Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria Susan A. Charmana, Sarah Arbe-Barnesb, Ian C. Bathurstc, Reto Brund,e, Michael Campbella, William N. Charmana, Francis C. K. Chiua, Jacques Cholletd,e, J. Carl Craftc, Darren J. Creeka, Yuxiang Dongf, Hugues Matileg, Melanie Maurerd,e, Julia Morizzia, Tien Nguyena, Petros Papastogiannidisd,e, Christian Scheurerd,e, David M. Shackleforda, Kamaraj Sriraghavanf, Lukas Stingelina, Yuanqing Tangf, Heinrich Urwylerh, Xiaofang Wangf, Karen L. Whitea, Sergio Wittlind,e, Lin Zhouf, and Jonathan L. Vennerstromf,1 + Author Affiliations
aCentre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia; bFulcrum Pharma Developments Ltd., Hemel Hempstead, Hertfordshire HP1 1JY, United Kingdom; cMedicines for Malaria Venture, CH-1215 Geneva, Switzerland; dSwiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland; eUniversity of Basel, CH-4051 Basel, Switzerland; fCollege of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6025; gF. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland; and hBasilea Pharmaceutica Ltd., CH-4058 Basel, Switzerland Edited by Thomas E. Wellems, National Institutes of Health, Bethesda, MD, and approved January 11, 2011 (received for review October 21, 2010)
Abstract Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. OZ439 has successfully completed Phase I clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing Phase IIa trials in malaria patients. Herein, we describe the discovery of OZ439 and the exceptional antimalarial and pharmacokinetic properties that led to its selection as a clinical drug development candidate. In vitro, OZ439 is fast-acting against all asexual erythrocytic Plasmodium falciparum stages with IC50 values comparable to those for the clinically used artemisinin derivatives. Unlike all other synthetic peroxides and semisynthetic artemisinin derivatives, OZ439 completely cures Plasmodium berghei-infected mice with a single oral dose of 20 mg/kg and exhibits prophylactic activity superior to that of the benchmark chemoprophylactic agent, mefloquine. Compared with other peroxide-containing antimalarial agents, such as the artemisinin derivatives and the first-generation ozonide OZ277, OZ439 exhibits a substantial increase in the pharmacokinetic half-life and blood concentration versus time profile in three preclinical species. The outstanding efficacy and prolonged blood concentrations of OZ439 are the result of a design strategy that stabilizes the intrinsically unstable pharmacophoric peroxide bond, thereby reducing clearance yet maintaining the necessary Fe(II)-reactivity to elicit parasite death.
1,2,4-trioxolane antimalarial drug discovery
Posted by seibertneurolyme (Member # 6416) on :
May work for malaria but I have my doubts about babesia.
Says it is comparable to art derivatives and also mefloquine(larium). Unfortunately both of those often fail for babs.
Bea Seibert
Posted by Maradona (Member # 24552) on :
Yes but on research trials this drug is given just one time and cured the malaria on mice and small group of patients and is better tolereted (less side effects) in patients than drugs that are on the market for malaria today.
Posted by blinkie (Member # 14470) on :
I think we won't know until we try it or studies are done. Anything new is a good thing for those with babs.
I'm taking lariam and making good progress, added bactrim and made another huge leap in the right direction, added in puled artemisinin and making even greater strides.
This new med alone may not be enough but paired with other things could be the answer.
Posted by elizzza811 (Member # 24713) on :
Even if it would work, what are the chances that they'll allow babs positive people to take it when they won't even treat us for Lyme? Not upset with you...just the system.
Posted by Maradona (Member # 24552) on :
Always there is a way to get the drug thru different ways.
Just hopefully will cure the babesia and malaria alone or in combination with other meds and give the same results in a big populations of patients as in first and second fase.
A good thing that the new med past the second fase chances sre that it can hit the market in 2 years (around two years ).
Posted by nefferdun (Member # 20157) on :
I hope it works and it is approved.
Posted by Katrina (Member # 15236) on :
The very fact that they are working on new and different drugs for the treatment of Malaria is a very positive thing for those of us treating babesia.
It is very likely it may have some therapeutic effect on Babesia.
I have taken Malarone, Mepron, Coartem and Artemesia as well as Bactrim and they all have helped dramatically change my life. However, it is a long haul. Hopefully, this will add one more thing to the arsenal.
Thanks so much for the post. It is encouraging!
Katrina
Posted by daniel (Member # 22201) on :
i dont think that larium fails often! its a very strong drug, everybody here has different strains, maybe also strains which we even dont know. you just have to try which med is hitting the "secret bugs".
Posted by richedie (Member # 14689) on :
But could be many. many years till available.
Posted by migs (Member # 16496) on :
I don't know about Australia but American drug companies get drugs approved very quickly now.
This sounds very positive. Hopefully it turns out to be safe.