by neutralising endogenous digoxin-like factors (EDLFs) which are produced by the placenta and are present at higher levels in some women with pre-eclampsia. The study involved 51 women with severe pre-eclampsia who were in the 24th â 34th week of pregnancy, and for whom delivery of the baby was considered necessary within 72 hours to prevent possible life-threatening complications for the mother or baby. Women received either Digibind or placebo every 6 hours for up to 48 hours. The well-being of both the mother and baby were assessed for up to 24 hours after the birth and also at 6 weeks.
The main symptoms of pre-eclampsia in the mother are a rise in blood pressure and the appearance of protein in the urine, which indicates that the kidney may not be functioning properly. The two primary endpoints of the study were creatinine clearance, a measure of kidney function and the use of antihypertensive medication to lower blood pressure. The DEEP study met one of the primary endpoints in that the deterioration in kidney function during the 24-48 hours period of treatment was significantly less (p<0.05) in patients receiving Digibind compared to patients receiving placebo. However, in this study there was no significant difference for the other primary endpoint, the use of antihypertensive drugs. There was also no significant difference between Digibind and placebo in the time to delivery of the baby, although the study was not powered to show statistical significance for this secondary endpoint. None of the mothers receiving Digibind reported side effects to treatment with Digibind.
Protherics licensed the intellectual property rights to use DIFs in pre-eclampsia from Glenveigh Pharmaceuticals LLC in December 2006. Protherics paid a $5 million upfront payment to Glenveigh and assumed responsibility for completing the DEEP study. Under the terms of the contract, Protherics will now make an additional $5 million milestone payment to Glenveigh.
Andrew Heath, Chief Executive of Protherics, commented: "The DEEP study results provide evidence to support our hypothesis that, through the neutralisation of EDLFs, treatment with a DIF might be able to improve the outcome for women with this life threatening condition during pregnancy. However, the results from this small and complex study are not conclusive and further analysis of the full data will be required to determine the direction of the programme."
Pre-eclampsia is a life-threatening disorder occurring in 10% of pregnancies worldwide per year. It is characterised by high blood pressure and can lead to renal failure and seizures. It typically results in the early delivery of the baby, with potential developmental abnormalities and the possible death of the mother and/or baby.
By conservative estimates, pre-eclampsia and other hypertensive disorders of pregnancy are responsible for 76,000 deaths each year in the US. Pre-eclampsia is also a major cause of admission of babies into Neonatal Intensive Care Units (NICU). Currently there are no approved therapies available to treat pre-eclampsia and few products in development.
The cause of pre-eclampsia has not been conclusively identified but several vasoactive substances called endogenous digoxin-like factors (EDLFs) have been identified in the blood and placenta of women with pre-eclampsia. These EDLFs rapidly disappear following delivery of the baby, coincident with the disappearance of the symptoms of pre-eclampsia. Both Digibind and DigiFab™ (Protherics), which have been found to bind to EDLFs in vitro, may have potential application in the treatment of pre-eclampsia.
About Digoxin Immune Fabs
Digibind and DigiFab™ are intravenously administered polyclonal antibody fragments (Fab) designed to bind and neutralize digoxin. These products are used in the treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose.
Digoxin is the most commonly used cardiac glycoside in the treatment of congestive heart failure, and is also used to slow heart rate in some cardiac disturbances. Digoxin toxicity can cause potentially life-threatening heart rhythm disturbances, ranging from very slow to rapid ventricular rhythms.
*Digibind is a trademark of the GlaxoSmithKline group of companies
Protherics (LSE: PTI, NASDAQ: PTIL) is a leading biopharmaceutical company focused on the development, manufacture and marketing of specialised products for critical care and cancer.
Protherics has developed and manufactures two biologics for critical care which are FDA approved and currently sold in the US: CroFab™, a pit viper antivenom and DigiFab™, a digoxin antidote. The Company's strategy is to use the revenues generated from its marketed and out-licensed products to help fund the advancement of its broad, late stage pipeline.
Protherics has two major development opportunities in its critical care portfolio. CytoFab™ is being developed by AstraZeneca, for the treatment of severe sepsis, after a major Â£195 million licensing deal with AstraZeneca in December 2005. AstraZeneca is currently conducting an additional, expanded phase 2 programme. In addition, Protherics has today reported the results from a phase 2b study with Digoxin Immune Fab for the treatment of pre-eclampsia.
Protherics has a pipeline of four novel cancer products in clinical development, and intends to undertake the sales and marketing of these products in the US and or the EU. Protherics is preparing to resubmit a BLA for Voraxaze™, an adjunct to high dose methotrexate therapy, under a rolling submission in the US starting in H1 2008.
Protherics has a strong cash position, with cash balances at 30 September 2007 of Â£46.9 million, having completed a Â£38 million equity fundraising in January 2007 and received a Â£10 million milestone payment from AstraZeneca in April 2007.
With headquarters in London, the Company has approximately 290 employees across its operations in the UK, US and Australia.
For further information visit: www.protherics.com