2015: The Year in Oncology Drugs

WITH THE START OF THE NEW YEAR, we continue with a look back at the specialty pharmaceuticals featured prominently, in 2015, in the FDA’s new drug approval and expanded indications list. The second, of this 2-part installment, reviews approvals related to oncology drugs, as well as late-breaking FDA actions in other therapeutic categories.

Please consult the respective product-prescribing monographs for complete information, including dosing regimens.

LEUKEMIAS AND LYMPHOMAS

Imbruvica (ibrutinib, Pharmacyclics & Janssen Biotech, Inc) received an expanded indication on January 29, 2015, for the treatment of patients with Waldenström’s macroglobulinemia (WM), a rare form of cancer that begins in the body’s immune system. Imbruvica received a breakthrough therapy designation for this indication.

The drug is a Bruton’s Tyrosine Kinase inhibitor, which was initially approved, in November 2013, for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and in patients with CLL who carry a deletion in chromosome 17, which is typically associated with a poor response to standard treatment for CLL.

Imbruvica is dosed at 560 mg (four 140-mg capsules) taken orally once daily for MCL. The recommended dose for CLL and WM is 420 mg (three 140-mg capsules) taken orally once daily.^1,2

Bendeka (bendamustine hydrochloride, Teva Pharmaceuticals USA, Inc) was approved on December 7, 2015, for the treatment of patients with CLL, and patients with indolent B-cell non-Hodgkin lymphoma (NHL) who progressed, during or within 6 months of treatment, with rituximab or a rituximab-containing regimen. Efficacy of Bendeka in CLL relative to first-line therapies, other than chlorambucil, has not been established.

Bendeka was granted orphan drug designations for both CLL and indolent B-cell NHL. Bendeka is an alkylating, cytotoxic drug that is available in a 100-mg/4-ml (25-mg/ml) multi-dose vial for IV use. For CLL, the recommended dosage of Bendeka is 100 mg/m2 infused intravenously over 10 minutes on days 1 and 2 of a 28-day cycle, for up to 6 cycles.

For NHL, the recommended dosage is 120 mg/m2 infused IV over 10 minutes on days 1 and 2 of a 21-day cycle, up to 8 cycles. Treatment with Bendeka should be delayed in patients with grade 4 hematologic toxicity or clinically significant ≥ grade 2 nonhematologic toxicity.^3,4

MYELOMA

Revlimid (lenalidomide, Celgene Corp) received an expanded indication on February 18, 2015, for combination use with dexamethasone for patients with newly diagnosed multiple myeloma. Revlimid plus dexamethasone was originally approved in June 2006 for use in multiple myeloma patients who received at least 1 prior therapy.

The thalidomide analogue is also indicated for patients with MCL whose disease relapsed or progressed after 2 prior therapies (1 of which included bortezomib), and for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q abnormality, with or without additional cytogenetic abnormalities.

Due to the embryo-fetal-risk associated with Revlimid, it is only available through the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program. Prescribers and pharmacies must be certified with the Revlimid REMS program in order to prescribe and dispense to patients authorized to receive Revlimid, and comply with the requirements.

Revlimid is available in 2.5-mg, 5-mg, 10-mg, 15-mg, 20-mg, and 25-mg capsules. The recommended dosage of Revlimid is dependent upon the indication and usage. Revlimid should be taken orally at about the same time each day, either with or without food, and capsules should be swallowed whole.^5,6

Farydak (panobinostat, Novartis Pharmaceuticals) was approved on February 23, 2015, for the treatment of patients with multiple myeloma who received at least 2 prior treatments, including bortezomib, and an immunomodulatory agent. Farydak, a histone deacetylase inhibitor, was granted accelerated approval based on progression-free survival.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Farydak is available in 10-mg, 15-mg, and 20-mg capsules. The recommended dosage of Farydak is 20 mg orally on days 1, 3, 5, 8, 10, and 12 of each 21-day cycle, for 8 cycles.

Treatment may be continued for an additional 8 cycles in patients demonstrating a clinical benefit, unless there is unresolved, severe, or medically significant toxicity while on treatment.^7,8

Kyprolis (carfilzomib, Onyx Pharmaceuticals) received an expanded indication by the FDA on July 24, 2015, for relapsed multiple myeloma in combination with Revlimid and dexamethasone in patients who received 1 to 3 prior lines of therapy. The proteasome inhibitor (PI) is available as a 60-mg lyophilized powder in a single-dose vial for reconstitution.

For the combination regimen, Kyprolis is administered intravenously as a 10-minute infusion on 2 consecutive days each week for 3 weeks, followed by a 12-day rest period. Each 28-day period is considered 1 treatment cycle. Kyprolis is administered at a starting dose of 20 mg/m2/day in cycle 1 on days 1 and 2. If tolerated, the dose should be escalated to a target dose of 27 mg/m2/day on day 8 of cycle 1.^9,10

Darzalex (daratumumab, Janssen Biotech, Inc) was approved by the FDA on November 16, 2015, for the treatment of patients with multiple myeloma who received at least 3 prior treatments, including a PI and an immunomodulatory agent, or patients who are double refractory to a PI and an immunomodulatory agent.

