ATP2A1 inhibitors(Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 inhibitors), SERCA2 inhibitors(Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Acute MalariaMalariaMalaria, Falciparum

Inactive Indication-

Originator Organization

Novartis Pharma AG

Active Organization

Novartis Pharmaceuticals Corp.

KPC Pharmaceuticals, Inc.Chodang Pharm Co., Ltd.

Inactive Organization

Novartis AG

Drug Highest PhaseApproved

First Approval Date

CN (01 Jan 1992),

Malaria

RegulationOrphan Drug (US)

Structure

Molecular FormulaC46H58Cl3NO6

InChIKeyZVAQGQOEHFIYMQ-UGOKYLLISA-N

CAS Registry141204-94-6

214

Clinical Trials associated with Artemether/Lumefantrine

NCT04704999 / Not yet recruitingPhase 4IIT

Optimizing the Dose of Tafenoquine for the Radical Cure of Plasmodium Vivax Malaria in Southeast Asia

Tafenoquine was recently approved by regulatory authorities in the USA and Australia. Tafenoquine is an alternative radical curative treatment to primaquine acting against the dormant liver stage of Plasmodium vivax (the hypnozoite). Tafenoquine (an 8-aminoquinoline) has the substantial advantage of single dosing as compared to a 14-day course of primaquine to achieve radical cure. The recommended tafenoquine dose is 300 mg, which was shown to be significantly worse in radical curative efficacy to a total primaquine dose of 3.5 mg/kg in Southeast Asia. The cure rate of tafenoquine 300 mg in Southeast Asian study sites was only 74%. The comparator 3.5 mg/kg total primaquine dose is the standard and most commonly used dose globally, but in Southeast Asia and the Western Pacific, higher doses of primaquine are needed for radical cure. This study aims to determine the optimal dose of tafenoquine in Southeast Asia.

Start Date01 Aug 2024

Sponsor / Collaborator

University of Oxford

NCT06424002 / Not yet recruitingPhase 4IIT

The Impact, Feasibility Acceptability and Cost Effectiveness of the RTS,S/AS01 Malaria Vaccine in School Aged Children

Across sub-Saharan Africa, school-age children bear an under-appreciated burden of malaria. An estimated 200 million school-age children are at risk of malaria and in many areas prevalence of infection exceeds 50%. The high infection rates in this group serves as a source of onward parasite transmission, undermining elimination and control efforts. Furthermore, malaria illness and malaria-induced anemia in this age group lead to school absenteeism, and impaired cognitive function and classroom attention, ultimately resulting in reduced academic achievement. Although universal malaria interventions, such as insecticide treated nets (ITNs) and access to prompt diagnosis and treatment are available to school-age children, this age group is the least likely to benefit from these interventions. Furthermore, efficacy of these approaches may be compromised by increasing anti-malarial drug and insecticide resistance. A malaria vaccine could help to avert the burden of malaria in this age group.
The RTS,S/AS01 malaria vaccine has recently been recommended for vaccination of young children (< 24 months) by the World health organization (WHO) after a Phase 3 trial and an implementation trial showed that the vaccine had moderate but significant efficacy to prevent clinical and severe malaria in young children. Previous randomized trials suggest that the vaccine is safe for older children. However, efficacy of the vaccine has never been assessed in school age children. Kamuzu University of Health Sciences in partnership with the Malawian Ministry of Health seeks to evaluate the efficacy of the newly introduced RTSS/AS01 malaria vaccine in school aged children. The study hypothesizes that vaccination will decrease the morbidity and transmission of malaria, as well as improve school absenteeism and educational outcomes.

Start Date01 Jun 2024

Sponsor / Collaborator

Kamuzu Central Hospital

[+3]

NCT06294912 / RecruitingPhase 1

A Controlled Human Malaria Infection Study to Evaluate the Antimalarial Activity of MK-7602 Against Plasmodium Falciparum Blood Stage Infection in Healthy Adult Participants

The purpose of this study is to assess the antimalarial activity, pharmacokinetics, and safety of MK-7602 in healthy adults following Plasmodium falciparum (P. falciparum) infection.

