The fixed-dose combination of nivolumab/relatlimab is indicated for treatment of adults and pediatric patients aged 12 years and older with unresectable or metastatic melanoma. Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody, and relatlimab is a lymphocyte activation gene-3 (LAG-3) blocking antibody. The combination results in increased T-cell activation compared to the activity of either antibody alone.
Approval in March 2022 was based on the RELATIVITY-047 phase 2/3 global trial, which found a median progression-free survival (PFS) of 10.1 months in 355 patients randomly assigned to the combination therapy, compared to 4.6 months in 359 patients who received nivolumab alone (HR, 0.75; P=0.0055). N Engl J Med. 2022 Jan 6;386(1):24-34
Other pediatric hematology-oncology approvals
Vidaza (azacitidine) – New indication approved for juvenile myelomonocytic leukemia.
Xalkori (crizotinib) – New indication for adults and children aged 1 year and older with unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumors (IMT).
Mekinist (trametinib) in combination with Tafinlar (dabrafenib) – Granted accelerated approval for adults and children aged 6 years and older with unresectable/metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options.
Ganaxolone is a GABAA receptor–positive modulator. It binds specifically to GABAA receptors to enhance their inhibitory effects. It is indicated for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2 years and older. CDD, a rare developmental epileptic encephalopathy, is largely a disease of pediatric and young adult patients.
Approval was based on the phase 3 MARIGOLD trial. Patients treated with ganaxolone (n = 49) showed a median 30.7% reduction in 28-day major motor seizure frequency, compared to a 6.9% reduction for those receiving placebo (n = 51) (P=0.0036). In the open-label extension study, patients treated with ganaxolone for at least 12 months (n = 48) experienced a median 49.6% reduction in major motor seizure frequency. Prescribing Information
Other pediatric neurology approvals
Hyftor (sirolimus topical) – New dosage form indicated for treatment of facial angiofibroma associated with tuberous sclerosis in patients aged 6 years and older.
Fintepla (fenfluramine) – New indication for seizures associated with Lennox-Gastaut syndrome (previously approved for seizures associated with Dravet syndrome) in patients aged 2 years and older.
Diacomit (stiripentol) – Indication for seizures associated with Dravet syndrome expanded to include children as young as 6 months (previously approved for aged 2 years and older).
Evrysdi (risdiplam) – Indication for spinal muscular atrophy expanded to include children younger than 2 months.
Opzelura (ruxolitinib topical)
Ruxolitinib topical cream received approval in July 2022 for the treatment of adults and adolescents aged 12 years and older with nonsegmental vitiligo. Approval was based on data from two phase 3 trials (TRuE-V1 and TRuE-V2) that evaluated the safety and efficacy of ruxolitinib cream compared to vehicle in more than 600 people.
Topical ruxolitinib resulted in significant improvements in vitiligo area scoring index (VASI), which represent improvements in facial and total body repigmentation, at week 24 (primary analysis) compared to vehicle and in an open-label extension at week 52. Results at week 24, which were consistent across both studies, showed approximately 30% of patients treated with topical ruxolitinib achieved at least 75% improvement from baseline in facial repigmentation (F-VASI75), the primary endpoint, compared to approximately 8% and 13% of patients treated with vehicle in TRuE-V1 and TRuE-V2, respectively. At week 52, approximately 50% of ruxolitinib-treated patients achieved F-VASI75.
Additionally, at week 24, more than 15% of patients treated with topical ruxolitinib achieved at least 90% improvement from baseline in F-VASI (F-VASI90), compared to approximately 2% of patients treated with vehicle. At week 52, the percentage of ruxolitinib-treated patients who achieved F-VASI90 doubled to approximately 30%. Medscape Medical News
Alpelisib is the first drug approved for patients aged 2 years and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy. Klippel-Trenaunay-Weber syndrome is part of this spectrum of diseases. FDA approval of alpelisib was supported by real-world evidence from the open-label EPIK-P1 trial. A retrospective chart review showed patients treated with alpelisib had reduced target lesion volume and improvement in PROS-related symptoms and manifestations. After 24 weeks, 27% of patients (10/37) achieved a confirmed response to treatment, defined as 20% or greater reduction in the sum of PROS target lesion volume. Also, 23 of 31 patients (74%) showed some reduction in target lesion. Prescribing Information
Other pediatric dermatology approvals
Rinvoq (upadacitinib) – Indicated for refractory moderate-to-severe atopic dermatitis in patients aged 12 years and older.
Dupixent (dupilumab) – Indication for atopic dermatitis expanded to include children as young as 6 months (previously approved for patients aged 6 years and older).
Stelara (ustekinumab) – Indication for psoriatic arthritis expanded to include children aged 6 years and older.
Zerbaxa (ceftolozane/tazobactam) – Indication for eosinophilic esophagitis in adults and adolescents aged 12 years and older who weigh at least 40 kg.
Descovy (emtricitabine/tenofovir AF) – Indication for treatment of HIV infection in combination with antiretroviral agents other than protease inhibitors expanded to include children who weigh at least 14 kg (previously approved for children weighing at least 35 kg).
