Tafenoquine for the treatment of Plasmodium vivax malaria

Figures & data

Figure 1. Chemical structure of primaquine and tafenoquine.

Table 1. Key TFQ clinical efficacy studies

Study	Design	Study period	Location	Treatment allocation	Recurrence-free at 6 months, n/N (%)
DETECTIVE Phase 2	Randomized, double-blind, dose-ranging trial	2011–2013	Brazil, Peru, India, Thailand	1. CQ + TFQ (50 mg) 2. CQ + TFQ (100 mg) 3. CQ + TFQ (300 mg) 4. CQ + TFQ (600 mg) 5. CQ + PQ 6. CQ only	1. 29/55 (53%) 2. 29/57 (51%) 3. 48/57 (84%) 4. 43/56 (77%) 5. 34/50 (68%) 6. 21/54 (39%)
DETECTIVE Phase 3	Randomized, active-controlled, double-blind trial	2014–2016	Brazil, Cambodia, Ethiopia, Peru, Philippines, Thailand	1. CQ + TFQ (300 mg) 2. CQ + PQ 3. CQ + placebo	1. 155/260 (60%) 2. 83/129 (64%) 3. 35/133 (26%)
GATHER Phase 3	Randomized, active-controlled, double-blind trial	2015–2016	Brazil, Colombia, Peru, Thailand, Vietnam	1. CQ + TQ (300 mg) 2. CQ + PQ	1. 112/166 (76%) 2. 60/85 (71%)

Note: PQ arms all used 3.5 mg/kg total dose over 14 days (15 mg daily for 14 days), or low dose PQ

Figure 2. Efficacy of TFQ (x-axis) across radical cure trials (panels) and populations (y-axis). Shapes represent the method used to report efficacy of TFQ in preventing recurrences at 6-month follow. Colors represent the regimen used. Shape sizes represent the corresponding sample size. By region, study sites of the Phase 3 DETECTIVE trial were Ethiopia (Africa), Cambodia, Philippines, and Thailand (Asia), and Brazil and Peru (South America). By region, study sites of the Phase 3 GATHER trial were Thailand and Vietnam (Southeast Asia), and Brazil, Colombia and Peru (South America). Except for Phase 3 GATHER, where reported estimates were from Kaplan-Meier (KM) analysis, efficacy was estimated as proportion of patients free from recurrence at 6 months by Intention-To-Treat (ITT) analysis, or by Per-Protocol (PP) if ITT was not reported for the comparisons.

Drug Summary Box

Drug name	Tafenoquine (WR 238,605)
Phase	Launched
Indication	Prophylaxis of malaria Radical cure of P. vivax malaria
Pharmacology description	DNA inhibitor Viral replication inhibitor.
Route of administration	Oral route
Chemical Structure
Pivotal trials	DETECTIVE (phase 2, 3), GATHER (phase 3)