New drugs for malaria! Novartis' novel combination therapy with MMV ganaplacide/lumefantrine-SDF will enter Phase 3 clinical development!

Nov.
25, 2022 /Biovalley BIOON/ -- Novartis and the non-profit organization Medicines for Malaria Venture (MMV) have jointly announced that the two parties have decided to advance ganaplacide/lumefantrine-solid dispersible (SDF) to Phase 3 clinical development as the threat of resistance to current antimalarial therapies increases.
It is used to treat patients
with acute uncomplicated malaria caused by Plasmodium falciparum.

Ganaplacide/lumefantrine-SDF is a novel combination therapy that is administered once
daily.
Among them, ganaplacide is a new type of drug with a completely new mechanism of action; Lumefantrine-SDF is an optimized formulation of lumefantrine that can be administered once a day instead of twice a day
.
The ganaplacide/lumefantrine-SDF combination has the potential not only to eliminate malaria infections, including those caused by artemisininin-resistant strains, but also to interrupt transmission of the malaria parasite
.
Currently, the combination therapy is being developed
with scientific and financial support from MMV and its partners.
In August 2022, the U.
S.
FDA granted fast-track designation (FTD) and orphan drug designation (ODD)
for the treatment of acute uncomplicated malaria with ganaplacide/lumefanfan-SDF combination therapies.

As previously announced, a phase 2 open-label randomized controlled study was conducted
in 524 adults and children with acute uncomplicated malaria due to Plasmodium falciparum infection.
The results showed that the ganaplacide/lumefantrine-SDF combination achieved its primary goal
in both adult and pediatric patients.
In patients who received ganaplacide/lumefantrine-SDF once daily for 3 days, the response rate was similar
to that observed in patients who received artemether-lumefantrine control therapy twice daily for 3 days.
Artemether-lumefantrine is currently the "gold standard" therapy
for acute uncomplicated malaria.

Novartis and MMV plan to initiate a large-scale head-to-head Phase 3 pivotal clinical trial in 2023 comparing ganaplacide/lumefantrine-SDF with the current "gold standard" artemether-lumefantrine
.
The trial will be conducted in collaboration with the WANECAM 2 consortium and will include collaborative clinical trial sites in Burkina Faso, Mali, Gabon, Niger and other sites in sub-Saharan Africa
.
Both Phase 2 and Phase 3 studies were funded
by the European and Developing Countries Clinical Trials Partnership (EDCTP), supported by the European Union.

Dr Sujata Vaidyanathan, Head of Global Health Development at Novartis, said: "The emergence of artemisinin resistance calls for urgent action to develop new antimalarial drugs
.
For drug-resistant malaria parasites, we need non-artemisinin-based drugs with novel mechanisms of action, as well as simple, easy-to-follow dosing schedules to help improve treatment adherence
.
The sooner we discover new compounds and the faster the world adopts them, the better our chances of defeating malaria parasite resistance
.
”

Dr Timothy Wells, Chief Scientific Officer of MMV, said: "We are increasingly seeing reduced sensitivity of malaria parasites to artemisinin, even in Africa
.
If successful, this new combination will increase the options available to countries around the world and help save the lives of
children at risk of this devastating disease.
”

Ganaplacide chemical structure (Image source: medchemexpress.
com)

According to the latest World malaria report, released in December 2021, there were an estimated 241 million malaria cases worldwide in 2020, resulting in 627,000 deaths
.
This represents an increase of more than 14 million malaria cases and more than 69,000 deaths in 2020 compared to 2019
.
About two-thirds (47,000) of the new deaths are related to
the disruption of malaria prevention, diagnosis and treatment interventions caused by COVID-19.

Plasmodium falciparum malaria is mainly treated with artemisinin-based combination therapies (ACTs) such as artemether-lumefantrine
.
ACTs are still very effective and well tolerated
.
Novartis launched the first fixed-dose combination ACT in 1993 and has since delivered more than 1 billion courses of antimalarial treatment
largely unprofitably.
Together with MMV, Novartis has developed a compound artemether flavor-masking dispersible formulation for children, which is currently used to treat more than 450 million children, mainly in Africa
.
However, the observed increased frequency of parasites that respond more slowly to artemisinin in some parts of East Africa (Rwanda, Uganda and the Horn of Africa) suggests the urgent need to develop a new non-artemisinin-based antimalarial drug to avoid a return to the high levels of the 90s in child
mortality.

Ganaplacide is the result of a joint research project supported by the Wellcome Trust, MMV, the Singapore Economic Development Board (SEDB) and the Novartis Institute for Tropical Diseases, the Novartis Research Foundation Genomics Institute and the Swiss Institute of
Tropical and Public Health.
The research project aims to discover the next generation of antimalarial drugs
.

In 2022, Novartis reaffirmed its commitment to malaria research and development at the Kigali Summit on Malaria and Neglected Tropical Diseases, announcing an investment of US$250 million to advance drug development
for malaria and neglected tropical diseases over a five-year period.
This includes next-generation antimalarial drugs, as well as a new artemisinin-lumefantrine formulation
for treating malaria infants under 5 years of age.
(Biovalley Bioon.
com)

Novartis and Medicines for Malaria Venture announce decision to move to Phase 3 study for novel ganaplacide/lumefantrine-SDF combination in adults and children with malaria