This indication is approved under the accelerated approval based on the response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The human anti-CD38 monoclonal antibody is available in a 100-mg/5-ml and 400-mg/20-ml single-dose vial for administration as an IV infusion.

Darzalex should be only administered as an IV infusion after dilution by a health care professional, with immediate access to emergency equipment and appropriate medical support to manage infusion reactions if they occur. The recommended dose of Darzalex is 16-mg/kg IV administered weekly during weeks 1 to 8, then every 2 weeks during weeks 9 to 24, and then every 4 weeks from week 25 onward, until disease progression.^11,12

Ninlaro (ixazomib, Takeda Pharmaceutical Company Ltd) was approved on November 20, 2015, in combination with Revlimid and dexamethasone, for patients with multiple myeloma who have had at least 1 prior therapy. Ninlaro, the first oral PI approved by the FDA, was granted priority review and orphan drug designation. The treatment is available in 4-mg, 3-mg and 2.3-mg capsules.

The recommended starting dose is 4-mg orally on days 1, 8, and 15 of a 28-day cycle. The recommended starting dose of Revlimid, in this combination is 25-mg administered daily on days 1 through 21 of a 28-day treatment cycle. For dexamethasone, it is 40-mg administered on days 1, 8, 15, and 22 of a 28-day treatment cycle. Ninlaro should be taken at least 1 hour before or at least 2 hours after food.^13,14

Empliciti (elotuzumab, Bristol-Myers Squibb) was approved by the FDA on November 30, 2015, in combination with Revlimid and dexamethasone for patients with multiple myeloma who have received 1 to 3 prior therapies. The SLAMF7-directed immunostimulatory antibody was previously granted breakthrough therapy designation by the FDA.

Empliciti is available for IV injection in 300-mg or 400-mg lyophilized powder in a single-dose vial for reconstitution with sterile water for injection. The recommended dose of Empliciti is 10-mg/kg administered intravenously every week for cycles 1 and 2 (28 days per cycle), and then every 2 weeks for cycles 3 and beyond, along with the recommended dosing of Revlimid and low-dose dexamethasone as outlined in the prescribing information. Treatment with Empliciti should be continued until disease progression or unacceptable toxicity occurs.^15,16

SKIN CANCER

Odomzo (sonidegib, Novartis Pharmaceuticals) was approved by the FDA on July 24, 2015, for the treatment of adult patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or for patients who are not candidates for surgery or radiation therapy. The hedgehog pathway inhibitor is available in a 200-mg oral capsule.

The recommended dose is 200 mg taken orally, once daily, on an empty stomach at least 1 hour before or 2 hours after a meal. Since Odomzo can cause embryo-fetal death or severe birth defects, female patients are advised to use effective contraception during treatment and for at least 20 months after the last dose.

Male patients should also use condoms during treatment and for at least 8 months after the last dose to avoid potential drug exposure in female partners of reproductive potential. All patients are advised not to donate blood during treatment and for at least 20 months after the last dose.^17,18

Imlygic (talimogene laherparepvec, Amgen Inc) was approved on October 27, 2015, for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Imlygic has not been shown to improve overall survival or have an effect on visceral metastases. Imlygic is the first FDA-approved, genetically modified, live oncolytic herpes viral therapy.

It is available in single-use vials of 1 ml each, in 2 dosage strengths: 106 (1 million) plaque-forming units (PFU) per mL, for initial dose only, and 108 (100 million) PFU per mL for all subsequent doses. The treatment course consists of a series of injections of up to 4 mL into the melanoma lesions.

After the initial injection, a second dose is administered 3 weeks later, followed by additional doses every 2 weeks for at least 6 months, unless other treatment is required, or until there are no remaining injectable lesions to treat.

Health care providers, who are immunocompromised or pregnant, should not prepare or administer Imlygic and should not come into direct contact with the Imlygic injection sites, dressings, or body fluids of treated patients.^19,20

Yervoy (ipilimumab, Bristol Myers Squibb) received an expanded indication on October 28, 2015, as an adjuvant treatment for patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy. The human cytotoxic T-lymphocyte antigen blocking antibody was originally approved in March 2011 for the treatment of unresectable or metastatic melanoma.

Yervoy is available in dosage strengths of 50 mg/10 ml (5 mg/ml) and 200 mg/40 ml (5 mg/ml) in single-use vials that must be diluted with either 0.9% NaCl, USP or 5% dextrose injection, USP, prior to administration. The recommended dose for adjuvant treatment of melanoma is 10 mg/kg administered intravenously over 90 minutes every 3 weeks for 4 doses, followed by 10 mg/kg every 12 weeks for up to 3 years.^21,22

Cotellic (cobimetinib, Genentech) was approved on November 10, 2015, for use in combination with Zelboraf (vemurafenib) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. Cotellic is not indicated for patients with wild-type BRAF melanoma.