Start Date18 Apr 2024

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with Artemether/Lumefantrine

100 Translational Medicine associated with Artemether/Lumefantrine

100 Patents (Medical) associated with Artemether/Lumefantrine

743

Literatures (Medical) associated with Artemether/Lumefantrine

01 Apr 2024·Cytokine

Subchronic doses of artemether-lumefantrine, ciprofloxacin and diclofenac precipitated inflammatory and immunological dysfunctions in female Wistar rats

Article

Author: Sanmi Adekunle, Adeniran ; Temidayo Ige, Peace ; Bukoye Oyewo, Emmanuel ; Ayomide Akomolafe, Peter ; Oluwafunmilayo Ajayi, Juliana

Recents reports have shown increases in the abuse of anti-malaria, antibiotic and analgesic drugs. This study evaluated the effects of co-administration of artemether-lumefantrine (AL), ciprofloxacin (CPX) and diclofenac (DFC) on inflammatory and immunological status of female Wistar rats. Ninety-six female Wistar rats were assigned into eight groups of twelve animals each. Group A was control, groups B, C, D, E, F, G and H were administered AL, CPX, DFC, AL + CPX, AL + DFC, CPX + DFC and AL + CPX + DFC respectively. Dosages of administered drugs were 178 mg/kg b/w of AL, 185 mg/kg b/w of CPX and 9 mg/kg b/w of DFC. Animals were sacrificed after 6 and 12 weeks of oral administration. Blood was obtained through cardiac puncture. The liver was harvested and processed for immunohistochemical analysis. Differential leukocyte count and neutrophil adhesion test was conducted on whole blood. Immunological response was assessed by the serum levels of C-reactive protein (CRP), interleukin-1β (Il-1β), interleukin-6 (Il-6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), myeloperoxidase, and total immunoglobulin G. Data were analyzed with Graph pad prism 5, using one way analysis of variance at 5 % level of significance. Total leukocyte, lymphocyte and basophils count increased (p<0.05) in B, C, E, F, G and H, while neutrophil count decreased (p<0.05) in D, E, G and H at 6 weeks. Neutrophil adhesion decreased (p<0.05) in B, E, F, G and H at 6 weeks. There was no significant difference (p>0.05) in the expression of Il-6, MCP-1 and VCAM-1 across the groups. Il-1β decreased in H, while CRP increased in H at 6 weeks and 12 weeks. MPO activity decreased (p<0.05) in B, C, D, E, G and H at 6 weeks, but increased (p<0.05) in D and G at 12 weeks. Immunohistochemical analysis indicated increase (p<0.05) in tumour necrosis factor-α in liver tissues of B, C, D, E, F and G, while nuclear factor erythroid 2-related factor 2 increased (p<0.05) in C, D, E, F and G, but decreased (p<0.05) in H at 12 weeks. The co-administration of AL, CPX and DFC induced inflammatory responses with attendant immunological dysfunctions and liver damage.

28 Dec 2023·Journal of travel medicine

Emergence of artemisinin-based combination treatment failure in patients returning from sub-Saharan Africa with P. falciparum malaria

Article

Author: Paran, Yael ; Studentsky, Liora ; Dzikowski, Ron ; Manor, Uri ; Schwartz, Eli ; Vainer, Julia ; Grossman, Tamar

Abstract:

Background:

Artemisinin-based combination therapies (ACTs) are recommended as first-line treatment against uncomplicated Plasmodium falciparum infection. Mutations in the PfKelch13 (PF3D7_1343700) gene led to resistance to artemisinin in Southeast Asia. Mutations in the Pfcoronin (PF3D7_1251200) gene confer reduced artemisinin susceptibility in vitro to an African Plasmodium strain, but their role in clinical resistance has not been established.

Methods:

We conducted a retrospective observational study of Israeli travellers returning from sub-Saharan Africa with P. falciparum malaria, including patients with artemether–lumefantrine (AL) failure. Blood samples from all malaria-positive patients are delivered to the national Parasitology Reference Laboratory along with personal information. Confirmation of malaria, species identification and comparative parasite load analysis were performed using real-time PCR. DNA extractions from stored leftover samples were analysed for the presence of mutations in Pfkelch13 and Pfcoronin. Age, weight, initial parasitaemia level and Pfcoronin status were compared in patients who failed treatment vs responders.

Results:

During 2009–2020, 338 patients had P. falciparum malaria acquired in Africa. Of those, 15 (24–69 years old, 14 males) failed treatment with AL. Four were still parasitemic at the end of treatment, and 11 had malaria recrudescence. Treatment failure rates were 0% during 2009–2012, 9.1% during 2013–2016 and 17.4% during 2017–2020. In all patients, the Pfkelch13 propeller domain had a wild-type sequence. We did find the P76S mutation in the propeller domain of Pfcoronin in 4/15 (28.6%) of the treatment-failure cases compared to only 3/56 (5.5%) in the successfully treated patients (P = 0.027).

Conclusion:

AL treatment failure emergence was not associated with mutations in Pfkelch13. However, P76S mutation in the Pfcoronin gene was more frequently present in the treatment-failure group and merits further investigation. The increase of malaria incidence in sub-Saharan-Africa partly attributed to the COVID-19 pandemic might also reflect a wider spread of ACT resistance.

