In an unusual action, the U.S. Food and Drug Administration (FDA) asked an advisory committee to meet twice in two weeks this past summer to discuss nearly identical products with similar indications from two different pharmaceutical companies. During their vote, committee members noted the global need for additional agents for the prevention of malaria.
“The World Health Organization estimates more than 200 million cases of malaria worldwide with more than 400,000 deaths per year.”
The Antimicrobial Drugs Advisory Committee (AMDAC) voted that sponsor GlaxoSmithKline had provided adequate evidence of the safety and substantial evidence of the efficacy of new drug application (NDA) 210795 for Krintafel (tafenoquine succinate) on July 12. The AMDAC echoed this vote in support of NDA 210607 for Arakoda (tafenoquine) by 60 Degrees Pharmaceuticals on July 26.
The FDA moved quickly to approve Krintafel on July 20 — just eight days after the advisory committee meeting — and Arakoda on August 9, two weeks following its advisory committee meeting. While advisory committees inform the FDA’s decision-making, the agency is not obligated to follow their voting recommendations, but it may do so once all information is considered.
Tafenoquine is an analog of primaquine which was first developed by the U.S. Army nearly 40 years ago, then licensed to private companies. The Walter Reed Army Institute of Research collaborated with GlaxoSmithKline for the Krintafel NDA; U.S. Army Medical Materiel Development Activity partnered with 60 Degrees Pharmaceuticals for the Arakoda NDA.
Krintafel is a 150 mg antimalarial tablet indicated for the radical cure (prevention of relapse) of Plasmodium vivax (P. vivax) malaria in patients aged ≥16 years who are receiving appropriate antimalarial therapy for acute P. vivax infection. Krintafel is not indicated for the treatment of acute P. vivax malaria. The drug is administered as a single dose of 300 mg (i.e., two 150 mg tablets), administered on day 1 or day 2 of chloroquine therapy. It was the first drug approved for the prevention of relapse of P. vivax malaria in ≥60 years.
Arakoda is indicated for the prevention of malaria (against all species of Plasmodium, including P. vivax and P. falciparum) in adults for ≤6 months of continuous dosing. The drug is approved for prophylaxis, while in the endemic region and post-exposure: that is, administration as a 200 mg single dose (i.e., two 100 mg tablets) once daily during the three days before travel to a malarious area, then two 100 mg tablets once weekly during travel for up to six months. A final dose (i.e., two 100 mg tablets) is given during the week following departure from the malarious area. Arakoda’s proposed indication differs from Krintafel’s in that the former is for prevention, while the latter is for prevention of relapse (see Table 1 for a comparison of the two products).
Different routes to expedited FDA approval
To support innovation in fighting serious, rare and life-threatening diseases, the FDA may grant fast-track designation, breakthrough therapy designation, accelerated approval, priority review designation and orphan drug designation to developers of drugs and biologics, as outlined on the FDA website.
The treatment must provide meaningful therapeutic benefit over existing treatments; this process is also applicable to diseases for which there is no existing therapy. Details about the accelerated approval process are detailed in the FDA’s Guidance for Industry: Expedited Programs for Serious Conditions – Drugs and Biologics (Final), published in May 2014. The FDA granted fast-track and priority review status to 60 Degrees Pharmaceuticals for its proposed indication, whereas sponsor GlaxoSmithKline received breakthrough therapy and orphan drug designation for its formulation of tafenoquine succinate.
|Table 1. Tafenoquine Indications|
Radical cure of P. vivax malaria
Prevention of P. vivax and P. falciparum
|Sponsor||GlaxoSmithKline Intellectual Property Development Ltd.||60 Degrees Pharmaceuticals LLC|
|Population||Symptomatic P. vivax patients||Malaria naïve, asymptomatic adults at risk of contracting malaria|
|Tablet strength||150 mg||100 mg|
|Dosing regimen||2 × 150 mg||200 mg × 3 load then 200 mg once weekly during travel|
|Duration||Single dose||Up to six months|
|U.S. patients||<1,000 cases per year||≥250,000 prescriptions per year|
|FDA status||Orphan drug/breakthrough therapy||Fast track/priority review|
Source: 60 Degrees Pharmaceuticals.
According to the Centers for Disease Control and Prevention, the development of resistance to drugs poses one of the greatest threats to malaria control and results in increased malaria morbidity and mortality. P. falciparum and P. vivax species have different drug-resistance patterns in differing geographic regions. Malaria hospitalizations and deaths are largely preventable through the use of personal protective measures, adherence to correct chemoprophylactic regimens, and medical care that ensures rapid and correct diagnosis and treatment.
Malaria is a life-threatening disease transmitted through the bite of an infected mosquito. The World Health Organization estimates more than 200 million cases of malaria worldwide with more than 400,000 deaths per year. In areas with high transmission of malaria, children under 5 years of age are particularly susceptible to infection, illness and death; 70% of all malaria deaths occur in this age group.
This article leverages data from Cortellis Regulatory Intelligence and the Incidence and Prevalence Database, which includes epidemiological data on malaria and more than 4,000 other diseases.
Editor’s Note: A version of this article was originally published in the Journal for Clinical Studies. Read here.
Photo credit: Centers for Disease Control and Prevention