Present clinical trial, pharmacokinetic data of antiparasitic drug Tafenoquine: CDSCO panel tells GSK

New Delhi: Seeking justification for Phase III Clinical Trial waiver, the Subject Expert Committee (SEC) functional under the Central Drug Standard Organization (CDSCO) has directed GlaxoSmithKline (GSK) Pharmaceuticals to submit and present all clinical trial data for safety, efficacy, and pharmacokinetic (PK) data generated with the antiparasitic drug Tafenoquine Tablets.

This came when drug-maker GlaxoSmithKline Pharmaceuticals presented a proposal before the committee in line with the earlier recommendation, at the 101st SEC meeting for Antimicrobial & Antiviral held on 23.06.2021 & 24.06.2021 at CDSCO.

Tafenoquine is a long-acting 8-aminoquinoline, synthetic analogue of Primaquine with a half life of approx. 15days. The drug is approved in the USA and Australia.

Scientists at the Walter Reed Army Institute of Research discovered the above said drug in 1978 as a primaquine replacement that was more successful against relapsing vivax malaria. Tafenoquine was further developed collaboratively by GlaxoSmithKline and Medicines for Malaria Venture. On July 20, 2018, Tafenoquine was approved by the FDA.

Earlier, the Medical Dialogues Team had reported that Tafenoquine, approved by the Food and Drug Administration (FDA), was the first prophylactic agent to be approved in more than 18 years for the prevention of malaria in patients aged ≥18 years.

Tafenoquine acts by inhibiting hematin polymerization and inducing apoptotic like the death of the parasite. It is active against all stages of Plasmodium species and also causes red blood cell shrinkage in vitro.

Previously, at the 56th SEC meeting for Antimicrobial & Antivirals, GlaxoSmithKline Pharmaceuticals had presented their proposal for the manufacture and marketing of Tafenoquine Tablets 150mg for the radical cure (prevention of relapse) of P. vivax, as well as clinical trial data generated through global clinical trials, including Phase 2b trials, in which India was one of the participating countries. Further, the drug maker had mentioned that in the phase 2b trial, 57 Indian patients were involved.

The advantages and disadvantages of Tafenoquine were thoroughly discussed during the above-mentioned meeting, with GSK stating that the medication had the advantage of just requiring a single dose for radical cure, as compared to the 14-day therapy required by Primaquine.

Furthermore, it was stated that both Tafenoquine and Primaquine have been reported to cause hemolytic anaemia in G6PD deficient individuals, prompting the recommendation of a G6PD test. In the event of unintentional usage of the medicine in G6PD deficient patients, tafenoquine has a disadvantage in that the drug's impact will stay in the body for many days after a single dose.

However, at the 56th SEC meeting for Antimicrobial & Antiviral, after detailed deliberation, the committee recommended that the firm should submit the detailed strategy/modalities that should be followed to address the concerns for further review, including the requirement for clinical trial. The committee further suggested that the CDSCO should consult the National Vector Borne Disease Control Program (NVBDCP) on the proposal.

In continuation, at the 62nd SEC meeting for Antimicrobial & Antivirals, considering the opinion of the National Vector Borne Disease Control Programme, the committee recommended the firm to submit a protocol for assessing the feasibility of making the drug available in India in light of concerns relating to G6PD deficiency.

Accordingly, at the next SEC meeting, the drug maker GSK presented a proposal for a feasibility study protocol entitled "Implementation of Quantitative Glucose-6-Phosphate Dehydrogenase Testing and Tafenoquine for Plasmodium vivax Radical Cure in India", where the committee noted the following points:

1. The feasibility study was to be implemented in peripheral public health care settings.

2. There was no plan mentioned in the presented protocol for assessing and monitoring adverse events after administration of the drug.

3. The protocol does not mention the factors/end points on the basis of which continuation to the next phase would be decided.

In response to the feasibility study protocol, the committee requested that the company submit a Phase III clinical trial protocol as well as a revised feasibility protocol for the committee's assessment.

Accordingly, at the latest SEC committee meeting, following GSK's proposal for Tafenoquine Tablets 150 mg, after detailed deliberation, the committee recommended that the firm submit and present all clinical trial data for safety, efficacy, and PK data generated with the drug so far, along with justification for waiver of Phase III clinical trial for further consideration by the committee.