01 Dec 2023·Lancet (London, England)Q1 · MEDICINE

Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial

Q1 · MEDICINE

Article

Author: Thriemer, Kamala ; Panggalo, Lydia Vista ; Simpson, Julie A ; Kiros, Fitsum Getahun ; Lee, Grant ; Sutanto, Inge ; Mnjala, Hellen ; Ley, Benedikt ; Karahalios, Amalia ; Sadhewa, Arkasha ; Satyagraha, Ari Winasti ; Ekawati, Lenny L ; Hossain, Mohammad Sharif ; Degaga, Tamiru Shibiru ; Kibria, Mohammad Golam ; Price, Ric N ; Tego, Tedla Teferi ; Baird, J Kevin ; Weston, Sophie ; Rajasekhar, Megha ; Hailu, Asrat ; Anose, Rodas Temesgen ; Woyessa, Adugna ; Christian, Michael ; Rumaseb, Angela ; Alam, Mohammad Shafiul ; Abate, Dagamawie Tadesse

BACKGROUND:

In areas co-endemic for Plasmodium vivax and Plasmodium falciparum there is an increased risk of P vivax parasitaemia following P falciparum malaria. Radical cure is currently only recommended for patients presenting with P vivax malaria. Expanding the indication for radical cure to patients presenting with P falciparum malaria could reduce their risk of subsequent P vivax parasitaemia.

METHODS:

We did a multicentre, open-label, superiority randomised controlled trial in five health clinics in Bangladesh, Indonesia, and Ethiopia. In Bangladesh and Indonesia, patients were excluded if they were younger than 1 year, whereas in Ethiopia patients were excluded if they were younger than 18 years. Patients with uncomplicated P falciparum monoinfection who had fever or a history of fever in the 48 h preceding clinic visit were eligible for enrolment and were required to have a glucose-6-dehydrogenase (G6PD) activity of 70% or greater. Patients received blood schizontocidal treatment (artemether-lumefantrine in Ethiopia and Bangladesh and dihydroartemisinin-piperaquine in Indonesia) and were randomly assigned (1:1) to receive either high-dose short-course oral primaquine (intervention arm; total dose 7 mg/kg over 7 days) or standard care (standard care arm; single dose oral primaquine of 0·25 mg/kg). Random assignment was done by an independent statistician in blocks of eight by use of sealed envelopes. All randomly assigned and eligible patients were included in the primary and safety analyses. The per-protocol analysis excluded those who did not complete treatment or had substantial protocol violations. The primary endpoint was the incidence risk of P vivax parasitaemia on day 63. This trial is registered at ClinicalTrials.gov, NCT03916003.

FINDINGS:

Between Aug 18, 2019, and March 14, 2022, a total of 500 patients were enrolled and randomly assigned, and 495 eligible patients were included in the intention-to-treat analysis (246 intervention and 249 control). The incidence risk of P vivax parasitaemia at day 63 was 11·0% (95% CI 7·5-15·9) in the standard care arm compared with 2·5% (1·0-5·9) in the intervention arm (hazard ratio 0·20, 95% CI 0·08-0·51; p=0·0009). The effect size differed with blood schizontocidal treatment and site. Routine symptom reporting on day 2 and day 7 were similar between groups. In the first 42 days, there were a total of four primaquine-related adverse events reported in the standard care arm and 26 in the intervention arm; 132 (92%) of all 143 adverse events were mild. There were two serious adverse events in the intervention arm, which were considered unrelated to the study drug. None of the patients developed severe anaemia (defined as haemoglobin <5 g/dL).

INTERPRETATION:

In patients with a G6PD activity of 70% or greater, high-dose short-course primaquine was safe and relatively well tolerated and reduced the risk of subsequent P vivax parasitaemia within 63 days by five fold. Universal radical cure therefore potentially offers substantial clinical, public health, and operational benefits, but these benefits will vary with endemic setting.

FUNDING:

Australian Academy of Science Regional Collaborations Program, Bill & Melinda Gates Foundation, and National Health and Medical Research Council.

News (Medical) associated with Artemether/Lumefantrine

24 Apr 2024

·www.globenewswire.com

Novartis and Medicines for Malaria Venture announce positive efficacy and safety data for a novel treatment for babies <5 kg with malaria