Cotellic was evaluated under the FDA Priority Review Program and also received orphan drug designation. The kinase inhibitor is available in a 20-mg tablet. It is important to confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of therapy.

The recommended dose is 60 mg orally once daily, with or without food, for the first 21 days, followed by a 7-day rest period for a 28-day cycle, until disease progression or unacceptable toxicity occurs.^23,24

LUNG CANCER

Opdivo (nivolumab, Bristol-Myers Squibb) received an expanded indication on March 4, 2015, for treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. On September 30, 2015, Opdivo received an additional approval for use in combination with Yervoy (ipilmumab) for patients with BRAF V600 wild-type melanoma.

On October 9, 2015, Opdivo received an expanded approval for patients with metastatic NSCLC whose disease progressed during or after platinum-based chemotherapy. Furthermore, on November 23, 2015, Opdivo was approved for a new indication in patients with metastatic renal cell carcinoma who received prior anti-angiogenic therapy.

The programmed death receptor-1 (PD-1) blocking antibody was initially approved in December 2014. It is available as a 40-mg/4-ml and 100-mg/10-ml solution for injection in a single-use vial. Opdivo should be diluted with either 0.9% NaCl injection, USP, or 5% dextrose injection, USP, in order to obtain a final concentration ranging from 1 mg/ml to 10 mg/ml, and then administered as an IV infusion over 60 minutes.^25-29

Iressa (gefitinib, AstraZeneca) was approved on July 13, 2015, for the first-line treatment of patients with metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test. The safety and efficacy of Iressa have not been established in patients whose tumors have EGFR mutations, other than exon 19 deletions or exon 21 (L858R) substitution mutations.

Iressa initially received accelerated approval in 2003, for patients with advanced NSCLC after progression on platinum doublet chemotherapy and docetaxel, but was voluntarily withdrawn from the market after subsequent confirmatory trials failed to verify clinical benefit. The current approval is for a different patient population (EGFR mutation-positive, previously untreated) than the 2003 approval.

The oral, EGFR tyrosine kinase inhibitor (TKI) was granted orphan drug designation by the FDA in August 2014, for EGFR mutation positive NSCLC. Iressa is available in a 250-mg tablet, and the recommended dosage is 250 mg orally once daily, with or without food.^30,31

Keytruda (pembrolizumab, Merck & Co, Inc) received expanded indication on October 2, 2015, for the treatment of patients with NSCLC whose disease has progressed after other treatments and with tumors that express the PD-L1 protein. Keytruda is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, designed to detect PD-L1 expression in non-small cell lung tumors.

The FDA granted Keytruda breakthrough therapy designation for this indication. Furthermore, on December 18, 2015, Keytruda received another expanded indication as a first-line treatment for patients with unresectable or metastatic melanoma. Keytruda was initially approved in September 2014 as an anti-PD-1 therapy for patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab), and if the patient is BRAF V600 mutation-positive, with a BRAF inhibitor.

Keytruda is available in a 50-mg lyophilized powder single-use vial for reconstitution and in a 100-mg/4-ml (25-mg/ml) solution in a single-use vial. The recommended dose is 2 mg/kg as an IV infusion over 30 minutes every 3 weeks. Keytruda should be diluted prior to IV infusion.^32-34

Tagrisso (osimertinib, AstraZeneca Pharmaceuticals) was approved on November 13, 2015, for the treatment of patients with metastatic EGFR T790M mutation positive NSCLC as detected by an FDA approved test, who have progressed on or after EGFR TKI therapy. This indication is approved under the accelerated approval process based on tumor response rate and duration of response.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Tagrisso is a kinase inhibitor available in 80-mg and 40-mg tablets. Before treatment with Tagrisso is initiated, the presence of the T790M mutation should be confirmed. The recommended dosage of Tagrisso is 80 mg orally once daily, with or without food.^35,36

Portrazza (necitumumab, Eli Lily and Co) was approved on November 24, 2015, in combination with gemcitabine and cisplatin, for patients with metastatic squamous NSCLC who have not previously received medication specifically, for advanced lung cancer. Portrazza is not indicated for non-squamous NSCLC. The EGFR antagonist is available in an 800-mg/50-ml (16-mg/ml) solution in a single-use vial for IV injection.

The recommended dose is 800 mg (absolute dose) as an IV infusion over 60 minutes on days 1 and 8 of each 3-week cycle. Prior to administration, the required volume is to be diluted only with 0.9% NaCl injection, USP, in an IV infusion container to a final volume of 250 ml.^37,38

Alecensa (alectinib, Genentech, Inc) was approved on December 11, 2015, for patients with anaplastic lymphoma kinase positive, metastatic NSCLC who progressed on, or are intolerant to, crizotinib. This indication was granted accelerated approval based on tumor response rate and duration of response.

