[Ip-health] Press release: ISMB assessment enables recruitment of 2-5 year olds into Phase IIb trial for next-generation single-dose cure for malaria

Elizabeth Poll polle at mmv.org
Tue Jan 20 07:38:21 PST 2015

Dear colleagues,

We have some exciting news to share with you: an Independent Safety Monitoring Board (ISMB) has recommended that recruitment of patients aged 2-5 years can begin for the ongoing Phase IIb safety and efficacy trial of a single dose of the antimalarial combination therapy OZ439/piperaquine phosphate.

This combination has the potential to be the long sought single dose cure for malaria. MMV and partners are therefore delighted that the medicine can now be offered, within the study setting, to patients from among the population that suffer the most from this deadly disease.

Please find the press release and notes for editors copied below and attached.

If you have any questions, don't hesitate to ask.

Best wishes,


Independent Safety Monitoring Board assessment enables recruitment of 2-5 year olds into Phase IIb trial for next-generation single-dose cure for malaria

* OZ439 (artefenomel) in combination with the established antimalarial piperaquine phosphate (PQP), is currently in a Phase IIb trial as the first potential single-dose cure for malaria.
* An assessment of safety data has led an Independent Safety Monitoring Board to conclude that OZ439/PQP is well-tolerated in adult patients as well as patients from 5 to 15 years. As a result, patients aged 2-5 years (among the primary target population for this medicine) may now also receive this treatment as part of the trial.
* MMV was able to achieve this milestone in collaboration with 10 trial sites from Burkina Faso, Gabon, Uganda and Vietnam. In addition, the following countries are also preparing to begin involvement, pending regulatory approval: Benin, Colombia, Democratic Republic of Congo and Mozambique.

Geneva, Switzerland, 20 January 2015. An Independent Safety Monitoring Board (ISMB) has recommended that recruitment of patients aged 2-5 years can begin for the ongoing Phase IIb safety and efficacy trial of a single dose of the antimalarial combination therapy OZ439 (artefenomel, a novel aromatic trioxolane)/piperaquine phosphate (PQP). The ISMB based this decision on assessment of safety data from over 80 patients, deeming it well-tolerated in patients above 5 years.

The main goal of the trial is to identify the optimal dose of OZ439/PQP. The ISMB's decision will now enable the correct dosage to be validated in the paediatric population, an important step given that the overwhelming burden of malaria is borne by children under 5 years of age.

If the programme is successful and the combination approved, it would add to the arsenal of malaria medicines. A single-dose treatment would help to improve patient compliance compared to current 3-day therapies.

The Phase IIb trial of OZ439/PQP began in July 2014 and will continue over the course of 2015 in eight countries: Benin, Burkina Faso, Colombia, DRC, Gabon, Mozambique, Uganda and Vietnam. Designed to deliver safety and efficacy data in young children as quickly as possible, the trial adopted a staggered approach, treating adults first, then, as sufficient safety data was obtained, extending to 5-15 year olds.

As of today (January 20th), 95 of the 495 patients required for the trial have been treated with the combination. Following the ISMB's recommendation, the treatment can now also be offered to 2-5 year olds (among the primary target population for this medicine). If the ISMB then deems it to be well-tolerated in this younger and more vulnerable group, the treatment can then be offered to infants aged 6 months to 2 years, the final age group in this trial, (also among the primary target population for this medicine).

"The safety data for this innovative combination antimalarial has been assessed in more than 60 adults and 20 children aged over 5 years," said Prof Dr Michael Ramharter, Coordinating Principal Investigator of the trial from the Medical University of Vienna and Albert Schweitzer Hospital, Lambaréné, Gabon where the first patient in this trial was enrolled. "The ISMB's recommendation after review of this data means that we can now enrol and treat children of 5 years and under in the efficacy study. This is a significant milestone, as we move closer to developing a potential single-dose cure that can not only be used by adults but also by young children, the population hardest hit by malaria."

"A single-dose cure would improve patient compliance considerably and would be a huge step forward for malaria treatment and its ultimate eradication," said Professor Dr Peter Kremsner, Director of the Institute for Tropical Medicine at the University of Tübingen, Germany and Scientific Director of the Albert Schweitzer Hospital in Gabon. "That's why testing a combination of the promising new compound, OZ439, with a known partner drug in a single-dose cure is so important. Medicines for Malaria Venture is dedicated to the eradication of this terrible disease and it's a privilege to work with them on this study."

"This trial is a key milestone in the development of OZ439," said Dr David Reddy, MMV's CEO. "Children below the age of 5 are the most vulnerable to malaria and the ISMB's confirmation that OZ439 is sufficiently well-tolerated to be offered to this young population in a study setting is a vital step towards developing a new cure appropriate for young children. This medicine could be a game changer for malaria case-management, as it also has the potential to be the long sought-after single-dose cure. The fact that almost 100 patients required in the trial have been dosed with this new combination is real credit to our partners. I applaud each of the 10 trial sites - it is their commitment and collaboration that has enabled us to achieve this milestone."

