News for Pediatric Healthcare Providers From the Food and Drug Administration

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS


Pediatr Pharm. 2018;24(4) 

In This Article

New Drug and Drug Product Approvals


Avelumab (Bavencio®), an anti-PD-L1 IgG1 monoclonal antibody, has been approved for the treatment of metastatic Merkel cell carcinoma in adults and children more than 12 years of age. Approval was based on the JAVELIN Merkel 200 trial, a multicenter open-label, non-comparator study in 88 adults showing an overall response rate of 33%, with a complete response in 11% and a partial response in 22%.[1]


An interleukin-5 receptor monoclonal antibody, benralizumab (Fasenra™) has been approved for the treatment of severe eosinophilic asthma in adults and pediatric patients 12 years of age and older.[2] By binding at the IL-5 receptor on the surface of eosinophils and basophils, it produces antibody-dependent cell elimination within 24 hours of administration. The 30 mg dose is administered subcutaneously once every 4 weeks for the first three doses, and then once every 8 weeks thereafter. Three phase 3 studies supported the drug's approval, demonstrating up to a 51% reduction in asthma exacerbation rates compared to placebo, with significant improvement in forced expiratory volume in 1 second (FEV1), and a 75% reduction in daily oral corticosteroid use.


In August 2017, the FDA announced the approval of benznidazole, the first medication for the treatment of Chagas disease, a parasitic infection caused by Trypanosoma cruzi.[3] Chronic T. cruzi infection may result in cardiac and gastrointestinal disease. Although more common in South America, Chagas disease affects approximately 200,000 people in the United States. The safety and efficacy of the drug was established in two phase 3 placebo-controlled trials in children 6–12 years of age. The percentage of children that became antibody negative was 60% in the benznidazole group compared to 14% in the controls. In the second study, the results were 55% and 5% for the two groups, respectively. The most common adverse effects were headache, abdominal pain, nausea, vomiting, rash, and hives. Serous dermatologic and nervous system reactions, as well as bone marrow suppression have also been reported.

Cerliponase Alfa

Cerliponase alfa (Brineura™) is a recombinant form of human tripeptidyl peptidase (TPP1) developed for the management of TPP1 deficiency, also known as neuronal ceroid lipofuscinosis type 2 (CLN2), in children 3 years of age and older. A dose of 300 mg is infused into the CSF via an implanted reservoir and catheter every other week. The approval was supported by the results of an open-label dose-escalation study over 96 weeks.[4] Twenty-four children from 3 to 8 years of age were enrolled. Of the 22 evaluated at week 96, 21 (95%) had no decline in the motor domain of the CLN2 clinical rating scale.


Approval for deflazacort (Emflaza®), an oxazoline derivative of prednisolone, in the treatment of Duchenne muscular dystrophy (DMD) was based on a 52-week phase 3 randomized, double-blind, placebo-controlled multicenter study.[5] Patients were randomized to receive deflazacort at a dose of either 0.9 mg/kg/day or 1.2 mg/kg/day, prednisone 0.75 mg/kg/day, or placebo for 12 weeks; after that point, patients in the placebo group were randomized to one of the active treatment groups. All treatment groups demonstrated significant improvement in muscle strength compared to placebo. Patients in the prednisone group had significantly more weight gain. Subsequent studies have confirmed deflazacort's more favorable adverse effect profile.[6] It is approved for use in patients 5 years of age and older with DMD.


In November 2017, the FDA approved a lower dose epinephrine auto-injector (AUVI-Q®) for the emergency management of anaphylaxis or other severe hypersensitivity reactions in infants and toddlers.[7] The new dosage strength, 0.1 mg, is designed for use in patients 7.5 to 15 kg, extending the range of patients covered by the current 0.15 mg and 0.3 mg devices. As with the other strengths, the 0.1 mg device should be held firmly against the thigh, through clothing if necessary. At the same meeting, the FDA approved a change in the labeling of all the AUVI-Q® devices shortening the time it must be held in place from 5 to 2 seconds after activation. Each auto-injector provides a single dose, with both oral and visual cues for use. The kit comes with two auto-injectors and a trainer.

L-glutamine Oral Powder

L-glutamine (Endari™), was approved in 2017 for the treatment of sickle cell disease in adults and children 5 years of age and older.[8,9] The approval was supported by a phase 3 randomized trial of 230 patients 5–58 years old with sickle cell disease who had two or more pain crises within the previous year. Patients were randomized to L-glutamine or placebo for the 48-week trial. The treatment group experienced fewer hospital visits for sickle cell pain crises requiring opioids or ketorolac compared to the controls (median 3 versus 4), fewer hospitalizations for sickle cell pain (median 2 versus 3), and fewer days in the hospital (median 6.5 days versus 11 days). Patients who received L-glutamine also had fewer episodes of acute chest syndrome (8.6% versus 23.1%).

Ozenoxacin 1% Cream

This new topical quinolone is approved for the treatment of impetigo in adults and children 2 months of age and older. Ozenoxacin (Xepi™) was approved based on the results of two phase 3 multicenter randomized, double-blind placebo-controlled studies. One of the studies has been published, showing a clinical success rate of 34.8% in the treatment group compared to 19.2% in the controls (p = 0.003), with a microbiological success rates of 79.2% and 56.6% at 6–7 days in the two groups, respectively.[10]


Tisagenlecleucel (Kymriah™) is used for CD19-directed genetically modified autologous T cell immunotherapy.[11] The patient's T cells are modified by a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing cells. Tisagenlecleucel is approved for children and adults less than 25 years of age with refractory B-cell precursor acute lymphoblastic leukemia. Approval was based on the results of a global phase 2 single-cohort study of 75 patients which demonstrated an overall survival rate of 90% (95% CI 81, 95) at 6 months and 76% (63, 86) at 12 months. Continued assessment of the study patients has shown the presence of tisagenlecleucel in the blood up to 20 months after a dose. Cytokine release syndrome occurred in 77% of patients, with 40% having transient neurologic events.

Voretigene Neparvovec-rzyl

Approval for voretigene neparvovec-rzyl (Luxturna™), gene replacement therapy for retinal pigment epithelial-65 mutation-associated retinal dystrophy, was based on data from a single phase 3 clinical trial.[12] After 1 year of treatment, comparison of the patients in the treatment group and controls using change in mean bilateral multi-luminance mobility testing (MLMT) scores showed a difference of 1.6 (95% CI 0.72, 2.41, p = 0.001). Change in full-field light sensitivity threshold and mobility test scores also showed significant improvement with treatment.