FDA Approvals, Highlights, and Summaries: Infectious Disease

February 27, 2020

Ervebo (Ebola Zaire vaccine)

Ebola Zaire vaccine is a live recombinant viral vaccine consisting of a vesicular stomatitis virus (VSV) backbone deleted for the VSV envelope glycoprotein and substituted with the envelope glycoprotein of the Zaire ebolavirus (Kikwit 1995 strain).

In the Ring vaccination study that vaccinated patients during the 2014 outbreak in the Republic of Guinea, results among the people who received the vaccine showed no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases 10 days or more after vaccination among those who did not receive the vaccine.

Lancet. 2017 Feb 4;389(10068):505-518

Ervebo Prescribing Information

Jynneos (smallpox and monkeypox vaccine)

Smallpox and monkeypox vaccine is an attenuated, live, nonreplicating vaccine for immunization of adults at high risk for smallpox or monkeypox infection. Approval was determined in a clinical study comparing the immune responses in study participants who received either Jynneos or ACAM2000, an FDA-approved vaccine for the prevention of smallpox. The study included approximately 400 healthy adults, aged 18-42 years, who had never been vaccinated for smallpox. Half of the study participants received 2 doses of Jynneos administered 28 days apart, and half received 1 dose of ACAM2000. The group vaccinated with Jynneos had an immune response that was not inferior to immune responses to ACAM2000.

Jynneos prescribing information

Fetroja (cefiderocol)

Cefiderocol is a cephalosporin antibiotic with activity against gram-negative aerobic bacteria. Cefiderocol functions as a siderophore and binds to extracellular free ferric iron. In addition to passive diffusion via porin channels, cefiderocol is actively transported across the outer cell membrane of bacteria into the periplasmic space using a siderophore iron uptake mechanism. It is indicated to treat complicated urinary tract infections, including pyelonephritis, caused by susceptible gram-negative microorganisms in adults who have limited or no alternative treatment options.

Fetroja prescribing information

Xenleta (lefamulin)

Lefamulin is a first-in-class pleuromutilin antibacterial. It inhibits bacterial protein synthesis through interactions (hydrogen bonds, hydrophobic interactions, and Van der Waals forces) with the A- and P-sites of the peptidyl transferase center (PTC) in domain V of the 23s rRNA of the 50S subunit. It is indicated for adults with bacterial community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, or Chlamydia pneumoniae. It is administered twice daily as either an intravenous infusion or an oral tablet. Approval was based on LEAP 1 and 2 trials.

In LEAP 1, patients (n=551) were randomized to either lefamulin 150 mg IV q12h or moxifloxacin 400 mg IV q24h. After 6 doses, patients could be switched to the oral study drug if prespecified improvement criteria were met. If methicillin-resistant S aureus was suspected, linezolid or placebo was added to moxifloxacin or lefamulin, respectively. Lefamulin was noninferior to moxifloxacin for early clinical response. Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin.

Clin Infect Dis. 2019 Feb 4

The LEAP 2 study (n=738) found oral lefamulin 600 mg q12h for 5 days was noninferior to moxifloxacin 400 mg/day for 7 days for treating bacterial CAP.

Presented at IDWeek 2018 Oct 4. San Francisco, CA


Pretomanid, a nitroimidazooxazine, is indicated for adults with extensively drug-resistant, treatment-intolerant, or nonresponsive multidrug-resistance tuberculosis. Pretomanid kills actively replicating Mycobacterium tuberculosis by inhibiting mycolic acid biosynthesis, thereby blocking cell-wall production. Efficacy was primarily demonstrated in a study of 109 patients who were treated with pretomanid plus bedaquiline and linezolid. Of the 107 patients who were evaluated 6 months after the end of therapy, 95 (89%) had successful treatment, far exceeding success rates of available treatments.

Pretomanid prescribing information

Egaten (triclabendazole)

Triclabendazole is an antihelmintic agent indicated for the treatment of fascioliasis caused by Fasciola hepatica or Fasciola gigantica in patients aged 6 years or older. The mechanism by which triclabendazole exhibits its effect against Fasciola species is not fully elucidated. Studies in vitro and/or in infected animals suggest that triclabendazole and its active metabolites (sulfoxide and sulfone) are absorbed by the tegument of the immature and mature worms, leading to a decrease of the resting membrane potential and inhibition of tubulin function and protein and enzyme synthesis.