The FDA also granted Alecensa breakthrough therapy designation, priority review status, and orphan drug designation. Continued approval for the above indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The oral anaplastic lymphoma kinase inhibitor is available in a 150-mg capsule. The recommended dosage is 600 mg (four 150-mg capsules) orally twice daily with food.^39,40

OTHER ONCOLOGY AND ONCOLOGY SUPPORT

Ibrance (palbociclib, Pfizer) was approved on February 3, 2015, as a combination treatment with Femara (letrozole), in postmenopausal women with ER-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for metastatic disease. The kinase inhibitor was approved under the FDA’s accelerated approval program.

Ibrance is available in a capsule formulation containing 125 mg, 100 mg, or 75 mg. Ibrance capsules are to be taken orally with food in combination with letrozole. The recommended dose is 125 mg once daily for 21 days, followed by 7 days off treatment, in combination with letrozole 2.5 mg once daily continuously throughout the 28-day cycle. Dosing interruption and/or dose reductions are recommended based on individual safety and tolerability.^41,42

Lenvima (lenvatinib, Eisai Co, Ltd) was approved on February 13, 2015, for locally recurrent or metastatic, progressive radioactive iodine-refractory differentiated thyroid cancer. The kinase inhibitor is available in a 4-mg and 10-mg capsule, with a recommended dosage of 24 mg orally once daily. In patients with severe renal or hepatic impairment, the dose should be reduced to 14 mg once daily. Treatment with Lenvima should be continued until disease progression or unacceptable toxicity associated with the medication.^43,44

Zarxio (filgrastim-sndz, Sandoz), a leukocyte growth factor, was approved on March 6, 2015, as the first biosimilar product in the United States. Zarxio is a biosimilar to Amgen Inc’s Neupogen (filgrastim), which was originally approved in 1991.

Zarxio is approved for the same indications as Neupogen: in patients receiving myelosuppressive chemotherapy, patients with acute myeloid leukemia receiving induction or consolidation chemotherapy, patients undergoing bone marrow transplantation, patients undergoing autologous peripheral blood progenitor cell collection and therapy, and patients with severe chronic neutropenia. Zarxio is available in a 300-mcg/0.5-ml and 480-mcg/0.8-ml single—use, prefilled syringe with BD UltraSafe Passive Needle Guard.^45,46

Unituxin (dinutuximab, United Therapeutics Corporation) was approved on March 10, 2015, for pediatric patients with high-risk neuroblastoma who achieved at least a partial response to prior first-line multi-agent, multimodality therapy. Unituxin is a GD2-binding monoclonal antibody used in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2, and 13-cis-retinoic acid.

Unituxin is available in a 17.5-mg/5-ml (3.5-mg/ml) single-use vial for injection. The recommended dosage of Unituxin is 17.5 mg/m2 per day as a diluted IV infusion over 10 to 20 hours, for 4 consecutive days for up to 5 cycles. Unituxin comes with a boxed warning indicating the risk of infusion reactions and severe neuropathy requiring treatment with intravenous narcotics.^47,48

Cyramza (ramucirumab, Eli Lilly and Company) received an expanded indication on April 24, 2015, for use in combination with Folfiri (irinotecan, folinic acid, and 5-fluorouracil) in second-line treatment of metastatic colorectal cancer with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Cyramza was originally approved in 2014 as a single agent to treat patients with advanced stomach cancer or gastro-esophageal junction (GEJ) adenocarcinoma with disease progression, on or after prior fluoropyrimidine or platinum-containing chemotherapy. Cyramza has also been approved to treat patients with advanced gastric or GEJ adenocarcinoma in combination with paclitaxel and for metastatic NSCL with disease progression, on or after platinum-based chemotherapy, in combination with docetaxel.

Cyramza is available in 100-mg/10-ml or 500-mg/50-ml single-dose vials of solution. The recommended dose of Cyramza for patients with colorectal cancer is 8 mg/kg every 2 weeks administered by IV infusion over 60 minutes prior to Folfiri administration. Cyramza should be continued until disease progression or unacceptable toxicity.^49-51

Varubi (rolapitant, Tesaro Inc) was approved on September 2, 2015, for use in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Varubi is a substance P/neurokinin 1 receptor antagonist. Varubi is available in a 90-mg tablet with a recommended dosage of 2 tablets (180 mg) given approximately 1 to 2 hours prior to the start of chemotherapy.

Varubi should not be taken more than once every 14 days, and it can be taken with or without food. Varubi should be given in combination with dexamethasone and a 5-HT3 receptor antagonist. No dosage adjustment for dexamethasone is required.^52,53

Lonsurf (tipiracil hydrochloride and trifluridine, Taiho Oncology) was approved on September 22, 2015, for patients with metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and an anti-EGFR therapy for RAS wild-type colorectal cancer.

Lonsurf is a combination of the nucleoside metabolic inhibitor trifluridine and the thymidine phosphorylase inhibitor tipiracil. Lonsurf is available as a tablet in 2 dosage strengths: 15-mg trifluridine/6.14-mg tipiracil and 20-mg trifluridine/8.19-mg tipiracil.