Notes for editors

About OZ439 (artefenomel)
The aromatic trioxolane, OZ439 is the first drug that MMV, together with its academic partners,[1] has independently brought forward from laboratory to clinic. OZ439 is a fully synthetic alternative to artemisinin derivatives. Phase IIa trials demonstrated that OZ439 has excellent activity against both P. falciparum and P. vivax, which together cause the majority of malaria cases worldwide. Because OZ439 has a longer half-life than artemisinin-derived compounds it stays in the blood for longer providing an ideal foundation for a single-dose malaria cure, and is being investigated in combination with both novel and existing antimalarials, such as piperaquine.

About a single dose cure for malaria
A single-dose cure would be a major treatment advance compared to currently available 3-day therapies, as it would enable healthcare workers to guarantee patients receive a complete curative dose of treatment. This is important, as we know that patients often do not complete the full course of treatment once they see their symptoms improve and unfortunately, this proves a perfect breeding ground for drug resistance.

About Medicines for Malaria Venture (MMV)
MMV is recognized as the leading product development partnership (PDP) in the field of antimalarial drug research and development. Its mission is to reduce the burden of malaria in disease-endemic countries by discovering, developing and facilitating delivery of new, effective and affordable antimalarial drugs.

Since its foundation in 1999, MMV has developed and brought to registration four new medicines with its partners: Pyramax®, (pyronaridine-artesunate) co-developed with Shin Poong; Eurartesim® (dihydroartemisinin-piperaquine) with Sigma-Tau; Guilin's artesunate injection for the treatment of severe malaria, Artesun®; and Coartem® Dispersible (artemether-lumefantrine), a child-friendly formulation developed with Novartis. Since 2009, over 250 million courses of Coartem Dispersible treatment have been supplied to 50 malaria-endemic countries; and since prequalification in 2010, an estimated 25 million vials of artesunate injection have been delivered, saving an additional 165,000 young lives.

Managing the largest portfolio of antimalarial R&D projects ever assembled, of over 65 projects, MMV has seven new drugs in clinical development addressing unmet medical needs in malaria, including medicines for children, pregnant women and relapsing malaria, and drugs that could support the elimination/eradication agenda. MMV's success in research and access & product management comes from its extensive partnership network of over 300 pharmaceutical, academic and endemic-country partners in 50 countries.

MMV's vision is a world in which innovative medicines will cure and protect the vulnerable and under-served populations at risk of malaria, and ultimately help to eradicate this terrible disease.
For more information, please visit http://www.mmv.org

For more information:

Dr. Ghyslain Mombo-Ngoma
Albert Schweitzer Hospital, Medical Research Unit, Epidemiology & Control of Infectious Disease
Lambaréné,[2] Gabon and
Eberhard-Karls-University of Tübingen, Department of Tropical Medicine
Tel.: +24 1 0709 2785
Email: ghyslain.mombongoma at gmail.com

Assoc. Prof. Dr. Michael Ramharter
Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine
Medical University of Vienna1 and
CERMEL (Centre de Recherches Médicales de Lambaréné)
Albert Schweitzer Hospital2
Lambaréné, GABON
Tel.: +43 1 40400 44400
Email: michael.ramharter at meduniwien.ac.at

[1]The collaborative research activities between the CERMEL (Centre de Recherches Médicales de Lambaréné), MMV, and the Medical University of Vienna are co-funded by the Austrian Ministry of Science, Research, and Economy.
2 The Albert Schweitzer Hospital, Gabon, is part of the German Center for Infection Research (DZIF) and receives funding for a clinical research group from the Federal Ministry of Education and Research (BMBF), Germany, via DZIF.

Prof. Dr. Peter G. Kremsner
Centre de Recherches Medicales de Lambaréné, Gabon and Universitätsklinikum Tübingen, Instititut für Tropenmedizin Germany
Tel.: +49 7071 2987179
Email: peter.kremsner at uni-tuebingen.de

Jaya Banerji
Director Communications and Advocacy, MMV
Tel: +41 22 555 0327
Mob: +41 79 707 7181
Email: banerjij at mmv.org

MMV Disclaimer
This document contains certain forward-looking statements that may be identified by words such as 'believes', 'expects', 'anticipates', 'projects', 'intends', 'should', 'seeks', 'estimates', 'future' or similar expressions, or by discussion of, among other things, vision, strategy, goals, plans, or intentions. It contains hypothetical future product target profiles, development timelines and approval/launch dates, positioning statements, claims and actions for which the relevant data may still have to be established. Stated or implied strategies and action items may be implemented only upon receipt of approvals including, but not limited to, local institutional review board approvals, local regulatory approvals, and following local laws and regulations. Thus, actual results, performances or events may differ from those expressed or implied by such statements.

We ask you not rely unduly on these statements. Such forward-looking statements reflect the current views of Medicines for Malaria Venture (MMV) and its partner(s) regarding future events, and involve known and unknown risks and uncertainties.

MMV accepts no liability for the information presented here, nor for the consequences of any actions taken on the basis of this information. Furthermore, MMV accepts no liability for the decisions made by its pharmaceutical partner(s), the impact of any of their decisions, their earnings and their financial status.

Elizabeth Poll | Medicines for Malaria Venture
Editor and Publications Officer
T: +41 22 555 03 17 | M: +41 79 907 59 92
Email: polle at mmv.org

Defeating Malaria Together | www.mmv.org


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