New Drug Approvals and Extended Indications for Infants, Children, and Adolescents

Marcia L. Buck, PharmD, FCCP, FPPAG


Pediatr Pharm. 2015;21(11) 

In This Article

New Drug Product Approvals

Adapalene and Benzoyl Peroxide

Epiduo Forte®, a new product containing adapalene 0.3%, a retinoid, and benzoyl peroxide 2.5% was approved on July 16, 2015 for the treatment of moderate to severe acne in adults and children 12 years of age and older.[1] The efficacy of the new product was demonstrated in a phase 3 multicenter randomized, double-blind trial comparing it to the gel vehicle without the two active ingredients and a combination product containing adapalene 0.1% and benzoyl peroxide 2.5%.[2] Patients in the adapalene and benzoyl peroxide groups had significantly greater reductions in skin lesion count at 12 weeks, with a mean absolute reduction of 68.7% versus 39.2% in the controls. Many patients experienced improvement after the first week. Fifty percent of the patients receiving active treatment rated themselves as having a marked improvement, compared to only 11% of the controls. Adverse effects were mild, consisting of skin irritation in 4% of patients and eczema, dermatitis, or a burning sensation in 1%. Adapalene and benzoyl peroxide gel may offer an effective alternative to the long-term use of antibiotics for the treatment of moderate to severe acne.

Amphetamine Extended-release Suspension

A once-daily amphetamine oral suspension (Dyanavel™ XR) was approved by the FDA on October 19, 2015 for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older.[3] The product includes both immediate-release and extended-release amphetamine. The extended-release component is coated with an aqueous polymer which slowly releases the drug over time, providing up to 13 hours of symptom control. The safety and efficacy of the product was established in a phase 3 randomized, placebo-controlled trial in 108 children with ADHD.[4] Following a 5-week open-label dose optimization period, patients were randomized to treatment (2.5–10 mg) or placebo for a 1-week period. At the end of the week, scores on the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Combined rating scale were compared to baseline. The change in scores after treatment demonstrated a statistically significant improvement throughout the day compared to placebo (assessed at 1, 2, 6, 8, 10, 12, and 13 hours post-dose), with a mean change of -8.8 (SE 1.14) in the treated patients and 6.0 (SE 1.19) in the controls. Dyanavel™ XR contains 2.5 mg amphetamine base/mL, equivalent to 4 mg of mixed amphetamine salt, in a bubble-gum flavored suspension. Tris Pharma anticipates having the product available in early 2016.

Asfotase Alfa

On October 23, 2015, the FDA approved the use of asfotase alfa (Strensiq™), a tissue nonspecific alkaline phosphatase enzyme replacement therapy for patients with perinatal, infantile, or juvenile-onset hypophosphatasia (HPP).[5] Affecting approximately one in 100,000 newborns, HPP is a progressive metabolic disease resulting in muscle weakness and defective bone mineralization. Asfotase alfa replaces tissue-nonspecific alkaline phosphatase, improving formation of normal bone. The efficacy and safety of the drug were established in four open-label studies.[6,7] In patients with perinatal or infantile-onset HPP, asfotase alfa improved both overall survival and ventilator-free survival. Ninety-seven percent of patients were alive at one year of age, compared to an anticipated 42% based on historical controls. In studies of patients with juvenile-onset HPP, there were significant improvements in growth and bone mineralization.

Asfotase alfa is administered by injection three or six times per week. The most commonly reported adverse effects in patients enrolled in the open-label studies were injection site reactions, hypersensitivity reactions, lipodystrophy at injection sites, and ectopic calcifications in the eyes or kidneys.[5–7] The drug was granted both Breakthrough Therapy and Orphan Drug designations by the FDA.

Cysteamine Bitartrate Delayed-release Capsules

A delayed-release form of cysteamine bitartrate (Procysbi®) was approved by the FDA on August 14, 2015 for management of nephropathic cystinosis in adults and children 6 years of age and older.[8,9] Cysteamine bitartrate immediate-release tablets (Cystagon®) were approved by the FDA in 1994. The slower release of drug from the Procysbi capsule allows for twice-daily dosing rather than the every 6-hour dosing required for Cystagon®. The approval of the delayed-release product was based on a randomized cross-over study comparing it to the immediate-release tablets in 43 children and adults. The two products were equally effective in controlling cysteine levels. Cysteamine bitartrate delayed-release was given an Orphan Drug designation by the FDA.

Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide

On November 5, 2015, the FDA approved a fixed-dose combination tablet of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (Genvoya®) for the management of HIV-1 infection in adults and children 12 years of age and older who weigh at least 35 kg.[10,11] This once-daily product may be used in either treatment naïve patients or those who have already been receiving treatment. The combination contains a prodrug of tenofovir that produces higher concentrations within cells with lower serum concentrations, providing effective antiviral activity with fewer adverse effects on renal function and bone mineral density.[12]


The FDA approved mepolizumab (Nucala®) for the management of severe asthma in patients 12 years of age and older on November 4, 2015.[13] Mepolizumab is a humanized monoclonal antibody to interleukin-5. It is given by subcutaneous injection every 4 weeks by a health care professional to monitor for hypersensitivity reactions.[14] Mepolizumab was evaluated in three premarketing randomized, double-blind placebo-controlled trials. In the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) study, 576 adolescents and adults were randomized to receive either a 75 mg IV dose or 100 mg subcutaneous dose of mepolizumab or placebo. All patients remained on their current asthma medications. The rate of exacerbations was reduced by 47% in the IV mepolizumab group and 53% in the subcutaneous group as compared to the placebo group (p < 0.001 for both comparisons). Emergency room visits or hospitalizations were reduced by 32% and 61% in the two treatment groups, respectively.[15] In the combined results of premarketing studies, a reduction in steroid use of 50% or more was documented in 54% of the treated patients versus 33% of the controls. Twenty-three percent of treated patients achieved a 90–100% reduction in steroid use, compared to only 11% of the controls. The most common adverse effects reported with mepolizumab include headache (19% of patients), injection site reactions (8%), and back pain (5%). Symptoms associated with hypersensitivity reactions have been reported in 1–2% of patients.[14]

Uridine Triacetate

Uridine triacetate was approved on September 4, 2015 for the treatment of patients with hereditary orotic aciduria (HOA).[16] Patients with HOA are unable to synthesize uridine, an essential component of RNA, and are prone to anemia, neutropenia, developmental delays, failure to thrive, and urinary tract obstructions caused by orotic acid crystals in the urinary tract.[17] Uridine triacetate is available in oral granules that can be mixed with food, milk, or infant formula. It is administered once daily. The safety and efficacy of uridine triacetate were evaluated in a 6-week open-label trial in four patients with HOA (3–19 years of age). This study was followed by a 6-month extension phase. At 6-week and 6-month evaluations, treatment resulted in stable hematologic parameters. No adverse effects have been reported with treatment up to 9 months. Uridine triacetate was granted Orphan Drug status by the FDA, as well as a rare pediatric disease priority review voucher.