FDA Drug Approvals, Pediatrics — 2021 Midyear Review

August 20, 2021

Infectious Disease

Tembexa (brincidofovir)

Brincidofovir is a prodrug of cidofovir. Brincidofovir effectively penetrates cells via its lipid conjugate, releasing the nucleotide analog cidofovir, which then acts to inhibit viral replication. Cidofovir diphosphate selectively inhibits orthopoxvirus DNA polymerase–mediated viral DNA synthesis by incorporation of cidofovir into the growing viral DNA chain. This results in reductions in the rate of viral DNA synthesis. It is indicated for treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.

The drug gained approval under the FDA's animal rule. Approval was based on efficacy data in 2 lethal orthopoxvirus animal models of human smallpox disease, the rabbit pox model (New Zealand white rabbits infected with rabbit pox virus) and the mouse pox model (BALB/c mice infected with ectromelia virus). In the pivotal studies in each model, brincidofovir resulted in statistically significant survival benefit versus placebo following delayed treatment after animals were infected with a lethal viral dose. Tembexa prescribing information

Other pediatric infectious disease approvals

Natroba (spinosad) - New indication approved for scabies in adults and children aged 4 years and older.

Rapivab (peramivir) - Indication for acute uncomplicated influenza expanded to include children as young as 6 months.

Vaxchora (cholera vaccine) - Use for immunization against Vibrio cholerae serogroup 01 expanded to include children aged 2 years and older.

Infectious disease emergency use authorizations (EUAs)


Sotrovimab was granted an EUA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients aged 12 years or older who weigh at least 40 kg with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death.

The phase 3 trial COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) demonstrated sotrovimab significantly reduced the risk of hospitalization or death by 79% at day 29 among 1057 high-risk outpatients (P <.001). Day 29 analysis from COMET-ICE clinical trial

Etesevimab (plus bamlanivimab)

Etesevimab was issued an EUA for use in combination with bamlanivimab for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years and older weighing at least 40 kg. Treatment is dependent on positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing in patients who are at high risk for progressing to severe COVID-19 and/or hospitalization.

NOTE: Owing to the increase in variants of concern (VOCs) in the United States, monoclonal antibodies that have gained an EUA have been tested to evaluate activity against VOCs. As of March 24, 2021, US distribution ceased for bamlanivimab alone. On June 25, 2021, US distribution ceased for bamlanivimab plus etesevimab as the P.1/Gamma and B.1.351/Beta variants (first identified in Brazil and South Africa) exceeded 11% of cases throughout the United States. Consider use of casirivimab plus imdevimab or sotrovimab in outpatients who qualify for monoclonal antibodies.

In this arm of the phase 3 BLAZE-1 trial, the change in log viral load from baseline at day 11 was -3.72 for bamlanivimab 700 mg, -4.08 for bamlanivimab 2800 mg, -3.49 for bamlanivimab 7000 mg, -4.37 for combination treatment, and -3.80 for placebo. Among nonhospitalized patients with mild-to-moderate COVID-19 illness, treatment with bamlanivimab plus etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; however, no significant difference in viral load reduction was observed for bamlanivimab monotherapy. No difference in hospitalization rate was observed between bamlanivimab monotherapy or with the combination. Based on an analysis of available data, the authorized dosage regimen of the combination is bamlanivimab 700 mg plus etesevimab 1400 mg administered together as a single intravenous infusion. This regimen is expected to have similar clinical effects as the 2800-mg dosages evaluated in the study. JAMA. 2021;325(7):632-644

BNT-162b2 (COVID-19 vaccine, mRNA-Pfizer) - EUA for prevention of SARS-CoV-2 infection expanded to include adolescents aged 12 years and older.


Evkeeza (evinacumab)

Evinacumab is a recombinant human monoclonal antibody that binds to and inhibits angiopoietin–like 3 (ANGPTL3). ANGPTL3 inhibits lipoprotein lipase and endothelial lipase, thereby reducing lipid metabolism. Evinacumab inhibits ANGPTL3 and results in increased lipid metabolism, leading to decreased low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Evinacumab is indicated as an adjunct to other LDL-C–lowering therapies for homozygous familial hypercholesterolemia in adults and adolescents aged 12 years and older.

Approval was based on the phase 3 ELIPSE trial (n = 65). The study found that patients undergoing stable lipid-lowering treatment in whom an intravenous infusion of evinacumab was administered every 4 weeks achieved, by week 24, a 47.1% relative reduction in their LDL-C level, compared to a 1.9% increase in patients given placebo (P <.001). N Engl J Med. 2020;383:711-720

Other pediatric cardiology approvals

Arcalyst (rilonacept) - Interleukin-1 inhibitor for treatment of recurrent pericarditis and to reduce the risk of future recurrence in adults and children aged 12 years and older.

Pradaxa (dabigatran) - First oral anticoagulant approved for children to treat and prevent the recurrence of venous thromboembolic events.

Diovan (valsartan) - Indication for pediatric hypertension expanded to include children as young as 1 year.


Azstarys (serdexmethylphenidate/dexmethylphenidate)

Serdexmethylphenidate/dexmethylphenidate is a fixed-dose combination of the prodrug of dexmethylphenidate, serdexmethylphenidate, and immediate-release dexmethylphenidate. This combination provides extended drug levels. It is indicated for attention deficit hyperactivity disorder in adults and children aged 6 years and older. Efficacy was assessed by Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)–combined scores, compared to baseline and at 0.5, 1, 2, 4, 8, 10, 12, and 13 hours post dose. Results showed statistically significant improvement of SKAMP-combined scores compared to placebo. Azstarys prescribing information

Qelbree (viloxazine)

Viloxazine is indicated for treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years. The mechanism of action by which viloxazine affects ADHD is unclear; however, it may be by selectively inhibiting norepinephrine reuptake. Approval was based on 3 phase-3 placebo-controlled trials that included over 1000 participants. Patients taking viloxazine had statistically significant improvement in ADHD rating scale 5 and Clinical Global Impressions I scores. compared to placebo. Qelbree prescribing information

Other pediatric psychiatry approvals

Kloxxado (naloxone intranasal) - New formulation that delivers 8 mg per actuation, compared with older products that deliver 2 mg or 4 mg per actuation.