The recommended dose is 35 mg/m2 (based on the trifluridine component) orally, twice daily, on days 1 through 5 and days 8 through 12 of each 28-day cycle. Lonsurf should be taken within 1 hour after completion of morning and evening meals.^54,55

Onivyde (irinotecan liposome injection, Merrimack Pharmaceuticals, Inc) was approved on October 22, 2015, in combination with fluorouracil and leucovorin, for metastatic adenocarcinoma of the pancreas, after disease progression following gemcitabine-based therapy. Onivyde is not indicated as a single agent for metastatic adenocarcinoma of the pancreas.

The drug was granted priority review and orphan drug designations by the FDA. The topoisomerase inhibitor is available in a single-dose vial containing 43-mg irinotecan-free base at a concentration of 4.3 mg/ml. Onivyde must not be substituted for other drugs containing irinotecan HCl and should be administered prior to leucovorin and fluorouracil.

The recommended dose is a 70-mg/m2 IV infusion over 90 minutes every 2 weeks. The recommended starting dose in patients known to be homozygous for UGT1A1*28 allele is 50 mg/m2 every 2 weeks administered by IV infusion over 90 minutes. The dose may be increased to 70 mg/m2 as tolerated in subsequent cycles.^56,57

Yondelis (trabectedin, Janssen Biotech, Inc), an alkylating drug, was approved on October 23, 2015, for patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Yondelis is available as a 1-mg sterile lyophilized powder in a single-dose vial for IV use.

The recommended dose is 1.5 mg/m2 administered as an IV infusion over 24 hours through a central venous line every 21 days (3 weeks), until disease progression or unacceptable toxicity, in patients with normal bilirubin and AST or ALT less than or equal to 2.5 times the upper limit of normal. There is no recommended dose in patients with serum bilirubin levels above the institutional upper limit of normal.^58,59

Vistogard (uridine triacetate, Wellstat Therapeutics Corporation) was approved on December 11, 2015, for the emergency treatment of adults and pediatric patients following a fluorouracil or capecitabine overdose, regardless of the presence of symptoms; for patients who exhibit early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system; and for patients with early onset, unusually severe adverse reactions, such as gastrointestinal toxicity and neutropenia, within 96 hours following the end of fluorouracil or capecitabine administration.

Vistogard is not recommended for the nonemergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs. The safety and efficacy of Vistogard initiated more than 96 hours following the end of fluorouracil or capecitabine administration has not been established. The pyrimidine analog was granted orphan drug designation by the FDA.

Vistogard is available in 10-gram oral granule packets and can be administered without regard to meals. The recommended dosage in adults is 10 grams (1 packet) orally every 6 hours for 20 doses. In pediatric patients, the recommended dose is 6.2 grams/m2 of body surface area (not to exceed 10 grams per dose) orally every 6 hours for 20 doses.

Each dose should be mixed with 3 to 4 ounces of soft foods, such as applesauce, pudding, or yogurt and ingested within 30 minutes. The granules cannot be chewed and patients need to drink at least 4 ounces of water with each dose.^60,61

Docetaxel injection (Eagle Pharmaceuticals) was approved on December 28, 2015, in a non-alcohol formulation for the treatment of breast cancer, NSCLC, prostate cancer, gastric adenocarcinoma, and head and neck cancer. The non-alcohol taxane product is the first non-alcohol docetaxel formulation approved in the United States.

The need for an alcohol-free docetaxel gained visibility in June 2014 when the FDA issued a Drug Safety Communication warning patients that docetaxel may cause symptoms of alcohol intoxication after treatment. Docetaxel was originally developed by Sanofi and marketed under the Taxotere brand. Since its patent expired in 2011, several different generics entered the market.

Eagle Pharmaceuticals entered into an exclusive licensing agreement with Teikoku Pharma USA Inc in October 2015, to market, sell, and distribute docetaxel injection, non-alcohol in the United States. The non-alcohol formulation requires no prior dilution and is ready to add to the infusion solution. It is available in 3 different presentations: 20 mg/ml in single-dose vials and 80 mg/4-mL or 160 mg/8-mL in multiple-dose vials.⁶²

LATE BREAKING SPECIALTY FDA ACTIONS

Nucala (mepolizumab, GlaxoSmithKline), was approved on November 5, 2015, as an add-on maintenance treatment for patients with severe asthma, aged 12 and older, and with an eosinophilic phenotype. Nucala is approved for patients with a history of severe asthma attacks, despite receiving current asthma medications.

Nucala is not to be used for treatment of other eosinophilic conditions and not for relief of acute bronchospasm or status asthmaticus. Nucala is a humanized interleukin-5 antagonist monoclonal antibody (IgG1 kappa) produced by recombinant DNA technology. It is available in a single-dose vial containing 100 mg of lyophilized powder for reconstitution.

