Pediatric Updates From the Food and Drug Administration

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


Pediatr Pharm. 2019;25(4) 

In This Article

New Drug and Drug Product Approvals


The first monoclonal antibody to treat children and adults with x-linked hypophosphatemia (XLH), burosumab (Crysvita®) was approved in 2018. XLH, a rare inherited form of rickets, affects approximately 15,000 patients in the United States and causes bowed legs and short stature, as well as bone, joint, and dental pain. The approval of burosumab was based on the results of four clinical trials conducted in 148 adults and 65 children. In an open-label study of burosumab in 52 children 5–12 years of age, mean serum phosphorus levels increased from 2.4 + 0.40 mg/dL at baseline to 3.4 + 0.45 mg/dL at week 64.


In 2018, the first proprietary cannabinoid product (Epidiolex®) was approved as an adjunctive therapy for the treatment of seizures in adults and children 2 years of age and older with Lennox Gastaut syndrome (LGS) or Dravet syndrome occurred in 2018. Cannabidiol was the first drug to be approved specifically for the treatment of patients with Dravet syndrome. Data supporting approval came from three phase 3 trials enrolling more than 1,000 pediatric and adult patients.

Clobazam Oral Film

Clobazam has been an important component in the management of LGS and other refractory seizure disorders since its approval in 2011. A new oral film (Sympazan™) was recently approved to provide an alternative for patients unable to swallow the tablets or large volumes of the oral suspension. The berry-flavored film is available in 5 mg, 10 mg, and 20 mg strengths.

Digital Inhaler

Teva Pharmaceutical Industries introduced their new albuterol digital inhaler (ProAir® Digihaler™) at the end of 2018. This is the first digital inhaler; it includes built-in sensors that connect to a mobile app to provide data on inhaler use to the patient, family, and potentially to healthcare providers. In addition to measuring when the inhaler is used, it evaluates inspiratory flow. The ProAir® Digihaler™ is approved by the FDA for use in patients 4 years of age and older.


The enzyme replacement therapy, elapegademase-lvlr (Revcovi™), has been approved for children and adults with adenosine deaminase severe combined immune deficiency (ADA-SCID). It is a PEGylated recombinant form of adenosine deaminase that supplements the patient's endogenous levels without the need to rely on animal sources.


The FDA approved the first drug specifically indicated for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) in 2018. It is indicated for use in patients with progressive, refractory, or recurrent disease. The efficacy of emapalumab-lzsg (Gamifant®) was demonstrated in a study of 27 children with HLH who failed to respond to or were unable to tolerate traditional HLH therapy. Sixty-three percent of the patients responded to treatment, and 70% were able to proceed to stem cell transplant.

Epoetin Alfa-epbx

The first biosimilar for epoetin (Retacrit™) was approved last year. As a biosimilar, epoetin alfa-epbx has no clinically significant differences in potency, purity, or safety compared to the original biological product. Biosimilars, however, are not considered interchangeable products. The availability of biosimilars is intended to provide competition, potentially reducing patient costs and increasing accessibility. Epoetin alfa-epbx carries the same indications as the original product and is approved for the treatment of anemia in children with cancer receiving chemotherapy or those with chronic kidney disease.

Hexavalent Vaccine

In December, the FDA approved the first product to contain six vaccines in the childhood immunization series (Vaxelis®). It contains diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus, Haemophilus b conjugate (meningococcal protein conjugate), and hepatitis B (recombinant) vaccines. The hexavalent vaccine was developed through a joint venture between Sanofi and Merck. It is currently in production and is expected to be available in 2020 when a sustainable supply can be maintained.


The first monoclonal antibody for the treatment of types I and II hereditary angioedema (HAE), lanadelumab-flyo (Takhzyro™) was approved by the FDA for patients 12 years of age and older. Lanadelumab, a plasma kallikrein inhibitor, was approved based on the results of a multicenter randomized, double-blind placebo-controlled trial in 125 adolescents and adults.[1] The percentage of patients without an HAE attack for the entire 26-week treatment period was 44%, 31%, and 39% in the patients given 300 mg lanadelumab every 2 weeks, 300 mg every 4 weeks, and 150 mg given every 4 weeks respectively, compared to 2% of placebo patients. An open-label continuation study demonstrated a sustained benefit.

Methylphenidate Delayed-release, Extended-release

The new delayed-release, extended-release methylphenidate product, Jornay PM™, was approved by the FDA for the treatment of ADHD in children 6 years of age and older last year. This unique product uses the Delexis® drug delivery platform to provide a dosage formulation that could be given at night to delay absorption, resulting in effective serum methylphenidate concentrations at breakfast and continuing throughout the day.


River blindness, caused by the parasitic worm Onchocerca volvulus, is a devastating tropical illness endemic in lower income countries. Moxidectin was developed though a collaboration of Medicines Development for Global Health and the World Health Organization Special Program for Research and Training in Tropical Diseases for the treatment of river blindness. In a phase 3 study, moxidectin produced significantly greater suppression of microfilariae in skin than ivermectin. It is currently approved for patients 8 years of age and older.


Several acne products were approved in the past year, including sarecycline (Seysara™), a first-in-class tetracycline-derivative. It provides a new option for oral treatment of non-nodular moderate-to-severe acne vulgaris in patients 9 years of age and older. Sarecycline is taken once daily and typically produces improvement within 3 weeks after starting treatment. Improvement in Investigator Global Assessment scores of acne severity in the two premarketing studies were 21% and 22.6% in the treatment groups, compared to 10.5% and 15.3% in the placebo groups, respectively.


A second drug for the treatment of refractory seizures in patients with Dravet syndrome, stiripentol (Diacomit®) was approved in December 2018. Stiripentol is a direct allosteric modulator of GABAA receptors and offers a unique mechanism of action that benefits both patients with and without sodium channel α-1 subunit gene (SCN1A) mutations. In phase 3 trials, over 60% of patients experienced a 50% or greater reduction in seizure frequency.


Tafenoquine has been approved by the FDA for the prevention of relapse of Plasmodium vivax malaria in patients 16 years of age and older. Administered as a single dose, it is designed to provide a clinical cure, preventing future relapse. Tafenoquine was developed through a partnership between GSK and the Medicines for Malaria Venture. Development began in 2008; it was given Breakthrough Therapy status in 2013.

Tezacaftor/Ivacaftor and Ivacaftor

The FDA approved the combination tezacaftor/ivacaftor and ivacaftor (Symdeko®) in February 2018 for the treatment cystic fibrosis in patients 12 years of age and older with two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or patients with one mutation that is responsive to tezacaftor/ivacaftor. This is the third product from Vertex Pharmaceuticals for patients with CF. Efficacy and safety for this combination was established in the EVOLVE and EXPAND trials.[3,4] These two randomized, double-blind, placebo-controlled, phase 3, crossover trials enrolled more than 750 patients. In the EXTEND continuation study, the benefit in lung function seen in the EVOLVE and EXTEND studies was sustained for up to 48 weeks.

Tretinoin Lotion

A new lotion formulation of tretinoin (Altreno™ lotion) was approved for the treatment of moderate-to-severe acne vulgaris to children ages 9 years and older. Approval of this product was based on the results of two multicenter, randomized, double-blind, 12-week trials conducted in 1,640 adolescents and adults, as well as an open-label pharmacokinetic study.[5] Mean absolute reduction in inflammatory lesions was significantly greater in the treatment groups; 13.1 and 13.9 in the patients using tretinoin lotion, compared to 10.6 and 10.7 in the vehicle-only control groups.