New Drugs 2014

NewCyramza for treatment of advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.

Cyramza (ramucirumab) - Lilly - Cyramza is a recombinant monoclonal antibody of the IgG1 class that binds to vascular endothelial growth factor receptor-2 (VEGFR2) and blocks the activation of the receptor. It is indicated in the treatment of gastric cancer (advanced gastric cancer or gastro-esophageal junction adenocarcinoma), as a single agent after prior fluoropyrimidine or platinum containing chemotherapy. The approval is based on the improved overall survival in multinational, randomized, double-blind, multicenter study (I4T-IE-JVBD) who enrolled 355 patients with previously treated advanced or metastatic, gastric or GEJ adenocarcinoma. They were randomized to receive Cyramza or placebo. The median overall survival was 5.2 months with Cyramza and 3.8 months with placebo. The most common adverse effects were hypertension and diarrhea and this was at a rate of ≥10% and ≥2% higher than placebo. The most common serious adverse events with Cyramza were intestinal obstruction (2.1%) and anemia (3.8%). Cyramza increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue Cyramza in patients who experience severe bleeding. Other important risks included in labeling are hemorrhage, arterial thrombotic events, impaired wound healing, clinical deterioration in patients with cirrhosis, and reversible posterior leukoencephalopathy. The recommended dose and schedule is 8mg/kg administered as a 60 minute IV infusion every 2 weeks.
Approved: April 2, 2014

NewEntyvio for ulcerative colitis and crohn’s disease.

Entyvio (vedolizumab) - Takeda - Entyvio is an injection for the treatment of adults with moderate to severe ulcerative colitis and moderate to severe Crohn‘s disease. Entyvio is approved to treat those conditions when 1 or more standard therapies (corticosteroids, immunomodulators, or tumor necrosis factor blockers) have not resulted in an adequate response. The safety and effectiveness of Entyvio for ulcerative colitis were established in 2 clinical trials involving approximately 900 patients who had not responded adequately to 1 or more standard therapies. Evaluations of patients included measures of stool frequency, rectal bleeding, endoscopic findings and a physician‘s overall assessment. Results showed a greater percentage of patients treated with Entyvio compared to a placebo achieved and maintained clinical response, achieved and maintained clinical remission, achieved corticosteroid-free clinical remission. The safety and effectiveness of Entyvio for Crohn‘s disease were established in 3 clinical trials involving approximately 1,500 patients. Results showed a greater percentage of patients treated with Entyvio compared to a placebo achieved clinical response, achieved clinical remission, and achieved corticosteroid-free clinical remission. Entyvio is an integrin receptor antagonist. Integrin receptors are proteins expressed on the surface of certain cells and they function as bridges for cell-cell interactions. Entyvio blocks the interaction of a specific integrin receptor with a specific protein and thereby blocks the migration of those circulating inflammatory cells across those blood vessels and into areas of inflammation in the gastrointestinal tract. The most common side effects in patients treated with Entyvio include headache, joint pain, nausea, and fever. The most serious risks associated with Entyvio include serious infections, hypersensitivity and infusion-related reactions; and hepatotoxicity.
Approved: May 20, 2014

NewFarxiga to treat adult type 2 diabetes.

Farxiga (dapaglifozin) - Bristol Meyers - Fargixa is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. SGLT2 inhibitors block the reabsorption of glucose by the kidney, increase glucose excretion, and lower blood glucose levels. The safety and effectiveness were evaluated in 16 clinical trials including more than 9,400 patients with type 2 diabetes. The trials showed improvement in HbA1c which is a measure of blood sugar control. Farxiga can be used alone or in combination with other type 2 diabetic medications. Farxiga should not be used to treat people with type 1 diabetes; those with diabetic ketoacidosis; or those with moderate or severe renal impairment, end stage renal disease, or patients on dialysis. An increased number of bladder cancers were diagnosed among Farxiga users in clinical trials, so Farxiga is not recommended for patients with active bladder cancer. Patients with a history of bladder cancer should talk to their physician before taking Farxiga. Farxiga can cause dehydration, leading to hypotension that can result in dizziness and/or fainting and a decline in renal function. The elderly, patients with impaired renal function, and patients on diuretics to treat other conditions appear to be more susceptible to this risk. Due to these adverse reactions, the FDA is requiring 6 post marketing studies for Farxiga. Farxiga is available in 5mg and 10mg tablets. The recommended starting dose is 5 mg once daily, taken in the morning, with or without food. The dose can be increased to 10 mg once daily in patients tolerating Farxiga who need additional glycemic control. Renal function needs to be assessed before therapy with Farxiga is initiated. Do not initiate Farxiga if eGFR is below 60 mL/min and discontinue use if eGFR falls persistently below 60. The most common side effects were female genital mycotic infections, nasopharyngitis, and urinary tract infections.

