Updates from FDA
New drugs
SACITUZUMAB GOVITECAN-HZIY
(Trodelvy—Immunomedics)
Drug class: Trop-2-directed antibody and topoisomerase inhibitor drug conjugate
Indication: To treat adult patients with metastatic triple-negative breast cancer who have received at least two prior therapies for metastatic disease
Recommended dosage: 10 mg/kg once weekly administered via I.V. infusion on days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity
Adverse effects: Nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, hair loss, constipation, decreased appetite, rash, abdominal pain
Boxed warning: Severe neutropenia and severe diarrhea may occur.
Other warnings and precautions: Hypersensitivity, nausea/vomiting, increased risk for neutropenia in patients with reduced uridine diphosphateglucuronosyl transferase 1A1 activity, embryo-fetal toxicity
CAPMATINIB
(Tabrecta—Novartis)
Drug class: Kinase inhibitor
Indication: First FDA-approved treatment for adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymalepithelial transition exon 14 skipping, as detected by a companion diagnostic, the FoundationOne CDx assay
Recommended dosage: 400 mg orally twice daily with or without food
Adverse effects: Leg swelling, nausea, fatigue, vomiting, shortness of breath, decreased appetite
Warnings and precautions: Interstitial lung disease or pneumonitis, hepatotoxicity, risk of photosensitivity, embryo-fetal toxicity; avoid concomitant use with strong and moderate CYP3A inducers.
PEMIGATINIB
(Pemazyre—Incyte)
Drug class: Kinase inhibitor
Indication: First treatment approved for adults with previously treated, advanced cholangiocarcinoma, a rare form of cancer that forms in bile ducts, in which tumors have a fusion or other rearrangement of the fibroblast growth factor receptor 2 gene, as detected by an FDA-approved test
Recommended dosage: 13.5 mg orally once daily for 14 consecutive days, followed by 7 days off therapy in 21-day cycles, until disease progression or unacceptable toxicity. Tablets are swallowed whole, with or without food.
Adverse effects: Hyperphosphatemia and hypophosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite,vomiting, joint pain, abdominal pain, back pain, dry skin
Warnings and precautions: Ocular toxicity (retinal pigment epithelial detachment), increases in phosphate levels, embryo-fetal toxicity
SELPERCATINIB
(Retevmo—Loxo Oncology)
Drug class: Kinase inhibitor
Indication: To treat adult patients with metastatic “rearranged during transfection” (RET) fusion-positive NSCLC; adult and pediatric patients ages 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy; and adult and pediatric patients ages 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)
Recommended dosage: In patients weighing less than 50 kg, 120 mg orally twice daily; in patients weighing 50 kg or greater, 160 mg orally twice daily. Dose should be reduced in patients with severe hepatic impairment.
Adverse effects: Increased AST/ALT, increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, constipation
Warnings and precautions: Hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, embryo-fetal toxicity. Nursing women should not breastfeed.
New indications
ENCORAFENIB
(Braftovi—Array BioPharma)
Drug class: Kinase inhibitor
Indication: In combination with cetuximab, to treat adult patients with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.
Recommended dosage: 300 mg orally once daily in combination with cetuximab, with or without food
Adverse effects: Fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, rash
Warnings and precautions: New primary malignancies, hemorrhage, uveitis, QT prolongation, embryo-fetal toxicity
DAPAGLIFLOZIN
(Farxiga—AstraZeneca)
Drug class: Sodium–glucose cotransporter 2 (SGLT2) inhibitor
Indication: First SGLT2 inhibitor to be approved to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with New York Heart Association’s functional Class II–IV heart failure with reduced ejection fraction
Recommended dosage: 10 mg once daily
Adverse effects: Female genital mycotic infections, nasopharyngitis, UTIs.
