Krintafel (tafenoquine) / GSK, Medicines for Malaria Venture, 60° Pharma - LARVOL DELTA

Piloting the options assessment toolkit with national malaria programme leaders from the Asia-Pacific countries: a meeting report. (PubMed, Malar J) - "Plasmodium vivax malaria remains a major challenge in the Asia-Pacific region, where National Malaria Programmes (NMPs) will need to determine optimal radical cure strategies given the availability of novel options, such as high-dose primaquine and tafenoquine. Overall, the OAT was well received as a tool for initiating policy discussions on P. vivax radical cure. The OAT represents an important step toward accelerating evidence-based policy change in malaria-endemic countries, with further refinements enhancing its utility."

Journal • Infectious Disease • Malaria

Co-design of a routine clinical review to improve the safety of high dose radical cure treatment for Plasmodium vivax malaria: findings from Cambodia and Ethiopia. (PubMed, Malar J) - "Identifying how clinical review visits could be adapted to local settings is important and can be achieved through co-creation. Collaboration has the potential to enable quality of care and patient safety. Suitable ways of reinforcing this relational infrastructure are required to optimize case management of patients."

Journal • Infectious Disease • Malaria

Vivax Elimination With Tafenoquine (VET) Study (clinicaltrials.gov) - P4 | N=1000 | Active, not recruiting | Sponsor: Shoklo Malaria Research Unit | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Malaria

ACTQ: ACT vs CQ With Tafenoquine for P. Vivax Mono-infection (clinicaltrials.gov) - P4 | N=606 | Recruiting | Sponsor: Shoklo Malaria Research Unit | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Feb 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Infectious Disease • Malaria

FocaL mass drug Administration for Plasmodium vivax Malaria Elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru. (PubMed, Res Sq) - P3 | "The fMDA regimen will include 25mg/kg chloroquine (CQ) plus a single 300mg dose of tafenoquine (TQ) for individuals age ≥16 years, and 25mg/kg of CQ plus 7 days of 0.5mg/kg/day of primaquine (PQ) if younger. Trial registration Clinicaltrials.gov NCT05690841. This trial was registered on 09 January 2023."

Journal • Hematological Disorders • Infectious Disease • Malaria • Metabolic Disorders

Prospective observational study to assess the feasibility and safety of appropriate Plasmodium vivax radical cure with tafenoquine or primaquine after quantitative G6PD testing during pilot implementation in Thailand. (PubMed, BMJ Glob Health) - "Point-of-care quantitative G6PD testing prior to appropriate tafenoquine or primaquine administration was operationally feasible within the Thailand health system, with no concerning adverse events, supporting implementation of this treatment algorithm in areas of active P. vivax transmission."

Journal • Observational data • Hematological Disorders • Infectious Disease • Malaria

Repositioning antimalarial drugs as anticancer agents: focus on Tafenoquine. (PubMed, Exp Cell Res) - "Furthermore, we provide the first evidence that one antimalarial, Tafenoquine (LD50=9.6μM in HCT116 cells), is capable of decreasing viability with an efficacy comparable to Etoposide (LD50=15.2μM in HCT116 cells) Further, Tafenoquine induces apoptosis and increases the expression of genes involved in cell cycle arrest and cell death. We also show that cells are sensitized to the apoptotic effects of Tafenoquine following depletion of the heme oxygenase 1 (HMOX-1) gene. Collectively, our studies confirm that antimalarial compounds hold the potential for use as anticancer agents and provide the first evidence to detail the potent efficacy of Tafenoquine against cancer cells in culture."

Journal • Infectious Disease • Oncology • HMOX1

Geoff Dow, PhD, Infectious Disease Product Development Expert, to Discuss Babesiosis at Healing Lyme Summit, April 15-21 (GlobeNewswire) - "Dr. Dow will also outline the purpose and status of two active clinical trials sponsored by 60 Degrees Pharmaceuticals...which are evaluating the efficacy and safety of tafenoquine in treating severe babesiosis and persistent disease in immunosuppressed patients."

Clinical • Infectious Disease

Sixty Degrees Pharmaceuticals Announces Patent License Agreement to Advance Development of Tafenoquine for Babesiosis Treatment and Prevention with Yale School of Medicine and Yale School of Public Health (GlobeNewswire) - "60 Degrees Pharmaceuticals, Inc...today announced the signing of a Patent License Agreement with Yale School of Medicine and Yale School of Public Health to jointly advance the development and commercialization of tafenoquine for the treatment and prevention of babesiosis....The agreement follows initiation of collaboration between researchers from both organizations to study the activity of tafenoquine against babesiosis, a serious tick-borne disease caused by microscopic parasites that infect red blood cells."