NewHetlioz to treat 24-hour sleep-wake disorder in totally blind individuals.

Hetlioz (tasimelteon) - Vanda - Hetlioz, a melatonin receptor agonist, has been approved to treat non-24- hour sleep-wake disorder (“non-24”) in totally blind individuals. This is the first FDA approved medication for the disorder. Non-24 is a chronic circadian rhythm (body clock) disorder in the blind that causes problems with the timing of sleep. Light does not enter their eyes and they cannot synchronize their body clock to the 24-hour light-dark cycle. Those with the disorder may have difficulty falling asleep or staying asleep, and may wake up groggy or feeling as if they need more rest. People with non-24 may find their sleep patterns reversed, therefore needing to sleep during the day and to be awake at night. The effectiveness of Hetlioz was evaluated in 104 participants in 2 clinical trials of totally blind individuals with non-24 disorder. The trials showed treatment with Hetlioz resulted in significant improvement compared to placebo, both in increasing nighttime sleep and decreasing daytime sleep duration. The dose is 20 mg prior to bedtime at same time every night. It is available as a 20mg capsule and should be taken without food. After taking Hetlioz, patients should limit their activity to preparing for going to bed, because Hetlioz can impair the performance of activities requiring complete mental alertness. The most common side effects were headache, increased alanine aminotransferase, nightmares or unusual dreams, and upper respiratory or urinary tract infection. Avoid use of Hetlioz in combination with strong CYP1A2 inhibitors because of increased exposure and strong CYP3A4 inducers because of decreased exposure.
Approved: January 31, 2014

NewImpavido to treat leishmaniasis.

Impavido (miltefosine) - Paladin - Impavido (miltefosine) is used to treat a tropical disease called leishmaniasis. Leishmaniasis is a disease caused by a parasite, Leishmania, which is transmitted to humans through sand fly bites. The disease occurs predominantly in people who live in the tropics and subtropics. Most U.S. patients acquire leishmaniasis while overseas. Impavido is an oral medicine approved to treat the 3 main types of leishmaniasis: visceral (affects internal organs), cutaneous (affects the skin) and mucosal (affects the nose and throat) in patients 12 years of age and older. Impavido is the first FDA approved drug to treat cutaneous or mucosal leishmaniasis, therefore the FDA granted Paladin with fast track designation, priority review, and orphan product designation. Impavido’s safety and efficacy were evaluated in 4 clinical trials with a total of 547 patients receiving Impavido and 183 patients receiving either a comparator drug or a placebo. Results from these trials demonstrated that Impavido is safe and effective in treating visceral, cutaneous and mucosal leishmaniasis. The labeling for Impavido contains a boxed warning to alert patients and health care professionals that the drug can cause fetal harm and therefore should not be given to pregnant women. Health care professionals should advise women to use effective contraception during and for five months after Impavido therapy. The most common side effects in clinical trials were nausea, vomiting, diarrhea, headache, decreased appetite, dizziness, abdominal pain, itching, drowsiness and elevated levels of liver enzymes (transaminases) and creatinine. Impavido is available as a 50 mg capsule and should be given with food to improve GI side effects. For 30 to 44 kg give 50 mg twice daily for 28 days and for 45 kg or > give 50 mg 3 times daily for 28 days.
Approved: March 19, 2014

NewMyalept to treat complications of leptin deficiency.

Myalept (metreleptin) - Amylin - Myalept is a leptin analog used as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. Lipodystrophy is a condition associated with the lack of fat tissue. Patients with congenital lipodystrophy are born with little or no fat tissue and they generally lose fat tissue over a period of time. Because the hormone leptin is made by fat tissue, patients with lipodystrophy have very low leptin levels. Leptin regulates food intake and other hormones, such as insulin. These patients often develop severe insulin resistance at a young age and may have diabetes mellitus that is difficult to control or hypertriglyceridemia that can lead to inflammation of the pancreas. The safety and effectiveness of Myalept was evaluated in an open-label, single-arm study that included 48 patients with congenital or acquired generalized lipodystrophy who also had diabetes mellitus, hypertriglyceridemia, and/or elevated levels of fasting insulin. The trial showed reductions in HbA1c, fasting glucose, and triglycerides. Myalept is available as an injection used once daily after reconstitution. Because of the risks associated with the development of neutralizing antibodies and lymphoma, Myalept is available only through the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program. Under this REMS program, prescribers must be certified and complete training. Pharmacies must be certified also and only dispense Myalept after receipt of the Myalept REMS Prescription Authorization Form for each new prescription. Myalept is contraindicated in patients with general obesity. Myalept is not approved for patients with HIV-related lipodystrophy or in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of generalized lipodystrophy. The recommended daily dose is based on body weight: <= 40 kg start at 0.06 mg/kg/day and increase or decrease by 0.02 mg/kg to maximum daily dose of 0.13 mg/kg. Males > 40 kg body weight start at a dose of 2.5 mg/day and increase or decrease by 1.25 mg to 2.5 mg/day to a maximum dose of 10 mg/day. Females > than 40 kg body weight start at a dose of 5 mg/day and increase or decrease by 1.25 mg to 2.5 mg/day to a maximum dose of 10 mg/day. The most common side effects include low blood sugar, headache, decreased weight, and abdominal pain.
Approved: February 24, 2014