There is currently no evidence-based treatment for the smallest babies with malaria The CALINA study tested a new ratio and dose of Coartem® (artemether- lumefantrine) to account for metabolic differences in babies under 5 kg The CALINA trial indicated that the new formulation has good efficacy and safety, and the data have been submitted for regulatory review Basel, April 24, 2024 – Novartis and Medicines for Malaria Venture (MMV) announce positive data from their phase II/III CALINA study, demonstrating that a novel formulation of Coartem® (artemether-lumefantrine) developed for babies weighing less than 5kg with malaria has the required pharmacokinetic profile and good efficacy and safety. The trial was conducted in several African countries. The data, which will be presented this week at the Multilateral Initiative on Malaria (MIM Society) 8th Pan-African Malaria Conference in Kigali, have been submitted for regulatory review. Malaria exerts a massive burden on public health across the world, particularly in Africa1. Huge strides have been made in recent decades in the treatment of malaria. However, to date, little data has been generated in the smallest children – babies less than 5 kg. “We are pleased with the positive outcomes from our CALINA study and to be one step closer to bringing an effective malaria treatment to all age groups, including vulnerable newborn babies," said Shreeram Aradhye, President, Development and Chief Medical Officer at Novartis. “We have been committed to the fight against malaria for more than two decades, and this successful trial represents another milestone towards ensuring that all people have access to an appropriate antimalarial therapy.” The CALINA study is led by Novartis, with the scientific and financial support of Medicines for Malaria Venture (MMV), and as part of the PAMAfrica consortium, which is funded by the European & Developing Countries Clinical Trials Partnership (EDCTP2). It is the first evidence-based trial conducted to evaluate a new antimalarial dose and regimen for all infants weighing under 5 kg with acute uncomplicated malaria. If approved, Novartis and MMV aim to make the treatment available as soon as possible to the youngest infants, who currently lack access to evidence-based treatment options. The new formulation, known as Coartem <5 kg Baby, uses a new ratio and dose of artemether-lumefantrine to account for metabolic differences in babies under 5kg. Infants under 5 kg can be affected by placental malaria, leading to poor birth outcomes, or contract malaria from the bite of an infected mosquito. The prevalence of the disease in this age and weight group is poorly understood, and it is therefore often misdiagnosed. Current antimalarials have not been developed specifically for infants weighing under 5 kg. There is no approved treatment available for them, and they are treated with tablets meant for children above 5 kg adjusted by weight2. Yet, these tiny patients handle drugs differently due to the immaturity of their metabolizing organs, which can lead to overdose and toxicity. Coartem <5 kg Baby provides optimized dosing specifically tailored to the needs of these vulnerable patients. If approved, the treatment will close a significant treatment gap. “Infants below 5 kg make up a critical neglected group, and developing antimalarials specifically suited to their needs is essential to malaria control efforts,” said Wiweka Kaszubska, Executive Vice President, Head of Product Development, MMV. “The success of the CALINA trial brings us one step closer to ensuring that all patients have access to appropriate and effective treatments.” “The CALINA trial is an example of the type of Europe-Africa collaboration we need to close malaria treatment gaps for vulnerable groups, and EDCTP is proud to be part of this endeavor,” said Pauline Beattie, Operations Manager and Scientific Advisor, EDCTP Association. This year's theme for World Malaria Day – Health Equity, Gender, and Human Rights – serves as a stark reminder of our collective responsibility to protect every child from malaria. It underscores the need to ensure that the youngest and most vulnerable among us also have access to the right treatment. About the CALINA studyPharmacokinetics, Safety, Tolerability and Efficacy of a New Artemether-lumefantrine Dispersible Tablet in Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria (CALINA) is an open-label, single-arm, multicenter phase II/III study in young infants < 5 kg with uncomplicated Plasmodium falciparum malaria, which evaluated the PK, safety, tolerability and efficacy of a new dose regimen (5mg:60mg). The study consists of a core segment (treatment and follow-up for 43 days) and long-term follow-up at 12 months of age to assess neurodevelopmental status. The trial was conducted in Burkina Faso, DRC, Kenya, Mali, Nigeria, and Zambia. The primary PK endpoint of the study was met for patients > 28 days of age. For neonates <= 28 days of age, although the sample size was too small for a conclusive statistical evaluation, the required value of the PK endpoint was also within the calculated interval. The key secondary endpoint of lumefantrine C168 concentration was also met for cohort 1 and within range for cohort 2. This indicates that the new dose regimen/formulation delivers exposures to artemether and lumefantrine proven to be safe and effective in paediatric patients of higher body weight. More information about the trial can be found here. DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. About MMVMMV is a leading product development partnership (PDP) in the field of antimalarial drug development and delivery. 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 and partners have built the largest portfolio of antimalarial R&D and access projects ever assembled, have brought forward 15 medicines that are treating patients. An estimated 15.4 million deaths have been averted by these MMV co-developed medicines. 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 help to ultimately eradicate this terrible disease. References World malaria report 2023 (who.int)WHO guidelines for malaria - 16 October 2023 (magicapp.org) # # # Novartis Media RelationsE-mail: media.relations@novartis.com Central North America Richard Jarvis+41 79 584 2326Michael Meo+1 862 274 5414Anja von Treskow+41 79 392 9697Marlena Abdinoor+1 617 335 9525Anna Schäfers+41 79 801 7267 Switzerland Satoshi Sugimoto+41 79 619 2035 Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com Central North America Isabella Zinck+41 61 324 7188Sloan Simpson+1 862 345 4440Nicole Zinsli-Somm+41 61 324 3809Jonathan Graham+1 201 602 9921Imke Kappes+41 61 324 8269Parag Mahanti+1 973 876 4912