The recommended dose is 100 mg administered by a health care professional once every 4 weeks via subcutaneous injection into the upper arm, thigh, or abdomen. In line with clinical practice, monitoring of patients after administration of biologic agents is recommended.^63,64

Vonvendi (von Willebrand factor (recombinant), Baxalta Inc) was approved on December 8, 2015, for on-demand treatment and control of bleeding episodes in adults 18 years and older diagnosed with von Willebrand disease. Vonvendi was granted orphan drug designation for the above indications and is the first FDA-approved recombinant von Willebrand factor (VWF).

It is available as a lyophilized powder for IV infusion in single-use vials containing nominally 650 or 1300 IU VWF: Ristocetin Cofactor. The initial dosage is 40 to 80 IU per kg of body weight and the dosage should be adjusted according to the extent and location of the bleed.

For each bleeding episode, it is recommended that the first dose be administered with an approved recombinant (non-VWF containing) factor VIII, if factor VIII baseline levels are below 40%, or are unknown. If recombinant factor VIII is required, it should be given within 10 minutes of completing the Vonvendi infusion.^65,66

Kanuma (sebelipase alfa, Alexion Pharmaceuticals) was approved on December 8, 2015. The hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme is indicated for the treatment of patients with a diagnosis of lysosomal acid lipase (LAL) deficiency. The drug is available in 20-mg/10-mL (2-mg/ml) single-use vials of solution administered as an IV infusion by a health care provider.

The recommended dosage for patients with rapidly progressive LAL deficiency presented within the first 6 months of life is 1 mg/kg administered once weekly. For pediatric and adult patients with LAL deficiency, the recommended starting dosage is 1 mg/kg once every other week. Kanuma should be infused over a period of at least 2 hours.^67,68

Uptravi (selexipag, Actelion Pharmaceuticals) was approved on December 21, 2015, for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and to reduce the risk of hospitalization for PAH. The oral prostacyclin receptor agonist was granted orphan drug designation by the FDA.

Uptravi is available in a tablet form in strengths of 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1000 mcg, 1200 mcg, 1400 mcg, and 1600 mcg. The recommended starting dose is 200 mcg twice daily. The dosage can be increased by 200 mcg twice daily at weekly intervals to the highest tolerated dose of up to 1600 mcg twice daily. The maintenance dose is determined based on the patient’s tolerability.^69,70 SPT