Prior to its approval in 2019, triclabendazole was available for many years via investigational protocols from the US Centers for Disease Control and Prevention. An open label, randomized trial conducted in Vietnam compared the efficacy of triclabendazole (two 10 mg/kg doses given 12 hours apart with food) with oral artesunate (4 mg/kg, given once daily for 10 days) (n=100). Patients (age range, 9-74 years) with acute symptomatic fascioliasis were randomized, 50 in each treatment group. At 3 months after treatment, 92% and 76% (difference 16%; 95% confidence interval, 1.7-30.8; P=.035) of patients in the triclabendazole and artesunate arms, respectively, reported no clinical symptoms. Six open-labeled studies showed the dose response at 20 mg/kg was superior to that of lower doses.

Egaten prescribing information

Dengvaxia (dengue vaccine)

Dengue vaccine was approved by the FDA for individuals aged 9-16 years with laboratory-confirmed previous dengue infection and living in endemic areas. It elicits dengue-specific immune responses against the 4 dengue virus serotypes (ie, serotypes 1, 2, 3, and 4). It is only approved for individuals previously infected by any dengue virus serotype or for whom this information is unknown. Those not previously infected are at increased risk for severe dengue disease when vaccinated and subsequently infected with dengue virus.

The approval was based on data from 2 placebo-controlled studies in patients (n>35,000) living in dengue-endemic areas. Patients were randomized 2:1 to receive either the vaccine or saline placebo and monitored for symptomatic virologically confirmed dengue (VCD) starting at day 0. Vaccine efficacy was assessed beginning 28 days after the third vaccination, for 12 months. The vaccine was approximately 76% effective in preventing symptomatic VCD disease among patients aged 9-16 years who were seropositive for dengue at baseline.

Dengvaxia prescribing information

Recarbrio (imipenem/cilastatin/relebactam)

Imipenem/cilastatin/relebactam contains previously approved imipenem/cilastatin and relebactam, a new beta-lactamase inhibitor. It is indicated for complicated urinary tract infections (cUTIs), including pyelonephritis, and complicated intra-abdominal infections (cIAIs) in adults with limited or no other treatment options.

Imipenem is a carbapenem that inhibits bacterial cell-wall synthesis by binding to penicillin-binding proteins, resulting in bacterial cell lysis. Cilastatin prevents renal metabolism of imipenem by competing with dehydropeptidase in the renal tubules to improve systemic exposure of imipenem. Relebactam has no intrinsic antibacterial activity. It protects imipenem from degradation by certain serine beta-lactamases such as sulfhydryl variable (SHV), temoneira (TEM), cefotaximase-Munich (CTX-M), E cloacae P99 (P99), Pseudomonas-derived cephalosporinase (PDC), and Klebsiella pneumoniae carbapenemase (KPC).

Efficacy of the antibiotic combination was supported in part by the findings of the efficacy and safety of imipenem-cilastatin for the treatment of cUTIs and cIAIs. Relebactam was assessed based on data from in vitro studies and animal models of infection. Safety was studied in 2 clinical trials, one each for cUTIs and cIAIs. The cUTI trial included 298 adult patients with 99 treated with the proposed dose. The cIAI trial included 347 patients with 117 treated with the proposed dose. Dosage modifications are necessary for patients who have renal impairment.

Recarbrio prescribing Information

Additional 2019 Infectious Disease approvals

Baxdela (delafloxacin) is indicated for treatment of community-acquired bacterial pneumonia.

Zerbaxa (ceftolozane/tazobactam) was approved for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.

Avycaz (ceftazidime/avibactam) was approved for complicated urinary tract infections, including pyelonephritis, in adults and children as young as 3 months.

Biktarvy (bictegravir/emtricitabine/tenofovir AF) was approved for children with HIV-1 infection who weigh at least 25 kg.

Tybost (cobicistat) is indicated to increase systemic exposure of atazanavir in combination with other antiretroviral agents for HIV-1–infected pediatric patients weighing at least 35 kg.

Dovato (dolutegravir/lamivudine) is the first 2-drug, fixed-dose complete regimen for treatment-naive adults with HIV-1 infection with no known substitutions associated with resistance to dolutegravir or lamivudine.

Sirturo (bedaquiline) was approved for multidrug-resistant pulmonary tuberculosis in children aged 12 years or older.

Sovaldi (sofosbuvir) is indicated for chronic hepatitis C virus infection as a component of a combination antiviral regimen in children aged 3 years or older.

Harvoni (ledipasvir/sofosbuvir) is indicated for hepatitis C virus infection as a component of a combination antiviral regimen in children aged 3 years or older.


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