FDA Drug Approvals, Pediatrics — 2020 Midyear Review

August 14, 2020


Dojolvi (triheptanoin)

Triheptanoin is indicated as a source of calories and fatty acids for molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAODs) in adults and children. It is a medium-chain triglyceride consisting of 3 odd-chain 7-carbon-length fatty acids (heptanoate) that provide a source of calories and fatty acids to bypass the LC-FAOD enzyme deficiencies for energy production and replacement.

For this rare disease, a small double-blinded, randomized, controlled trial of 32 subjects with LC-FAODs (carnitine palmitoyltransferase-2, very long-chain acylCoA dehydrogenase, trifunctional protein, or long-chain 3-hydroxy acylCoA dehydrogenase deficiencies) were randomly assigned a diet containing 20% of their total daily energy from either triheptanoin or trioctanoin. At 4 months, patients in the triheptanoin group increased left ventricular (LV) ejection fraction by 7.4% (P=.046) while experiencing a 20% (P=.041) decrease in LV wall mass on their resting ECG. They also required a lower heart rate for the same amount of work during a moderate-intensity exercise stress test when compared with patients taking trioctanoin.

( J Inherit Metab Dis 2017 Nov;40(6):831-843)

Infectious Disease


Artesunate is an antimalarial artemisinin derivative. It is rapidly metabolized to the active metabolite, dihydroartemisinin (DHA). Artesunate and DHA, like other artemisinins, contain an endoperoxide bridge that is activated by heme iron that leads to oxidative stress, inhibition of protein and nucleic acid synthesis, ultrastructural changes, and decreased parasite growth and survival. Artesunate and DHA are active against the blood-stage asexual parasites and gametocytes of Plasmodium species, including the chloroquine-resistant strains.

Artesunate is administered intravenously and is indicated for adults and children for initial treatment of severe malaria. It should always be followed by a complete treatment course of an appropriate oral antimalarial regimen.

Artesunate IV was officially approved by the FDA in May 2020 (it was previously available from the CDC through an Investigative New Drug protocol). Approval was based the South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) and the African Quinine Artesunate Malaria Trial (AQUAMAT). These 2 studies examined a total of 6886 patients and included adults, children, and pregnant women. Artesunate IV reduced mortality by 34.7% (P=.0002) and 22.5% (P=.002) compared with quinine in the SEAQUMAT and AQUAMAT studies, respectively.

( Lancet 2005 Aug 27-Sep 2;366(9487):717-25

Lancet 2010 Nov 13;376(9753):1647-57)

Other pediatric infectious disease approvals

Sivextro (tedizolid) - Indicated for acute bacterial skin and skin structure infections in patients aged 12 years or older.

Tivicay PD (dolutegravir) - Indicated for HIV infection in children aged 4 weeks or older who weigh at least 3 kg.

Zosyn (piperacillin/tazobactam) - Indication for nosocomial pneumonia expanded to include children as young as 2 months.

Epclusa (sofosbuvir/velpatasvir) - Indicated for chronic hepatitis C virus infection in children aged 6 years or older or weighing at least 17 kg.

Sirturo (bedaquiline) - Indication for multidrug-resistant pulmonary tuberculosis expanded to include children aged 5 years or older.

Remdesivir - FDA granted an emergency use authorization for remdesivir to treat hospitalized patients with suspected or confirmed SARS CoV-2 infection and severe COVID-19 disease.


Retevmo (selpercatinib)

Selpercatinib is a kinase inhibitor of wild-type rearranged during transfection (RET) and multiple mutated RET isoforms, as well as vascular endothelial growth factor receptors (VEGFR1, VEGFR3). Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. Selpercatinib is indicated for metastatic RET fusion-positive non-small cell lung cancer (NSCLC) in adults. It is also indicated for advanced or metastatic RET-mutant medullary thyroid cancer (MTC) in adults and children aged 12 years or older who required systemic therapy.

In the open-label LIBRETTO-001 phase 1/2 clinical trial (n=144) for adults with NSCLC, the overall response rate was 64% in treatment-experienced patients (n=105) and 85% in treatment-naive patients (n=39). Results for patients with MTC (n=143) showed the overall response rate was 69% in cabozantinib/vandetanib treatment-experienced patients (n=55) and 73% in treatment-naive patients (n=88).

(Retevmo prescribing information)

Tazverik (tazemetostat)

Tazemetostat is an enhancer of zeste homolog 2 (EZH2) inhibitor. Uncontrolled EZH2 enzyme activity results in poorly regulated genes that control cancer cell proliferation. Tazemetostat is indicated for metastatic or locally advanced epithelioid sarcoma not eligible for complete resection in adults and adolescents aged 16 years or older. It is also indicated for adults with relapsed or refractory follicular lymphoma in patients whose tumors are positive for EZH2 mutation and who have received at least 2 prior systemic therapies, or those who have no satisfactory treatment options.

Approval for epithelioid sarcoma was based on a phase 2 trial (n=62). The overall response rate was 15%, with 1.6% of patients having a complete response and 13% having a partial response. Of the 9 patients who had a response, 6 (67%) patients had a response lasting 6 months or longer. Approval for follicular lymphoma was based on a phase 2 study. In the 53 patients treated with at least 2 prior systemic therapies, the overall response rate was 34% (4% complete response, 30% partial response). The median duration of response was 13 months.

(Tazverik prescribing information)

Other pediatric oncology approvals

Crysvita (burosumab) - Indicated for FGF23-related hypophosphatemia in tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors.

Mylotarg (gemtuzumab) - Indication for newly diagnosed CD33+ acute myeloid leukemia expanded to include pediatric patients aged 1 month or older.

Gardasil 9 (human papillomavirus vaccine nonavalent) - Indication now includes prevention of head and neck cancers.


Koselugo (selumetinib)

Selumetinib is an inhibitor of mitogen-activated protein kinases 1 and 2 (MEK1/2). MEK 1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Inhibition of ERK phosphorylation is thought to reduce neurofibroma numbers, volume, and proliferation. Selumetinib is indicated for neurofibromatosis type 1 (NF1) in pediatric patients aged 2 years or older who have symptomatic, inoperable plexiform neurofibroma.

FDA approval was based on results from the phase 2 SPRINT Stratum 1 trial, in which 50 patients with NF1 received selumetinib as twice-daily oral monotherapy. Of this group, 33 (66%) patients had a partial response of at least a 20% reduction in tumor volume.

( N Engl J Med 2020 Apr 9;381(15):1430-1442)

Other pediatric neurology approvals

Fintepla (fenfluramine) - Reintroduced to US market with new indication for seizures associated with Dravet syndrome in patients aged 2 years or older.

Cymbalta (duloxetine) - Indication for fibromyalgia now includes adolescents aged 13-17 years.

VESIcare LS (solifenacin) - New liquid formulation approved for neurogenic detrusor overactivity in children aged 2 years or older.


Dupixent (dupilumab) - Indicated for moderate-to-severe atopic dermatitis not adequately controlled with topical prescription therapies or when those therapies are not advisable in children aged 6 years or older.

Jublia (efinaconazole) - Indication for onychomycosis expanded to include children as young as 6 years.

Taltz (ixekizumab) - Indication for plaque psoriasis expanded to include children aged 6 years or older.

Eucrisa (crisaborole topical) - Indicated for mild-to-moderate atopic dermatitis in infants and children aged 3 months or older.


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