Commercial • Infectious Disease

Drug-induced hearing loss: a real-world pharmacovigilance study using the FDA adverse event reporting system database. (PubMed, Hear Res) - "On the whole, acetylsalicylic acid was the most frequently reported potential ototoxic drug, followed by levothyroxine sodium, adalimumab, omeprazole, and ergocalciferol...In risk signal detection, 432 of 1300 drugs exhibited potential ototoxic risk, in which tafenoquine showed the strongest statistical correlation with hearing impairment, followed by teprotumumab, amyl nitrite, potassium iodide, and paromomycin. Among main drug classes, antibacterials for systemic use was the drug class contained the maximum number of drugs with positive ototoxic risk signals, followed by psychoanaleptics, agents acting on the renin-angiotensin system, antineoplastic agents, and analgesics. In conclusion, our study summarized a comprehensive drug list containing 1300 reported potential ototoxic drugs in the FAERS database and profiled their ototoxicity risk characteristic from the aspect of reporting frequency and risk signal strength, which can provide reference for clinical medical..."

Adverse events • Journal • Real-world evidence • Oncology • Otorhinolaryngology • Pain

Efficacy of tafenoquine in dogs naturally infected with Babesia gibsoni. (PubMed, J Vet Med Sci) - "However, their symptoms improved after two more doses of tafenoquine. Although recurrence could not be prevented, tafenoquine might be a treatment against canine babesiosis."

Journal • Infectious Disease

Improved genetic screening with zygosity detection through multiplex high-resolution melting curve analysis and biochemical characterisation for G6PD deficiency. (PubMed, Trop Med Int Health) - "Accurate diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is crucial for relapse malaria treatment using 8-aminoquinolines (primaquine and tafenoquine), which can trigger haemolytic anaemia in G6PD-deficient individuals. Biochemical and structural characterisation revealed that these variants significantly reduced catalytic activity by destabilising protein structure, particularly in the case of the Radlowo mutation. The refinement of these high-resolution melting assays presents a highly accurate and high-throughput platform that can improve patient care by enabling precise diagnosis, supporting genetic counselling and guiding public health efforts to manage G6PD deficiency-especially crucial in malaria-endemic regions where 8-aminoquinoline therapies pose a risk to deficient individuals."

Journal • Hematological Disorders • Infectious Disease • Malaria • Metabolic Disorders

Differential ex vivo susceptibility of Plasmodium malariae and Plasmodium falciparum clinical isolates from Ghana and Mali to current and lead discovery candidate antimalarial drugs. (PubMed, Microbiol Spectr) - "In Ghana, the susceptibility of the two species to most of the current antimalarial drugs was comparable, except for artemether, sulfadoxine, and atovaquone, for which the drugs were less potent against P. malariae than P. falciparum (7.12 vs 2.15 nM, 25.72 vs 7.86 nM, and 10.38 vs 2.51 nM, respectively). In Mali, quinine was significantly more potent against P. malariae than P. falciparum (18.35 and 26.84 nM), and tafenoquine was less potent against P. malariae than P. falciparum (5.50 and 2.85 nM). Among the candidate drugs, except INE963, whose inhibitory potency was comparable between both species, the other compounds significantly inhibited P. malariae more than P. falciparum...However, in Mali, chloroquine resistance appeared to have affected the suitability of quinine-based compounds for non-falciparum malaria treatment. Therefore, additional studies are required to establish the efficacy of artemether-lumefantrine for the treatment of P. malariae..."

Journal • Preclinical • Infectious Disease • Malaria

An observational pilot study of an active surveillance tool to enhance pharmacovigilance in Brazil. (PubMed, Malar J) - "This observational pilot study provides insights into how digital reporting tools such as Seta can enhance pharmacovigilance in remote areas and build upon existing signal detection methodologies. Twenty-five AEs or pregnancies were reported to ANVISA that were unlikely to have been reported otherwise."

Adverse events • Journal • Infectious Disease • Malaria

Repurposing tafenoquine as a potent antifungal agent against Candida haemulonii sensu stricto. (PubMed, J Antimicrob Chemother) - "The findings of this study highlight tafenoquine's potential as a promising candidate for antifungal drug repurposing, especially against C. haemulonii sensu stricto. Its effectiveness in inhibiting fungal growth and biofilm formation underscores its viability for further clinical development as a novel antifungal therapy."

Journal • Hematological Disorders • Infectious Disease

PBPK-Led Assessment of Antimalarial Drug Concentrations in Breastmilk: A Strategy for Optimal Use of Prediction Methods to Guide Decision Making in an Understudied Population. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Physiologically based pharmacokinetic (PBPK) modeling was used to predict milk-to-plasma (M/P) ratios, infant daily doses (IDD) and relative infant doses (RID) for five antimalarials with clinical lactation data (chloroquine, pyrimethamine, piperaquine, mefloquine and primaquine)...RID was  10% for lumefantrine and tafenoquine. For atovaquone, RID was > 10% with Model 1 but not Model 2...These prediction methodologies can be used, alongside any licensed dosing information for < 1 year-olds, to evaluate whether a clinical lactation study is necessary and to inform drug label or policy recommendations. The ultimate goal is to better inform optimal treatment for lactating women supporting malaria eradication."