NewNeuraceq used for PET imaging of the brain.

Neuraceq (florbetaben F 18) - Piramal Imaging - Neuraceq is a radioactive diagnostic agent indicated for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s Disease (AD) and other causes of cognitive decline. Following intravenous administration, Neuraceq crosses the blood brain barrier and shows differential retention in brain regions that contain β-amyloid deposits. Differences in signal intensity between brain regions showing specific and nonspecific Neuraceq uptake form the basis for the image interpretation method. A negative Neuraceq scan indicates sparse to no neuritic plaques and is inconsistent with a neuropathological diagnosis of AD at the time of image acquisition; a negative scan result reduces the likelihood that a patient’s cognitive impairment is due to AD. A positive Neuraceq scan indicates moderate to frequent amyloid neuritic plaques; neuropathological examination has shown this amount of amyloid neuritic plaque is present in patients with AD, but may also be present in patients with other types of neurologic conditions as well as older people with normal cognition. Neuraceq is used in adjunct to other diagnostic evaluations. Neuraceq is supplied in a 30 mL glass vial containing up to 30 mL of clear solution at a strength of 50 to 5000 MBq/mL florbetaben F18 at EOS. Each vial contains multiple doses and is enclosed in a shielded container to minimize external radiation exposure. No serious adverse reactions related to Neuraceq administration have been reported. The most common side effects were injection site reactions consisting of erythema, irritation and pain. All adverse reactions were mild to moderate in severity and of short duration.
Approved: March 19, 2014

NewNorthera to treat neurogenic orthostatic hypotension.

Northera (droxidopa) - Chelsea Therapeutics - Northera has been approved for the treatment of neurogenic orthostatic hypotension. NOH is a rare, chronic and often debilitating drop in blood pressure that occurs upon standing and is associated with Parkinson's disease, multiple-system atrophy, and pure autonomic failure. The FDA has approved Northera under the accelerated approval program which provides patient access to new drugs while the company conducts post-approval clinical trials to prove the drug’s clinical benefit. Northera also received orphan-product designation from the FDA because it is intended to treat a rare disease or condition. The effectiveness of Northera was shown in 2 clinical trials in patients with NOH through a 2 week period. Patients taking Northera reported a decrease in dizziness, lightheadedness, feeling faint, or feeling as if they might black out as compared with those taking placebo. Improvement in patient symptoms beyond two weeks has not been demonstrated. Northera is available in a 100mg, 200mg, and 300mg capsule. The starting dose is 100 mg 3 times daily to titrate by 100 mg 3 times daily, up to a maximum dose of 600 mg 3 times daily. Northera can be taken with or without food. Northera has a boxed warning to alert health care professionals and patients about the risk of supine hypertension, a common problem that affects people with primary autonomic failure and can cause stroke. It is essential that patients be reminded that they must sleep with their head and upper body elevated. Supine blood pressure should be monitored prior to and during treatment and more frequently when increasing doses. The most common side effects include headache, dizziness, nausea, hypertension and fatigue.
Approved: February 18, 2014

NewOtezla to treat psoriatic arthritis.

Otezla (apremilast) - Celgene - Otezla is an inhibitor of phosphodieasterase-4 and it is approved to treat adults with active psoriatic arthritis. The safety and effectiveness of Otezla were evaluated in 3 clinical trials involving almost 1500 patients with active psoriatic arthritis. Patients treated with Otezla showed improvement in their signs and symptoms, including tender and swollen joints and physical function, as compared to placebo. Patients treated with Otezla should be weighed by their physician regularly, and if there is unexplained or clinically significant weight loss the discontinuation of treatment should be considered. Treatment with Otezla was also associated with an increase in occurrence of depression compared to placebo. The FDA is requiring a pregnancy exposure registry as a post-marketing requirement to assess the risk to pregnant women related to Otezla exposure. The most common side effects were diarrhea, nausea, and headache. To reduce the risk of GI symptoms, titrate over a 6 day period to recommended dose of 30 mg twice daily. The dosage in severe renal impairment is decreased to just 30 mg once daily. Otezla is available in 10 mg, 20 mg, and 30 mg tablets.
Approved: March 21, 2014

NewSylvant for treatment of Castleman’s disease.

