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Pharmaceutical Approval Update July 2017
Manufacturer: Tesaro, Inc., Waltham, Massachusetts
Date of Approval: March 27, 2017
Indication: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
Drug Class: Antineoplastics, PARP inhibitors
Uniqueness of Drug: Niraparib is the third PARP inhibitor to receive approval from the Food and Drug Administration (FDA). However, unlike olaparib (Lynparza, AstraZeneca) and rucaparib (Rubraca, Clovis Oncology), the use of niraparib is not limited to women with a BRCA mutation, and it is approved for women whose cancer has recurred after receiving chemotherapy. Niraparib is the first PARP inhibitor that does not require BRCA mutation or other biomarker testing. Niraparib was evaluated by the FDA using fast-track, priority review, and breakthrough therapy designations. It was also granted an orphan drug designation.
Warnings and Precautions:
Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). MDS/AML, including cases with fatal outcomes, have been reported in patients who received niraparib. The duration of niraparib treatment in patients prior to developing MDS/AML ranged from less than one month to two years. All patients had received previous platinum-based chemotherapy, and some had also received other DNA-damaging agents and radiotherapy. Monitor patients for hematologic toxicity, and discontinue niraparib if MDS/AML is confirmed.
Bone marrow suppression. Hematologic adverse reactions (thrombocytopenia, anemia, and neutropenia) have been reported in patients treated with niraparib. Do not start niraparib until patients have recovered (to grade 1 or better) from hematologic toxicity caused by previous chemotherapy. Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter for clinically significant changes. If hematologic toxicities do not resolve within 28 days following interruption of treatment, discontinue niraparib and refer the patient to a hematologist for further investigations, including bone marrow analysis and cytogenetic blood samples.
Cardiovascular effects. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with niraparib. Manage with antihypertensive medications and adjust the niraparib dose if necessary.
Embryo-fetal toxicity. Niraparib can cause fetal harm. Advise women of reproductive potential of the risk to a fetus and to use effective contraception.
Dosage and Administration: The recommended dose of niraparib as monotherapy is 300 mg (three 100-mg capsules) taken orally once daily. Patients should take their dose at approximately the same time each day. Each capsule should be swallowed whole and may be taken with or without food. Administration of the dose at bedtime may be a potential method for managing nausea.
Patients should start treatment with niraparib no later than eight weeks after their most recent platinum-containing regimen. Continue niraparib treatment until disease progression or unacceptable toxicity. In the case of a missed dose, patients should take their next dose at its regularly scheduled time. If a patient vomits or misses a dose, an additional dose should not be taken.
Commentary: The FDA approval of niraparib was based on a randomized, placebo-controlled, phase 3 study that involved 553 patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers. Niraparib reduced the risk of progression or death by 74% compared with placebo for patients with germline BRCA-positive platinum-sensitive, recurrent ovarian cancer. Common adverse reactions experienced with niraparib (at an incidence of 10% or greater) included thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, and other events. (See full prescribing information for a detailed listing of adverse reactions.)
Sources: Tesaro, Inc., Zejula prescribing information
Manufacturer: Genentech, Inc., South San Francisco, California
Date of Approval: March 28, 2017
Indication: Ocrelizumab is a CD20-directed cytolytic antibody indicated for the treatment of patients with relapsing (RMS) or primary progressive (PPMS) forms of multiple sclerosis.
Drug Class: Monoclonal antibodies
Uniqueness of Drug: Ocrelizumab is the first drug approved by the Food and Drug Administration (FDA) for the treatment of PPMS. Ocrelizumab will be available as a first-line treatment and must be dispensed with the patient medication guide that describes the drug’s uses and risks. The FDA granted this application breakthrough therapy designation, fast-track designation, and priority review.
Warnings and Precautions:
Infusion reactions. Ocrelizumab can cause many different infusion reactions, including pruritus, rash, urticaria, erythema, and others. (See full prescribing information for a detailed listing.) The management recommendations for infusion reactions depend on the type and severity of the reaction. Ocrelizumab should be discontinued if a life-threatening or disabling infusion reaction occurs.
Infections. Delay ocrelizumab administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with ocrelizumab and after discontinuation until B-cell repletion.