Clinical StudyClinical Result

14 Dec 2023

·www.prnewswire.com

Fosun Pharma's Global Multi-Center Phase III Clinical Trial Project for A New Antimalarial Drug Receives 500 Million Japanese Yen Investment from GHIT Fund to Jointly Improve the Global Accessibility of Antimalarial Drugs

SHANGHAI, Dec. 14, 2023 /PRNewswire/ -- The Japan-based Global Health Innovative Technology Fund (GHIT Fund) announced today that it will invest approximately US$3.3 million (approximately 500 million yen[1]) in a global multicenter Phase III clinical trial project (the "Program") led by Fosun Pharma for a triple artemisinin combination drug (Artemether-Lumefantrine-Amodiaquine fixed-dose formulation) against malaria in Africa and Southeast Asia, to accelerate the development and commercialization of this new drug. The Project will be jointly conducted by Fosun Pharma, a major Chinese pharmaceutical and healthcare company, Marubeni, a leading Japanese integrated trading and investment business conglomerate, a Thailand-based research collaboration of universities, Mahidol-Oxford Tropical Medicine Research Unit (MORU), and the product development partnership Medicines for Malaria Venture (MMV), which provides technical support and market access expertise. This is the first time GHIT Fund has invested in a research project led by a Chinese pharmaceutical company. This drug candidate should have a significant public health benefit as it is expected to play an important role in the fight against artemisinin partial resistance (ART-R) which is now observed widely in the Greater Mekong Subregion (GMS) of Southeast Asia[2] and to some extent in several African countries, including Rwanda and Uganda. Importantly, the project includes the development of a co-formulated child-friendly version, given that most malaria cases are in children[3]. Malaria is an infectious parasitic disease transmitted by mosquitos that affects approximately 250 million people annually and was responsible for approximately 620,000 deaths in 20213. Infection in the African region constitutes 95% of the total global malaria cases, and children under the age of 5 account for 80% of all malaria deaths in this region. The GHIT Fund invests in innovative drug development with the aim of contributing to global health through facilitating collaboration between Japanese and global institutions' technology and innovation to address these neglected infectious diseases. Wen Deyong, CEO of Fosun Pharma, said, "We are very pleased to work with GHIT Fund to promote the clinical research on this antimalarial innovator drug. The collaboration will accelerate the launch of this new drug so as to actively respond to the threat of artemisinin partial resistance and partner drug resistance of Plasmodium falciparum parasites and save more lives from malaria. Fosun Pharma is committed to further improving the accessibility and affordability of antimalarial drugs through continuous innovation and our global operational capabilities, so as to continuously strive for a malaria-free world." Dr. Osamu Kunii, CEO of the GHIT Fund, said "We are very excited to have Marubeni and FOSUN PHARMA as our new product development partners. It is an important step forward to invest in the development of antimalarial drugs in late-phase clinical trials to advance commercialization. The number of malaria cases and deaths in children under 5 years old is an urgent issue. This investment will make a significant contribution to reducing the burden of malaria globally, especially among young children." The antimalarial drug independently developed by Fosun Pharma has been used to treat more than 60 million patients with severe malaria worldwide The artemisinin based antimalaria medicines originated from China have made significant contributions to global malaria prevention and control. In Sub-Saharan Africa alone, about 240 million people benefit from artemisinin-based combination therapies every year. The artesunate for injection (Artesun®) independently developed by Fosun Pharma is the first-line treatment of severe malaria for both adults and children recommended by the WHO since 2011. It has become a well-known Chinese innovator drug in Africa and the world. So far, Artesun® has been used to treat more than 60 million patients with severe malaria worldwide, most of whom were African children under five years old. In June 2023, the second-generation artesunate for injection (Argesun®) independently developed by