Warnings and precautions: Volume depletion, ketoacidosis in patients with diabetes, urosepsis and pyelonephritis, hypoglycemia, necrotizing fasciitis of the perineum (Fournier’s Gangrene) in patients with diabetes, genital mycotic infections
LUSPATERCEPT-AAMT
(Reblozyl—Celgene)
Drug class:Drug class: Erythroid maturation agent
Indication: Treatment of anemia failing an erythropoiesis-stimulating agent and requiring two or more red blood cell units over 8 weeks in adult patients with very low-risk to intermediate-risk myelodysplastic syndromes with ring sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis
Recommended starting dose: 1 mg/kg once every 3 weeks by S.C. injection; hemoglobin results should be reviewed prior to each administration.
Adverse effects: Fatigue, headache, musculoskeletal pain, arthralgia, dizziness/vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, hypersensitivity
Warnings and precautions: Thrombosis/thromboembolism, hypertension, embryo-fetal toxicity
FDA authorizes emergency use of remdesivir for patients with severe COVID-19 infection
On May 1, 2020, FDA issued an emergency use authorization (EUA) to Gilead for the investigational antiviral drug remdesivir to be distributed in the United States and administered intravenously by health care providers, as appropriate, to treat suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.
Patients with severe disease have low blood oxygen levels or need oxygen therapy or more intensive breathing support, such as a mechanical ventilator.
While there is limited information about remdesivir’s safety and effectiveness for treatment of COVID-19, the drug was shown in a clinical trial to shorten the time to recovery in some patients, according to FDA.
Issuance of an EUA is different from an FDA approval. In determining whether to issue an EUA, the agency evaluates the available evidence and carefully balances any known or potential risks of any unproven products with any known or potential benefits of making them available during the emergency.
On this basis, the agency determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the drug’s known and potential risks.
Possible adverse effects include increased levels of liver enzymes, which may be a sign of inflammation or damage to cells in the liver; and infusion-related reactions, which may include low blood pressure, nausea, vomiting, sweating, and shivering.
The EUA also requires that fact sheets providing important information about use of remdesivir to treat COVID-19, including dosing instructions, potential adverse effects, and drug interactions, be made available to health care providers and patients.
New quadrivalent meningococcal vaccine approved for ages 2 years and older
FDA has approved meningococcal (groups A, C, Y, W) conjugate vaccine under the trade name MenQuadfi (Sanofi) to prevent invasive meningococcal disease in persons aged 2 years and older. It is the first and only quadrivalent meningococcal vaccine in the United States to use tetanus toxoid as a protein carrier. The vaccine comes in a ready-to-use liquid formulation.
FDA approval was based on clinical data from five double-blind, randomized, multicenter Phase II and III trials involving nearly 5,000 persons aged 2 years and older. Additional data were presented at the 2019 European Society for Paediatric Infectious Diseases Annual Meeting and IDWeek 2019.
MenQuadfi demonstrated a high immune response and was well tolerated across all four serogroups for multiple ages, including in adolescents when the vaccine was coadministered with other routinely recommended vaccines. Its performance as a booster was also established.
Four of the trials evaluated MenQuadfi in meningococcal-naive persons; the other trial evaluated MenQuadfi in persons previously immunized with a quadrivalent meningococcal vaccine.
Against each of the four meningococcal serogroups (A, C, W, Y), the majority (55.4%–97.2%) of meningococcal-naive trial participants had a vaccine-induced immune response 30 days following vaccination with MenQuadfi. Among adolescents and adults previously vaccinated, 92.2% to 98.2% demonstrated an immune response against each serogroup.
Ongoing Phase III trials are investigating use of MenQuadfi in infants as young as 6 weeks to better address the worldwide needs for meningococcal disease prevention throughout life.
The most common adverse effects following a first dose of MenQuadfi included injection site pain, muscle ache, headache, and tiredness.
In adolescents and adults receiving a MenQuadfi booster, similar rates of these reactions were observed.
MenQuadfi is expected to be available to providers and pharmacies nationwide in 2021.