Updates from FDA
New drugs
INEBILIZUMAB-CDON
(Uplizna—Viela Bio)
Drug class: CD19-directed cytolytic antibody
Indication: Treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-aquaporin-4 (AQP4) antibody positive
Recommended dosage: Administered as an I.V. infusion titrated to completion, approximately 90 minutes. The recommended initial dose is a 300-mg I.V. infusion followed 2 weeks later by a second 300-mg I.V. infusion. The recommended subsequent dose (starting 6 months from the first infusion) is a single 300-mg I.V. infusion every 6 months.
Common adverse effects: Urinary tract infection and arthralgia
Warnings and precautions: Infusion reactions, infections, immunoglobulin levels, fetal risk
Contraindications: Previous life-threatening reaction to infusion of the drug, active hepatitis B infection, active or untreated latent tuberculosis
New Indication
BUROSUMAB-TWZA
(Crysvita—Ultragenyx Pharmaceutical)
Drug class: Fibroblast growth factor 23 (FGF23) blocking antibody
Indication: Treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in patients aged 2 years and older
Recommended dosage: For pediatric patients, the starting dose is 0.4 mg/kg of body weight rounded to the nearest 10 mg every 2 weeks. Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every 2 weeks. For adult patients, the starting dose is 0.5 mg/kg every 4 weeks. Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every 2 weeks.
Common adverse effects: Tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache
Warnings and precautions: Hypersensitivity, hyperphosphatemia, risk of nephrocalcinosis, injection site reactions
Contraindications: Oral phosphate and/or active vitamin D analogs; when serum phosphorus is within or above the normal range for age; and in patients with severe renal impairment or end-stage renal disease.
CANAKINUMAB
(Ilaris—Novartis)
Drug class: Interleukin-1 beta-blocker
Indication: Active Still’s disease, including adult-onset Still’s disease
Recommended dosage: 4 mg/kg (with a maximum of 300 mg) for patients with a body weight greater than or equal to 7.5 kg. Administer by S.C. injection every 4 weeks.
Common adverse effects: Infections (nasopharyngitis and upper respiratory tract infections), abdominal pain, and injection-site reactions
Warnings and precautions: Interleukin-1 blockade may interfere with immune response to infections, so the drug has been associated with an increased risk and incidence of serious infections. Live vaccines should not be given concurrently.
Contraindications: Confirmed hypersensitivity to the active substance or any of the excipients
DOLUTEGRAVIR
(Tivicay, Tivicay PD—ViiV Healthcare)
Drug class: HIV-1 integrase strand transfer inhibitor (INSTI)
Indication: Treatment of HIV-1 infection in pediatric patients at least 4 weeks old and weighing at least 3 kg who have never been treated for HIV or who have been treated but not with an INSTI, in combination with other antiretroviral treatments
Recommended dosage: Dosing recommendations depend on patient’s body weight. Recommended dose is 5 mg once daily for patients 3 kg to less than 6 kg; 15 mg once daily for patients 6 kg to less than 10 kg; 20 mg once daily for patients 10 kg to less than 14 kg; 25 mg once daily for patients 14 kg to less than 20 kg; 30 mg once daily for patients 20 kg and greater
Common adverse effects: Insomnia, fatigue, and headache
Warnings and precautions: Hypersensitivity reactions, hepatotoxicity, embryo-fetal toxicity, immune reconstitution syndrome. Tivicay tablets and Tivicay PD tablets for oral suspension are not interchangeable.
Contraindications: Previous hypersensitivity reaction to dolutegravir and coadministration with dofetilide
FENFLURAMINE
(Fintepla—Zogenix)
Drug class: Anticonvulsant
Indication: Treatment of seizures associated with Dravet syndrome in patients aged 2 years and older
Recommended dosage: Administered orally and may be taken with or without food. The initial starting and maintenance dosage is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability.
Common adverse effects: Decreased appetite, somnolence, sedation, lethargy, diarrhea, constipation, abnormal echocardiogram, fatigue, malaise, asthenia, ataxia, balance disorder, gait disturbance, increased blood pressure, drooling, salivary hypersecretion, pyrexia, upper respiratory tract infection, vomiting, decreased weight, fall, and status epilepticus
Boxed warning: Valvular heart disease and pulmonary arterial hypertension
Warnings and precautions: Decreased appetite and decreased weight; somnolence, sedation, and lethargy; suicidal behavior and ideation; withdrawal of antiepileptic drugs; serotonin syndrome; increased blood pressure; and glaucoma
Drug interactions: Dose adjustments for patients taking stiripentol plus clobazam, and for those using strong CYP1A2 and CYP2B6 inducers.
Contraindications: Hypersensitivity to fenfluramine or any of the excipients, and concomitant use or within 14 days of administration of monoamine oxidase inhibitors because of an increased risk of serotonin syndrome
PEMBROLIZUMAB
(Keytruda—Merck)
Drug class: Programmed death receptor-1 (PD-1)–blocking antibody
Indication: First immunotherapy approved as a first-line treatment of patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer
Recommended dosage: 200 mg every 3 weeks or 400 mg every 6 weeks administered as an I.V. infusion over 30 minutes
Common adverse effects: Fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain
Warnings and precautions: Immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis, immune-mediated skin adverse reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, other immune-mediated adverse reactions, infusion-related reactions, embryo-fetal toxicity
FDA approves breast cancer at-home treatment
On June 29, 2020, FDA approved Phesgo (Genentech, Inc.) for treatment of adult patients with HER2-positive metastatic breast cancer and adult patients with early HER2-positive breast cancer. The drug, a combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf, is administered through S.C. injection. It is initially used in combination with chemotherapy but can continue to be administered at home by a qualified health professional.
“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of FDA’s Oncology Center of Excellence, and acting director of the Office of Oncologic Diseases in FDA’s Center for Drug Evaluation and Research.
The approval is part of FDA’s wider efforts to keep a strong focus on patients with cancer and other vulnerable populations during the COVID-19 pandemic.
Phesgo’s prescribing information includes a boxed warning for cardiomyopathy, embryo-fetal toxicity, and pulmonary toxicity. The drug’s most common side effects are alopecia, nausea, diarrhea, anemia, and asthenia. It can also worsen chemotherapy-induced neutropenia.
Patients who experience anaphylaxis or severe hypersensitivity reactions to Phesgo should discontinue the drug.
FDA permits marketing of digital therapeutic for ADHD in children
On June 15, 2020, FDA allowed marketing of EndeavorRx (Akili Interactive), the first game-based digital therapeutic device for use in children with ADHD. The device is prescription only and is indicated for pediatric patients aged 8 to 12 years with primarily inattentive or combined-type ADHD who have demonstrated an attention issue.
EndeavorRx is the first digital therapeutic granted marketing authorization by FDA for ADHD or for any type of condition. It is intended to be used as part of a therapeutic program that may include clinician-directed therapy, medication, and educational programs.
“The EndeavorRx device offers a non-drug option for improving symptoms associated with ADHD in children and is an important example of the growing field of digital therapy and digital therapeutics,” said Jeffrey Shuren, MD, JD, director of FDA’s Center for Devices and Radiological Health.
Data from multiple studies in more than 600 children informed the agency’s decision to grant the device marketing authorization. The most common adverse events associated with the device are frustration, headache, dizziness, emotional reaction, and aggression. No serious adverse events were reported.