Fosun Pharma was prequalified by the WHO (WHO-PQ), becoming the first injectable artesunate presented with a single solvent system approved by WHO-PQ. It greatly improves the convenience of clinical use and is particularly practicable for remote areas in Africa with backward medical conditions to save more lives. Up to now, the product has been registered and marketed in 18 countries. The deployment of Fosun Pharma's new generation Argesun® has further improved the accessibility of high-quality antimalarial innovator drugs in Africa, providing a convenient solution for primary medical institutions to treat sever malaria patients and save lives. Fosun Pharma was therefore recognized on Fortune 2023 China's Most Admired Company List. Effectively reduce the incidence rate of severe malaria in children from treatment to prevention As an innovation-driven global pharmaceutical and health industry group, Fosun Pharma has independently developed innovative antimalarial products covering malaria prevention and treatment, as well as the rescue of critically ill patients. From "treatment" to "prevention", Fosun Pharma continues to provide more prevention and treatment solutions for malaria patients, especially children. In August 2018, Fosun Pharma's SPAQ-CO® Disp (co-packed sulfadoxine-pyrimethamine dispersible tablets and amodiaquine dispersible tablets), for the prevention of malaria in children, was prequalified by WHO. Fosun Pharma has actively carried out community-oriented "Child Malaria Prevention Knowledge Popularization Projects" in 14 malaria-endemic countries in Africa. These projects aim to enhance local awareness of malaria prevention among African populations, thus helping to reduce the incidence of malaria and interrupt community transmission of the disease. By the end of June 2023, more than 245 million children in Africa had benefited from the "Seasonal Malaria Chemoprevention Program", for which SPAQ-CO® Disp is used as the core drug, effectively reducing the incidence of malaria in children under five years old in Africa. About GHIT Fund The GHIT Fund is a Japan-based international public-private partnership (PPP) fund that was formed between the Government of Japan, multiple pharmaceutical companies, the Bill & Melinda Gates Foundation, Wellcome, and the United Nations Development Programme (UNDP). The GHIT Fund invests in and manages an R&D portfolio of development partnerships aimed at addressing neglected diseases, such as malaria, tuberculosis, and neglected tropical diseases, which afflict the world's vulnerable and underserved populations. In collaboration with global partners, the GHIT Fund mobilizes Japanese industry, academia, and research institutes to create new drugs, vaccines, and diagnostics for malaria, tuberculosis, and neglected tropical diseases. About Fosun Pharma Founded in 1994, Shanghai Fosun Pharmaceutical (Group) Co., Ltd.* ("Fosun Pharma"; stock code: 600196. SH, 02196. HK) is a global innovation-driven pharmaceutical and healthcare industry group. Fosun Pharma directly operates businesses including pharmaceuticals, medical devices, medical diagnosis, and healthcare services. As a shareholder of Sinopharm Co., Ltd., Fosun Pharma expands its areas in the pharmaceutical distribution and retail business. Fosun Pharma is patient-centered and clinical needs-oriented. The company continuously enriches its innovative product pipeline through independent research and development, cooperative development, license-in, and in-depth incubation. Fosun Pharma improves the research and clinical development capabilities of FIC (First-in-class) and BIC (Best-in-class) new drugs as well as accelerates the R&D and launch of innovative technologies and products. Guided by the 4IN strategy (Innovation, Internationalization, Intelligentization, and Integration), Fosun Pharma will uphold the development model of "Innovation Transformation, Integrated Operation and Steady Growth", with the mission of creating shareholder values through strengthening its independent R&D and external cooperation and enriching its product pipelines, as well as promoting the global networks and enhancing operational efficiency. Fosun Pharma will actively promote the digital and physical business layout in the pharmaceutical and healthcare industry and is committed to becoming a first-class enterprise in the global pharmaceutical and healthcare markets. For more information, please visit our official website: . SOURCE Fosun Pharma