Evekeo ODT (amphetamine) - Indication for attention deficit hyperactivity disorder expanded to include children as young as 3 years (previously approved for children aged 6-17 years).


Rylaze (asparaginase Erwinia chrysanthemi recombinant)

Asparaginase Erwinia chrysanthemi recombinant is indicated as part of a chemotherapeutic regimen for acute lymphoblastic leukemia or lymphoblastic lymphoma in adults and children aged 1 month or older who have developed hypersensitivity or silent inactivation to Escherichia coli–derived asparaginase.

Ryplazim (plasminogen)

Plasminogen is the first therapy approved for plasminogen deficiency type 1 (hypoplasminogenemia). It is a plasma-derived human plasminogen that temporarily increases plasminogen blood levels. Activated plasminogen, plasmin, is a fundamental component of the fibrinolytic system, blood clot lysis, and extravasated fibrin clearance.

Other pediatric hematology-oncology approvals

Vyxeos (cytarabine/daunorubicin liposomal) - Indication for newly diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes expanded to include children aged 1 year and older.

Lymphoseek (technetium Tc 99m tilmanocept) - Indication for lymphatic mapping expanded to include children aged 1 year and older with solid tumors for which this procedure is a component of intraoperative management.

Ferriprox (deferiprone) - Indication for transfusional iron overload expanded to include children aged 3 years and older with sickle cell anemia or other anemias.


Amondys 45 (casimersen)

Casimersen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. PMO binds to exon 45 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Casimersen is indicated for Duchenne muscular dystrophy in patients with a confirmed mutation amenable to exon 45 skipping.

The ESSENCE trial—a placebo-controlled confirmatory trial to support the casimersen approval—is ongoing and expected to conclude in 2024. In the study, patients who received casimersen showed a significantly greater increase in dystrophin protein levels from baseline to week 48 of treatment, compared with those who received placebo. Study of SRP-4045 and SRP-4053 in DMD Patients (ESSENCE)

Nulibry (fosdenopterin)

Fosdenopterin is indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency type A (MoCD-A), a rare disease. Fosdenopterin provides an exogenous source of cyclic pyranopterin monophosphate (cPMP). MoCD-A is caused by a mutation in the molybdenum cofactor synthesis 1 gene (MOCS1), which causes a deficiency in molybdenum cofactor production. The exogenous intermediate substrate cPMP provided by the drug is subsequently converted to molybdenum cofactor, which is required for the activation of essential enzymes (eg, sulfite oxidase) to reduce the levels of neurotoxic sulfites. Decreased sulfite oxidase activity is thought to cause the severe and rapidly progressive CNS damage observed in patients with MoCD-A.

Other pediatric neurology approvals

Fabrazyme (agalsidase) - Indication for Fabry disease expanded to include children aged 2 years and older (previously approved for those aged 8 years and older).

Carbaglu (carglumic acid) - Approval granted for adjunctive therapy to standard of care for acute hyperammonemia due to propionic acidemia or methylmalonic acidemia in adults and children.


Humira (adalimumab) - Indication for ulcerative colitis expanded to include children aged 5 years and older.

Epclusa (sofosbuvir/velpatasvir) - Indication for chronic hepatitis C virus infection expanded to include children as young as 3 years.

Mavyret (glecaprevir/pibrentasvir) - Indication expanded to include children aged 3 years and older with chronic hepatitis C virus infection.

Pain Management

Exparel (bupivacaine liposomal) - New indication for postsurgical local analgesia expanded to include children aged 6 years and older.

Zipsor (diclofenac) - Indication for acute mild-to-moderate pain now includes adolescents.

Additional Pediatric Approvals

Nextstellis (estetrol/drospirenone)

Estetrol/drospirenone is indicated for use by females of reproductive potential to prevent pregnancy. The combination is the first to contain estetrol (E4), a synthetic analog of native estrogen that is present during pregnancy. It is selective for nuclear estrogen receptor (ER)–alpha and ER-beta. Treatment results in the decrease of follicle-stimulating hormone and luteinizing hormone, ultimately leading to ovulation suppression.

Zegalogue (dasiglucagon)

Dasiglucagon is a ready-to-use, stable glucagon analog indicated for severe hypoglycemia in pediatric and adult patients with diabetes. It is a glucagon receptor agonist that increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver.

Ragwitek (ragweed allergen extract) - Indication for immunotherapy for short ragweed pollen–induced allergic rhinitis expanded to include children as young as 5 years.

Children's Astepro Allergy (azelastine) - The 0.15% nasal spray is now available as an over-the-counter treatment for seasonal/perennial rhinitis in children aged 6 years and older.

Myrbetriq (mirabegron) - FDA approval gained for neurogenic detrusor overactivity in children aged 3 years and older.

Botox (onabotulinumtoxinA) - New indication approved for neurogenic detrusor overactivity in children aged 5 years and older who have an inadequate response to or are intolerant of anticholinergic medications.

Nplate (romiplostim) - New indication for treatment of adults and pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation.

Cosentyx (secukinumab) - Indication expanded for moderate-to-severe plaque psoriasis to include children aged 6 years and older who are candidates for systemic therapy or phototherapy.


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