Malignancies. An increased risk of malignancy may exist with ocrelizumab. In controlled trials, malignancies, including breast cancer, occurred more frequently in ocrelizumab-treated patients. Breast cancer occurred in six of the 781 women treated with ocrelizumab and none of the 668 women treated with interferon beta-1a (Rebif, EMD Serono, Inc.) or placebo. Patients should follow standard breast cancer screening guidelines.
Dosage and Administration: Hepatitis B virus screening is required before the first dose. Premedicate with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (e.g., diphenhydramine) prior to each infusion.
Ocrelizumab must be diluted following manufacturer instructions prior to administration. The initial starting dose is 300 mg via intravenous (IV) infusion, followed two weeks later by a second 300-mg IV infusion. Subsequent doses of 600 mg via IV infusion can then be administered every six months. Monitor patients closely during and for at least one hour after infusion.
Commentary: The efficacy of ocrelizumab for the treatment of RMS was shown in two clinical trials in which 1,656 participants were treated for 96 weeks. Both studies compared ocrelizumab with Rebif. The patients receiving ocrelizumab had fewer relapses and reduced worsening of disability compared with those who received Rebif. In a study of PPMS in 732 participants treated for at least 120 weeks, patients receiving ocrelizumab showed a longer time to the worsening of disability compared with placebo. The most common adverse events (at an incidence of 10% or greater) were upper and lower respiratory tract infections, infusion reactions, and skin infections.
Sources: Genentech, Inc., Ocrevus prescribing information
Manufacturer: Regeneron Pharmaceuticals, Inc., Tarrytown, New York
Date of Approval: March 28, 2017
Indication: Dupilumab is an interleukin-4 receptor alpha antagonist indicated for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD) (also known as eczema) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupilumab can be used with or without topical corticosteroids.
Drug Class: Interleukin inhibitors
Uniqueness of Drug: The Food and Drug Administration (FDA) approved dupilumab as a breakthrough treatment for extensive AD. It is a subcutaneous injection administered twice a month. AD treatments have generally been limited to topical medications, steroid creams, moisturizers, and ultraviolet light, plus antihistamines to relieve itching. While those treatments work fairly well for mild disease, they are less effective for the more severe (and more common) forms of AD. The FDA granted this application priority review and breakthrough therapy status.
Warnings and Precautions:
Hypersensitivity reactions. Hypersensitivity reactions, including generalized urticaria and serum sickness or serum sickness-like reactions, were reported in less than 1% of patients who received dupilumab in clinical trials. If a systemic hypersensitivity reaction occurs, discontinue dupilumab immediately and initiate appropriate therapy.
Conjunctivitis and keratitis. Conjunctivitis and keratitis occurred more frequently in patients who received dupilumab. Conjunctivitis was the most frequently reported eye disorder. Most patients with conjunctivitis recovered or were recovering during the treatment period. Advise patients to report new-onset or worsening eye symptoms to their health care provider.
Comorbid asthma. The safety and efficacy of dupilumab have not been established in the treatment of asthma. Advise patients with comorbid asthma not to adjust or stop their asthma treatments without consultation with their physicians.
Dosage and Administration: The recommended initial dose of dupilumab for adult patients is 600 mg, given as two 300-mg subcutaneous injections at different injection sites. Subsequent administrations of one 300-mg injection may be given every other week. Dupilumab is intended for use under the guidance of a health care provider. A patient may self-inject dupilumab after training in proper technique using the prefilled syringe. The injections should be given into the thigh or abdomen, except for the 2 inches around the navel. The upper arm can also be used if a caregiver administers the injection. Rotate the injection site with each injection. Do not inject dupilumab into skin that is tender, damaged, bruised, or scarred.
Dupilumab can be used with or without topical corticosteroids. Topical calcineurin inhibitors may be used, but should be reserved for problem areas only, such as the face, neck, and intertriginous and genital areas. If a dose is missed, instruct the patient to administer the injection within seven days from the missed dose and then resume the original schedule. If the missed dose is not administered within seven days, instruct the patient to wait until the next dose on the original schedule.
Commentary: The safety and efficacy of dupilumab were established in three placebo-controlled clinical trials with a total of 2,119 adults with moderate-to-severe AD not adequately controlled by topical medications. Overall, patients who received dupilumab achieved greater response, defined as clear or almost clear skin, and experienced a reduction in itch after 16 weeks of treatment. The most common adverse reactions (at an incidence of 1% or greater) were injection-site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infections, and dry eye.
Sources: Regeneron Pharmaceuticals, Inc., Dupixent prescribing information