Phase 3Drug Approval

21 Sep 2023

·www.sciencedaily.com

New strategies reduce treatment failure in malaria by up to 81%

To slow artemisinin resistance and reduce treatment failures, an international research team investigated various drug policy interventions in Rwanda, where artemisinin resistance was first reported in 2020. Among other strategies, the team found that next-generation interventions such as triple ACTs (TACTs) -- which combine an artemisinin derivative with two partner drugs or which use a sequential course of one ACT formulation, followed by a different ACT formulation -- resulted in treatment failure counts that were at least 81% lower. Artemisinin-based combination therapies (ACTs) are the globally-accepted first-line treatments for malaria -- a mosquito-borne disease caused by the Plasmodium falciparum parasite that annually kills around 600,000 people, mostly children. Yet resistance to ACTs by P. falciparum has emerged in recent years in Africa, threatening their effectiveness. To slow this resistance and reduce treatment failures, an international research team led by Penn State investigated various drug policy interventions in Rwanda, where artemisinin resistance was first reported in 2020. Among other strategies, the team found that next-generation interventions such as triple ACTs (TACTs) -- which combine an artemisinin derivative with two partner drugs or which use a sequential course of one ACT formulation, followed by a different ACT formulation -- resulted in treatment failure counts that were at least 81% lower. Their results were published today (Sept. 21) in Nature Medicine. "The malaria drug-resistance situation in Rwanda is urgent," said Robert Zupko assistant research professor of biology, Penn State. "If we let things continue as is, artemisinin-resistant genotypes will begin to dominate by the end of this decade. Of the two dozen interventions we evaluated, we found that TACTs -- a treatment yet to be approved to treat malaria but undergoing clinical evaluations -- was projected to minimize both treatment failures and drug resistance." Dr. Aline Uwimana, head of case management at the Rwanda Biomedical Center and a senior author on the study, cautioned that waiting for optimal therapies may not be the best approach as resistance could soon be widespread. "Of the available and approved approaches that we evaluated for this study, there were several options using multiple first-line therapies, or MFT, that we could begin to put into place next year," Uwimama said. "This is likely the most feasible choice in the near term." Under an MFT strategy, multiple therapies are deployed at once and different patients get treated with different drugs. According to Maciej Boni, professor of biology, Penn State, the current situation in Rwanda is a repeat or "three-peat" of past malaria drug failures. Since the 1940s, multiple antimalarial drugs have been deployed worldwide, but the eventual development of drug resistance in the malaria parasite forced the withdrawal of all of them. In the 1990s, new artemisinin drugs were trialed and found to be effective, and by 2005 they were recommended worldwide, he said. The following year, Rwanda adopted the ACT artemether-lumefantrine (AL) as its first-line therapy for malaria, but by 2020, a mutation, known as 'pfkelch13 R561H', was shown to have emerged over the previous decade; the R561H mutation is associated with delayed clearance of the parasite in the presence of AL. "Studies indicate that the pfkelch13 R561H mutation is increasing, but there still may be a window of opportunity to delay its spread and avert high numbers of treatment failures," Boni said. "The World Health Organization has recommended that the Rwandan National Malaria Control Program begin considering strategies for mitigating the spread of pfkelch13 R561H." To address this recommendation, Zupko and Boni worked with the Rwandan National Malaria Control Program and the Rwanda Biomedical Centre to develop plans for slowing down the spread of artemisinin resistance in Rwanda. Specifically, they examined a range of possible drug policy interventions and their ability to reduce long-term treatment failures. These included replacing AL as the first-line therapy with another artemisinin drug, introducing multiple drugs to be used in combination and lengthening the dosing schedule for AL from a three-day course of treatment to up to a five-day course of treatment. Additionally, the researchers evaluated sequential therapy approaches -- in which one drug is given for a period of time followed by another -- and triple artemisinin combination therapies. The team modeled the impacts of these strategies on projected treatment failures and the frequency of the R561H mutation within the Plasmodium genome three, five and ten years into the future. "We found that lengthening courses of treatment, deploying multiple drugs and implementing custom rotation strategies all provide a benefit when compared to the currently recommended three-day course of AL," Zupko said. Specifically, the researchers found that extending the use of AL from three to five days and using multiple drugs simultaneously are two strategies that may hold treatment failure rates at or near 10%. In another study, which was published on July 29 in Nature Communications, the team looked more closely at triple artemisinin combination therapies (TACTs) in general African malaria settings. This work was done by two teams independently -- the Penn State team and a University of Oxford modeling team led by associate professor Ricardo Aguas -- to ensure that the results were not strongly influenced by the build and design of a single model. "TACTs have been shown in clinical trials to be effective and well tolerated by patients, and the fact that early TACT adoption may delay the emergence and spread of antimalarial drug resistance is a modeling result of vital importance," Boni said. Zupko noted that the results of the research underscore what is already known from historical experience -- drug resistance can spread rapidly once it is established. "It is important to quickly implement an antimalarial policy that contains the spread of artemisinin resistance, including the immediate introduction of TACTs," he said. Other Penn State authors on the paper include Tran Dang Nguyen, assistant research professor of biology; Thu Nguyen-Anh Tran, graduate student in biology; and Kien Trung Tran, postdoctoral scholar in biology. Others from the Rwanda Biomedical Centre include J. Claude S. Ngabonziza, division manager; Michee Kabera, director of epidemiology; and Aline Uwimana, director of case management. Haojun Li, recent Penn State graduate and current Columbia University graduate student, also is an author. The National Institutes of Health and Bill and Melinda Gates Foundation supported this research.