Triumeq, Triumeq PD (abacavir/dolutegravir/lamivudine) – Indication for HIV treatment expanded to include children weighing at least 10 kg; additionally, a tablet for suspension approved for precise dosing in those weighing <25 kg.
Cabenuva (cabotegravir/rilpivirine) – Indication for HIV treatment expanded to include adolescents aged 12 years and older who weigh at least 35 kg; additionally, lead-in oral therapy is now optional.
Solosec (secnidazole) – Indication for bacterial vaginosis expanded to include females aged 12 years and older. Indication for trichomoniasis expanded to include males and females aged 12 years and older.
Vaxneuvance (pneumococcal vaccine, 15-valent) – 4-dose immunization series approved for children at least 6 weeks of age to prevent Pneumococcal pneumoniae infections (previously approved in adults).
Priorix (measles, mumps, and rubella [MMR] vaccine live) – New brand approved for active immunization for prevention of MMR in individuals aged 1 year and older.
COVID-19 Approvals & Emergency Use Authorizations
mRNA COVID-19 vaccines
CDC interim recommendations for individuals aged 6 months and older includes regimens for those who are immunosuppressed.
CDC interim recommendations also state that an 8-week interval may be optimal for some people aged 12 years and older, especially for males aged 12-39 years because of the small risk of myocarditis associated with mRNA COVID-19 vaccines
EUA extended to include children aged 6 months through 4 years (previously authorized for 5 years and older).
Full approval granted for adolescents aged 12 years and older.
Emergency use granted to prevent COVID-19 in children aged 6 months through 17 years.
Veklury (remdesivir) – Full approval was granted for adults and children to allow outpatient infusions for treatment of COVID-19. The indication includes adults and children aged 28 days and older (weighing at least 3 kg) who require hospitalization or who are not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Two monoclonal antibodies are available in the United States. Bebtelovimab is used for postexposure prophylaxis in patients at high risk for progression to severe COVID-19 (or when other COVID-19 treatment options are not available or clinically appropriate). Tixagevimab plus cilgavimab is used for preexposure prophylaxis in individuals who are moderately to severely immunocompromised because of a medical condition or treatments and would otherwise not mount a sufficient immune response to a vaccine (also for those with confirmed severe allergy to the vaccines).
Other monoclonal antibodies (ie, sotrovimab, bamlanivimab/etesevimab, casirivimab/imdevimab) previously used for postexposure prevention are no longer being distributed because of decreased efficacy against omicron variants.
Bebtelovimab – EUA issued for treatment (ie, postexposure prophylaxis) of mild-to-moderate COVID-19 in adults and pediatric patients aged 12 years and older who weigh 40 kg or more at high risk for progressing to severe disease.
Evusheld (tixagevimab and cilgavimab) – EUA revised for preexposure prophylaxis of COVID-19 with an increased dose of tixagevimab 300 mg IM and cilgavimab 300 mg IM administered as separate, consecutive IM injections. Patients who have already received the previously authorized dose (150 mg of tixagevimab and 150 mg of cilgavimab) should receive an additional dose of 150 mg of tixagevimab and 150 mg of cilgavimab as soon as possible to raise their monoclonal antibody levels to those expected for patients receiving the higher dose.
Imcivree (setmelanotide) – Indication for chronic weight management in patients aged 6 years and older with obesity caused by certain genetic disorders expanded to include Bardet-Biedl syndrome.
Qsymia (phentermine/topiramate) – Indication for chronic weight management expanded to include adolescents aged 12 years and older with an initial BMI in the 95th percentile or greater for age and sex.
Ryaltris (olopatadine/mometasone intranasal) – New fixed-dose combination indicated for seasonal allergic rhinitis in patients aged 12 years and older.
Acuvue Theravision with Ketotifen (ketotifen, drug-eluting contact lens) – Daily disposable contact lenses indicated for the prevention of ocular itch caused by allergic conjunctivitis and to provide vision correction in patients aged 11 years and older who do not have red eyes, who are suitable for contact lens wear, and who do not have more than 1.00 D of astigmatism.
Nephroscan (technetium Tc 99m succimer) – New technetium diagnostic imaging agent to aid in scintigraphic evaluation of renal parenchymal disorders in adult and pediatric patients.
Xelstrym (dextroamphetamine transdermal) – New transdermal patch indicated for treatment of attention deficit hyperactivity disorder (ADHD) in adults and children aged 6 years and older.
Zulresso (brexanolone) – Indication for postpartum depression expanded to include adolescents aged 15 years and older.
Dupixent (dupilumab) – New indication approved for eosinophilic esophagitis in adults and adolescents aged 12 years and older who weigh at least 40 kg.
CellCept (mycophenolate mofetil) – Indication for prophylaxis of organ rejection in patients receiving allogeneic heart and liver transplants expanded to include children aged 3 months and older.
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Cite this: FDA Drug Approvals, Pediatrics — 2022 Midyear Review - Medscape - Aug 24, 2022.