Journal • Infectious Disease • Malaria

Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics. (PubMed, Lancet Infect Dis) - "Substantial reductions in prevalence as measured by PCR were predicted with primaquine and tafenoquine regimens if these could be implemented with high coverage and adherence. The benefits of preventing P vivax relapses need to be balanced against the risks of inducing severe haemolysis in patients with G6PD deficiency."

Journal • Hematological Disorders • Infectious Disease • Metabolic Disorders

60 Degrees Pharmaceuticals Enrolls First Patient in Tafenoquine Expanded Access Clinical Study for Persistent (B. microti) Babesiosis (GlobeNewswire) - "60 Degrees Pharmaceuticals, Inc...announced today that the first patient has been enrolled in NCT06478641, an expanded access clinical study intended to confirm the activity of tafenoquine in treating patients with persistent babesiosis who have failed standard of care treatment and are at high risk of experiencing a relapse."

Trial status • Infectious Disease

Assessing tafenoquine implementation in Brazil: a qualitative evaluation of perceptions of healthcare providers and Plasmodium vivax patients (QualiTRuST Study). (PubMed, Malar J) - "Single-dose TQ for P. vivax malaria in Brazil's Amazon region was positively received by HCPs and patients. Positive perceptions of the medication may aid in improving patient adherence to malaria treatment, thereby reducing malaria recurrences. The findings underscore the importance of adaptive training to optimize P. vivax radical cure implementation."

Journal • Observational data • Hematological Disorders • Infectious Disease • Malaria • Metabolic Disorders

An Interventional Study to Compare the Efficacy and Safety of Tafenoquine (TQ) and Primaquine (PQ) When Either Are Taken Together With Chloroquine (CQ) for the Treatment of P. Vivax Malaria in Indian Participants Aged 2 Years and Older (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Malaria • Pediatrics

Vivax Elimination With Tafenoquine (VET) Study (clinicaltrials.gov) - P4 | N=1000 | Not yet recruiting | Sponsor: Shoklo Malaria Research Unit | Trial completion date: Sep 2025 ➔ Dec 2025 | Initiation date: Oct 2024 ➔ Jan 2025 | Trial primary completion date: Sep 2025 ➔ Dec 2025

Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Malaria

Pharmacokinetic and Pharmacodynamic Modeling of Monthly Tafenoquine in Healthy Vietnamese Volunteers for Malaria Prophylaxis and Elimination (ASTMH 2024) - "LCMS and AE analysis is ongoing for all participants. PK/PD modeling will be reported for AEs, TQ dose and regimen optimization."

Clinical • PK/PD data • Infectious Disease • Malaria

Operational feasibility of P. vivax radical cure after G6PD testing in Thailand (ASTMH 2024) - "This study evaluated the operational feasibility of providing appropriate radical cure with chloroquine (CQ) as blood stage treatment and either primaquine (PQ) or tafenoquine (TQ), the two 8-aminoquinolines registered to clear liver hypnozoites, after quantitative G6PD point-of-care testing in Thailand. Provision of appropriate radical cure with TQ single dose, daily or weekly PQ following quantitative G6PD testing was operationally feasible within Thailand’s public health system, without safety concerns. These results support the implementation of this treatment algorithm in areas of active P. vivax transmission for accelerating malaria elimination and preventing the re-establishment of transmission."

Late-breaking abstract • Anemia • Hematological Disorders • Infectious Disease • Malaria

Exposure to malaria prophylactic medication prescriptions during pregnancy in women receiving care in the US Military Health System from 2011-2023 (ASTMH 2024) - "Exposure was defined by prescription for mefloquine, chloroquine, doxycycline, tafenoquine, primaquine and/or atovaquone/proguanil with days of supply overlapping with pregnancy. As the proportion of women in the US military continues to increase, so too will the need for safe and efficacious chemoprophylaxis options for use during pregnancy. Further study of maternal, fetal and infant outcomes of pregnancies exposed to atovaquone-proguanil, considering duration and trimester of exposure, is warranted."

Clinical • Late-breaking abstract • Infectious Disease • Malaria

Aseptic, purified, vialed Plasmodium vivax sporozoites for controlled human malaria infection (ASTMH 2024) - "Primaquine and tafenoquine are the only licensed drugs that target Pv hypnozoites, but cause life threatening acute hemolytic anemia in patients with G6PD deficiency. We expect PvSPZ Challenge will similarly provide the larger malaria community with a radically enhanced tool to assess anti-Pv interventions, as a safe quality-controlled reagent with minimal variability in potency, that is logistically simpler to administer, not subject to geographical limitations for application, compared to mosquito bite CHMI. The characteristics of the SPF Sb, aseptic mosquito infections, and GMP-produced PvSPZ will be presented."

Anemia • Hematological Disorders • Infectious Disease • Malaria • Metabolic Disorders