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• FDA approves Darzalex for patients with previously treated multiple myeloma [news release]. US Food and Drug Administration; November 16, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm472875.htm. Accessed November 17, 2015,
• Ninlaro [package insert]. Cambridge, MA: Takeda Pharmaceutical Company Limited; 2015. http://www.ninlarohcp.com/downloads/Prescribing-Information.pdf. Published November 2015. Accessed December 8, 2015.
• FDA approves Ninlaro, new oral medication to treat multiple myeloma [news release]. US Food and Drug Administration; December 1, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm473771.htm. Accessed December 8, 2015.
• FDA approves Empliciti, a new immune-stimulating therapy to treat multiple myeloma [news release]. US Food and Drug Administration; December 22, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474684.htm. Accessed December 9, 2015.
• Empliciti [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2015. http://packageinserts.bms.com/pi/pi_empliciti.pdf. Published November 2015. Accessed December 9, 2015.
• FDA approves Novartis drug Odomzo (sonidegib) for locally advanced basal cell carcinoma (laBCC), a form of skin cancer [press release]. East Hanover, NJ: Novartis Pharmaceuticals; July 24, 2015. https://www.novartis.com/news/media-releases/fda-approves-novartis-drug-odomzo%C2%AE-sonidegib-locally-advanced-basal-cell. Accessed October 26, 2015.
• Odomzo [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2015. http://www.pharma.us.novartis.com/product/pi/pdf/odomzo.pdf. Published July 2015. Accessed October 26, 2015.
• FDA approves first-of-its-kind product for the treatment of melanoma [news release]. US Food and Drug Administration; October 27, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm469571.htm. Accessed November 6, 2015.
• Imlygic [package insert]. Thousand Oaks, CA: Amgen Inc; 2015. http://pi.amgen.com/united_states/imlygic/imlygic_pi.pdf. Published October 2015. Accessed November 6, 2015.
• FDA approves Yervoy to reduce the risk of melanoma returning after surgery [news release]. US Food and Drug Administration; October 28, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm469944.htm. Accessed November 7, 2015.
• Yervoy [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2015. http://packageinserts.bms.com/pi/pi_yervoy.pdf. Published October 2015. Accessed November 7, 2015.
• FDA approves Cotellic as part of combination treatment for advanced melanoma [news release]. US Food and Drug Administration; November 10, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471934.htm. Accessed November 17, 2015.
• Cotellic [package insert]. South San Francisco, CA: Genentech, Inc.; 2015. http://www.gene.com/download/pdf/cotellic_prescribing.pdf?cid=cob_PS_MBCOSC0008_1&c=MBCOSC0008&mkwid=sxEulKdi4_dc|pcrid|83876927904|pkw|cotellic|pmt|p&utm_source=google&utm_medium=cpc&utm_campaign=HCP+Branded+%7C+Cotellic+%7C+HCP+%7C+Branded+%7C+Cotellic.com+%7C+MMEL+%7C+cob_PS_MBCOSC0008_1&utm_term=cotellic Revised November 2015. Accessed November 17, 2015.
• FDA approves Opdivo to treat advanced form of kidney cancer [news release]. US Food and Drug Administration; November 23, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm473971.htm Published November 2015. Accessed December 9, 2015.
• FDA expands approved use of Opdivo to treat lung cancer [news release]. US Food and Drug Administration; March 4, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436534.htm. Accessed March 22, 2015.
• FDA expands approved use of Opdivo in advanced lung cancer: Opdivo demonstrates survival benefit in squamous and non-squamous non-small cell lung cancer [news release]. US Food and Drug Administration; October 9, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm466413.htm. Accessed November 5, 2015.
• Nivolumab in combination with ipilimumab. US Food and Drug Administration website. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm465274.htm. Updated October 1, 2015. Accessed November 5, 2015.
• Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2014. http://packageinserts.bms.com/pi/pi_opdivo.pdf. Published November 2015. Accessed December 9, 2015.
• Iressa [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2015. http://www.azpicentral.com/iressa/iressa.pdf#page=1. Published July 2015. Accessed October 6, 2015.
• Iressa approved by US FDA for first-line treatment of patients with advanced EGFR mutation-positive non-small cell lung cancer [press release]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; July 13, 2015. http://www.astrazeneca.com/Media/Press-releases/Article/20150713-iressa-approved-by-us-fda. Accessed October 6, 2015.
• Pembrolizumab label updated with new clinical trial information. US Food and Drug Administration website. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm478493.htm. Published December 18, 2015. Accessed January 6, 2016.
• FDA approves Keytruda for advanced non-small cell lung cancer [news release]. US Food and Drug Administration; October 2, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm465444.htm. Accessed November 5, 2015.
• Keytruda [package insert]. Whitehouse, Station, NJ: Merck & Co., Inc; 2015. http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. Published December 2015. Accessed January 6, 2015.
• FDA approves new pill to treat certain patients with non-small cell lung cancer [news release]. US Food and Drug Administration; November 13, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm472525.htm. Accessed November 17, 2015.
• Tagrisso [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208065s000lbl.pdf. Published November 2015. Accessed November 17, 2015.
• FDA approves Portrazza to treat advanced squamous non-small cell lung cancer [news release]. US Food and Drug Administration; November 24, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474131.htm. Accessed December 9, 2015.
• Portrazza [package insert]. Indianapolis, IN: Eli Lilly & Co; 2015. http://uspl.lilly.com/portrazza/portrazza.html#pi. Published November 2015. Accessed December 9, 2015.
• FDA approves new oral therapy to treat ALK-positive lung cancer [news release]. US Food and Drug Administration; December 11, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm476926.htm .Accessed January 4, 2016.
• Alecensa [package insert]. South San Francisco, CA: Genentech, Inc.; 2015. http://www.gene.com/download/pdf/alecensa_prescribing.pdf. Published December 2015. Accessed January 4, 2016.
• FDA approves Ibrance for postmenopausal women with advanced breast cancer [news release]. US Food and Drug Administration; February 3, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm432871.htm. Accessed March 20, 2015.
• Ibrance [package insert]. New York, NY: Pfizer Inc; 2015. http://labeling.pfizer.com/ShowLabeling.aspx?id=2191 Published February 2015. Accessed March 20, 2015.
