FDA Drug Approvals: Primary Care — Year in Review 2018

Mary L Windle, PharmD


January 15, 2019

Other New Antimicrobials

Xofluza (baloxavir marboxil)

Baloxavir marboxil was approved by the FDA in October 2018 for the treatment of influenza in adults and adolescents aged 12 years or older as a single, weight-based oral dose for use within 48 hours of symptom onset. It is a prodrug that inhibits cap-dependent endonuclease, an enzyme specific to influenza, resulting in inhibition of viral replication. In clinical trials, single-dose baloxavir was safe and effective in treating patients with uncomplicated influenza. It is active against influenza A and B, including strains resistant to neuraminidase inhibitors.

Approval of baloxavir marboxil was based on the CAPSTONE-1 trial (n=1436). Patients aged 12-64 years were randomized to receive baloxavir, oseltamivir, or placebo. Of the 1064 patients included in the intention-to-treat infected population, the median time to alleviation of symptoms was 53.7 hours in the baloxavir group compared with 80.2 hours for placebo (P <.001). Similar results were observed with oseltamivir compared with placebo. Additionally, the baloxavir group had a significant decrease in viral load after 1 day of treatment compared with both the placebo (P <.05) and oseltamivir (P <.05) groups. It is undetermined whether the rapid drop in viral load decreases the risk of virus transmission. (N Engl J Med. 2018 Sep 6;379(10):913-923)

Krintafel, Arakoda (tafenoquine)

In July 2018, the FDA approved tafenoquine, an antiplasmodial 8-aminoquinoline derivative indicated for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged 16 years or older who are receiving appropriate antimalarial therapy for acute P vivax infection. The drug is active against all stages of the P vivax life cycle. Tafenoquine is administered as a single oral dose on the first or second day of appropriate antimalarial therapy (eg, chloroquine) for acute P vivax malaria. Approval was based on an international program of over 4000 participants.

In one of the clinical trials, 329 patients were randomly assigned to a treatment group (chloroquine plus tafenoquine 50 mg [n=55], 100 mg [n=57], 300 mg [n=57], 600 mg [n=56]; or chloroquine plus primaquine [n=50]; or chloroquine alone [n=54]). Relapse-free efficacy at 6 months was 89.2% with tafenoquine 300 mg and 91.9% with tafenoquine 600 mg, as compared to 37.5% with chloroquine alone. The results showed a significantly improved treatment difference, compared with chloroquine alone, of 51.7% (P <.0001) with tafenoquine 300 mg and 54.5% (P <.0001) with tafenoquine 600 mg. (Lancet. 2014 Mar 22;383(9922):1049-58)

In August 2018, tafenoquine gained a second indication for adults aged 18 years or older as prophylaxis when traveling to malarious areas. For this indication, the 100-mg tablet (Arakoda) is administered as a loading dose before traveling to an endemic area, a maintenance dose while in a malarious area, and then a terminal prophylaxis dose in the week exiting the area.

Aemcolo (rifamycin)

Rifamycin is an oral nonabsorbable ansamycin antibiotic indicated for traveler's diarrhea caused by noninvasive strains of Escherichia coli not complicated by fever or blood in the stool. It acts by inhibiting the beta-subunit of bacterial DNA-dependent RNA polymerase, blocking one of the DNA transcription steps; this results in bacterial synthesis inhibition and, consequently, bacterial growth.

Approval was based on data from two randomized, multicenter, controlled phase 3 clinical trials. In both trials, rifamycin was dosed at 388 mg twice daily for 3 days. Rifamycin demonstrated superiority over placebo (P=.0008) and was noninferior to ciprofloxacin (P=.0011) for the primary endpoint (time to last unformed stool). (Aemcolo (rifamycin) prescribing information)


Moxidectin is an antiparasitic drug approved by the FDA in June 2018 to treat onchocerciasis in patients aged 12 years or older. The World Health Organization initiated clinical trials for use in onchocerciasis in 2009. Moxidectin is closely related to ivermectin, but it has a more sustained reduction in microfilarial levels. Its plasma half-life is 20-43 days and, thereby, reduces and maintains low skin microfilarial density effectively. FDA approval was based on a double-blind, parallel-group, superiority trial (n=1472) that compared moxidectin (8 mg PO once) with ivermectin (150 mcg/kg PO once). The trial took place in Ghana, Liberia, and the Democratic Republic of the Congo. Results showed that skin microfilarial loads (ie, parasite transmission reservoir) were lower from month 1 to month 18 after moxidectin treatment than after ivermectin treatment, with an 86% difference at month 12. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress toward elimination. (Lancet. 2018 Oct 6;392(10154):1207-1216)

TPOXX (tecovirimat)

Tecovirimat is an antiviral protein inhibitor indicated for human smallpox disease caused by variola virus in adults and children who weigh more than 13 kg. It is available through the US government's Strategic National Stockpile.

Effectiveness of tecovirimat against smallpox was established by studies in animals infected with viruses closely related to variola virus, which demonstrated higher survival rates compared with placebo. (N Engl J Med. 2018 Jul 5;379(1):44-53)


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