100 Deals associated with Artemether/Lumefantrine

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R&D Status

Approved

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Indication	Country/Location	Organization	Date
Acute Malaria	US	Novartis Pharmaceuticals Corp.	07 Apr 2009
Malaria	CN	KPC Pharmaceuticals, Inc.	01 Jan 1992

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Falciparum	Phase 3	KE	Novartis AG	01 Jul 2002
Malaria, Falciparum	Phase 3	NG	Novartis AG	01 Jul 2002
Malaria, Falciparum	Phase 3	TZ	Novartis AG	01 Jul 2002

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03453840 (Pubmed)	Phase 4	Malaria HIV \| 18S rRNA \| SBP1	303	3-day artemether-lumefantrine regimen	ojwuxfxtyg(axkfhjfpgy) = rnruorgzfs umtrsrwkcq (sbvmxehodf )	Positive	07 May 2024
				5-day artemether-lumefantrine regimen	ojwuxfxtyg(axkfhjfpgy) = pdicpufufc umtrsrwkcq (sbvmxehodf )
NCT04300309 (CALINA, GlobeNewswire) Manual	Phase 2/3	Malaria	-	artemether-lumefantrine	-	Positive	24 Apr 2024
ACTRN12623000344695 (Pubmed)	Phase 4	Malaria \| Infectious Diseases Second line Pfkelch13 \| Pfcrt \| Pfmdr-1 ... View more	357	Artemether-lumefantrine (AL)	itrbdfswaf(snpggfmokh) = uyebglmlhg rhpfqjbrpq (cqzhswwwon, 91.4 - 99.7)	-	03 Apr 2024
				Dihydroartemisinin-piperaquine (DP)	itrbdfswaf(snpggfmokh) = ajhqxjotcu rhpfqjbrpq (cqzhswwwon, 92.1 - 99.8)
NCT04041973 (Pubmed)	Not Applicable	-	1,480	Artemether-lumefantrine	cfqyvhlkxi(vmfqlexzmn) = Overall prevalence of adverse events was 1·9% (355 events in 18 806 doses) in the artemether-lumefantrine group and 1·1% (207 events in 19 132 doses) in the multivitamin group (p<0·0001) lhpmryucml (cnloavamwh ) View more	Positive	26 Sep 2022
				Antimalarial chemoprophylaxis (Multivitamin)
Pubmed	Not Applicable	Malaria	177	3-day AL regimen	lhofuscmuo(bepqsybsrv) = lqjiygttcf vntogzwcfs (xrgcfkmrlt ) View more	-	20 Sep 2022
				5-day AL regimen	lhofuscmuo(bepqsybsrv) = faizayyhvh vntogzwcfs (xrgcfkmrlt ) View more
NCT05060198 (Pubmed)	Not Applicable	Malaria	340	Artemether-Lumefantrine	tbbbanjzlq(gxmgfldwdj) = ugbfnfrjjz mpktdtgcxa (mfxrzmrmus, 80.9 - 93.3)	Positive	29 Aug 2022
				Dihydroartemisinin-Piperaquine	tbbbanjzlq(gxmgfldwdj) = comdzlccpv mpktdtgcxa (mfxrzmrmus, 86.9 - 96.4)
NCT03355664 (TACT-CV, CTgov)	Phase 3	Malaria, Falciparum	310	Artemether-lumefantrine+Primaquine (Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24)	ngitizctml(pzglbwvhaa) = fywatmzqgq ugtjecotzs (bbvvknwnqt, aaurdgqiyu - mztxxrmgll) View more	-	15 Jul 2022
				Artemether-lumefantrine+Primaquine+Amodiaquine (Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24)	ngitizctml(pzglbwvhaa) = sayfrdtfqg ugtjecotzs (bbvvknwnqt, hhfiahibyo - padrsgoock) View more
NCT03952650 (CTgov)	Phase 1/2	Malaria	252	PYR+PfSPZ (1a - Pilot/Safety: Dosing Interval on Days: 1)	dfolfviehi(tjlyfshjqg) = namqbalyaq owpapknamj (vebovaaujp, lvbbrhfkae - ibkfjahkaa) View more	-	12 Jul 2022
				PYR+PfSPZ (2a - Pilot/Safety: Dosing Interval on Days: 1)	dfolfviehi(tjlyfshjqg) = yvgxgthamq owpapknamj (vebovaaujp, ichhohfbtu - agtkrurhis) View more
ACTRN12616001422415 (Pubmed \| Malar J)	Phase 4	Malaria	994	Artemether-lumefantrine (AL)	njzdmabkbz(ycpwupfodw) = xquekzzozu pmtwarhhzb (kepusantlr )	-	02 May 2022
				Artesunate-amodiaquine (ASAQ)	njzdmabkbz(ycpwupfodw) = okxwfjoqrh pmtwarhhzb (kepusantlr )
NCT03355664 (TACT-CV, Pubmed \| Lancet Infect Dis) Manual	Phase 3	Malaria, Falciparum First line	310	Artemether+artemether-lumefantrine	hmmmfanuql(eappweeonz) = bagwjgtjsq pbsnkpliez (vlrjcqquso ) View more	Positive	08 Mar 2022
				Artemether+artemether-lumefantrine+Amodiaquine	hmmmfanuql(eappweeonz) = ebdxnrrqdj pbsnkpliez (vlrjcqquso ) View more

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