• Lenvatinib (Lenvima). US Food and Drug Administration website. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm434347.htm. Published February 13, 2015. Accessed March 20, 2015.
• Lenvima [package insert]. Woodcliff Lake, NJ: Eisai Inc,; 2015. http://www.lenvima.com/pdfs/prescribing-information.pdf. Published February 2015. Accessed March 20, 2015.
• Zarxio [package insert]. Princeton, NJ: Sandoz Inc,; 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125553lbl.pdf. Published March 2015. Accessed March 22, 2015.
• FDA approves first biosimilar product Zarxio [news release]. US Food and Drug Administration; March 6, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm. Accessed March 22, 2015.
• Unituxin [package insert]. Silver Spring, MD: United Therapeutics Corporation; 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125516s000lbl.pdf. Published March 2015. Accessed March 23, 2015.
• FDA approves first therapy for high-risk neuroblastoma [news release]. US Food and Drug Administration; March 10, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm437460.htm Accessed March 23, 2015.
• Ramucirumab mCRC. US Food and Drug Administration website. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm444496.htm. Published April 2015. Accessed November 13, 2015.
• Cyramza [package insert]. Indianapolis, IN: Eli Lilly & Co; 2015. http://pi.lilly.com/us/cyramza-pi.pdf. Published April 2014. Accessed January 16, 2015.
• FDA Approves Cyramza for stomach cancer [news release]. US Food and Drug Administration; April 24, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394107.htm. Accessed April 25, 2015.
• FDA approves new drug treatment for nausea and vomiting from chemotherapy [news release]. US Food and Drug Administration; September 2, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm460838.htm. Accessed November 13, 2015.
• Varubi [package insert]. Waltham, MA: Tesaro, Inc.; 2015. http://varubirx.com/downloads/VARUBI_(rolapitant)_Full_Prescribing_Information_September_2015.pdf. Published September 2015. Accessed November 13, 2015.
• Lonsurf [package insert]. Princeton, NJ: Taiho Oncology, Inc.; 2015. https://www.taihooncology.com/us/prescribing-information.pdf. Published September 2015. Accessed November 3, 2015.
• FDA approves new oral medication to treat patients with advanced colorectal cancer [news release]. US Food and Drug Administration; September 22, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm463650.htm. Accessed November 3, 2015.
• FDA approves new treatment for advanced pancreatic cancer [new release]. US Food and Drug Administration; October 22, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468654.htm. Accessed November 6, 2015.
• Merrimack Pharmaceuticals. Onivyde [package insert]. Cambridge, MA: Merrimack Pharmaceuticals, Inc,; 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf. Published October 2015. Accessed November 6, 2015.
• FDA approves new therapy for certain types of advanced soft tissue sarcoma [news release]. US Food and Drug Administration; October 23, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468832.htm. Accessed November 6, 2015.
• Yondelis [package insert]. Horsham, PA: Janssen Biotech, Inc; 2015. http://www.yondelis.com/shared/product/yondelis/yondelis-prescribing-information.pdf. Published October 2015. Accessed November 6, 2015.
• FDA approves first emergency treatment for overdose of certain types of chemotherapy [news release]. US Food and Drug Administration; December 11, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm476919.htm. Accessed January 6, 2016.
• Vistogard [package insert]. Gaithersburg, MD: Wellstat Therapeutics Corporation; 2015. https://www.vistogard.com/Vistogard/media/Vistogard/Files/final-labeling-text-vistogard.pdf. Published December 2015. Accessed January 6, 2016.
• Teikoku Pharma USA Inc announces FDA approval of docetaxel injection, non-alcohol formula [press release]. San Jose, CA: PR Newswire website; December 28, 2015. http://www.prnewswire.com/news-releases/teikoku-pharma-usa-inc-announces-fda-approval-of-docetaxel-injection-non-alcohol-formula-300197304.html. Accessed January 3, 2016.
• FDA approves Nucala to treat severe asthma [news release]. US Food and Drug Administration; November 6, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471031.htm. Accessed November 7, 2015.
• Nucala [package insert]. Philadelphia, PA: GlaxoSmithKline; 2015. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Nucala/pdf/NUCALA-PI-PIL.PDF. Published November 2015. Accessed November 7, 2015.
• Vonvendi [package insert]. Westlake Village, CA: Baxalta US Inc.; 2015. http://baxalta.com/assets/documents/VONVENDI_PI.pdf. Published December 2015. Accessed December 21, 2015.
• FDA approves first recombinant von Willebrand factor to treat bleeding episodes [news release]. US Food and Drug Administration; December 8, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm476065.htm. Accessed December 21, 2015.
• FDA approves first drug to treat a rare enzyme disorder in pediatric and adult patients [news release]. US Food and Drug Administration; December 10, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm476013.htm. Accessed December 21, 2015.
• Kanuma [package insert]. Cheshire, CT: Alexion Pharmaceuticals; 2015. http://kanuma.com/docs/full-prescribing-information.pdf. Published December 2015. Accessed December 21, 2015.
• Uptravi [package insert]. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2015. https://www.uptravi.com/pdf/UPTRAVI-Full-Prescribing-Information.pdf. Published December 2015. Accessed January 6, 2016.
• FDA approves new orphan drug to treat pulmonary arterial hypertension [news release]. US Food and Drug Administration; December 12, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm478599.htm. Accessed January 6, 2016.

, has worked in both national specialty pharmacy and payer organizations and has experience in clinical management, adherence, and persistency programs, as well as chronic disease cost optimization strategies. Dr. Ness is active in the Consortium of Multiple Sclerosis Centers, Academy of Managed Care Pharmacy, National Home Infusion Association, National Association of Specialty Pharmacy, Specialty Pharmacy Certification Board, and Hematology and Oncology Pharmacy Association, and has served on the Minnesota Medicaid Drug Formulary Committee since 2008. She is a certified multiple sclerosis specialist, a credentialed HIV pharmacist, a Certified Specialty Pharmacist, and currently serves as the director of specialty clinical services at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey.

RUBY MHAJAN, RPH, currently serves as a clinical pharmacist at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey. Ruby has over 13 years of exceptional experience as a clinical pharmacist, having worked in both the United States and Canada in various settings including retail, long-term care, home infusion/specialty, and a national outsourcing admixture pharmacy. Most recently, she served as a Director of Pharmacy for a Home Infusion/Specialty Pharmacy in New York.