Sylvant (siltuximab) - Janssen - Sylvant has been approved to treat patients with multicentric Castleman’s disease (MCD), a rare disorder similar to lymphoma. MCD causes an abnormal overgrowth of immune cells in lymph nodes and related tissues in the body. The disease usually affects adults who suffer from fever, night sweats, weight loss and weakness or fatigue because their body’s immune system is weakened and cannot fight infections. Sylvant is an injection that works by blocking a protein that stimulates abnormal growth of immune cells. It is intended for patients with MCD who do not have HIV or human herpes virus 8 (HHV-8). The FDA reviewed Sylvant under its priority review program, which provides an expedited review for drugs that demonstrate the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Sylvant was also granted orphan product designation because it is being used to treat a rare disease or condition. Sylvant’s safety and effectiveness were evaluated in a clinical trial of 79 patients with MCD who were HIV and HHV-8 negative. Patients were randomly assigned to receive a combination of Sylvant and best supportive care, or placebo and best supportive care. Results showed 34 percent of patients treated with Sylvant and best supportive care experienced tumor response, while no patient treated with placebo and best supportive care did. Common side effects include pruritis, weight gain, rash, increased levels of uric acid in the blood and upper respiratory tract infection. Sylvant is for intravenous infusion only and administered as an 11 mg/kg dose given over 1 hour every 3 weeks. Sylvant is available in a 100 mg or 400 mg single dose vial.
Approved: April 23, 2014

NewTanzeum for treatment of type 2 diabetes.

Tanzeum (albiglutide) - GSK - Tanzeum is approved for subcutaneous injection to improve glycemic control, along with diet and exercise, in adults with type 2 diabetes. Tanzeum is a glucagon-like-peptide-1 receptor agonist, which is a hormone that helps regulate blood sugar levels. The drug’s safety and effectiveness were evaluated in 8 clinical trials, which included more than 2,000 patients with type 2 diabetes. The trials showed that the patients had an improvement in their HbA1c level. Tanzeum can be used alone or in combination with other drugs, including metformin, glimepiride, pioglitazone, and insulin. It should not be used to treat type 1 diabetes; in those who have diabetic ketoacidosis; or as first line therapy for patients adequately controlled on diet and exercise. Do not use Tanzeum in patients with a history of pancreatitis or pre-existing severe gastrointestinal disease. Tanzeum is administered once weekly at any time of day, without regard to meals. It is injected SQ into the abdomen, thigh, or upper arm with an initial dose of 30 mg. Dose can be increased to 50 mg once weekly in patients requiring additional glycemic control. It is available in a 30 or 50 mg single-dose pen. The most common side effects include upper respiratory tract infection, diarrhea, nausea, and injection site reaction. Tanzeum has a black box warning included for a risk of thyroid C-cell tumors. The FDA is requiring post-marketing studies for: use in pediatrics; a medullary thyroid carcinoma (MTC) case registry for 15 years; and a cardiovascular outcomes trial (CVOT) to evaluate cardiovascular risks in patients with high baseline risk of cardiovascular disease.
Approved: April 15, 2014

NewVimizim for treatment of mucopolysaccharidosis type IVA.

Vimizim (elosulfase alfa) - BioMarin - Vimizim is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). The safety and efficacy of Vimizim were evaluated in a 24 week, randomized, double-blind, placebo-controlled clinical trial of 176 patients with MPS IVA. The majority of the patients (82%) presented with a medical history of musculoskeletal conditions, which included knee deformity (52%), kyphosis (31%), hip dysplasia (22%), prior spinal fusion surgery (22%) and arthralgia (20%). At baseline, all enrolled patients could walk more than 30 meters but less than 325 m in 6 minutes. Patients received Vimizim 2 mg/kg once per week, Vimizim 2 mg/kg once every other week, or placebo. The primary endpoint was the change from baseline in the distance walked in 6 minutes at Week 24. The other endpoints included changes from baseline in the rate of stair climbing in 3 minutes and changes from baseline in urine KS levels at Week 24. The treatment effect in the distance walked in 6 minutes, compared to placebo, was 22.5 m in patients who received Vimizim 2 mg/kg once per week. There was no difference in the rate of stair climbing between patients who received Vimizim 2 mg/kg once per week and those who received placebo. Patients who received Vimizim 2 mg/kg once every other week performed similarly in the 6-MWT and 3-MSCT as those who received placebo. The reduction in urinary KS levels from baseline, a measure of pharmacodynamic effect, was greater in the Vimizim treatment groups compared to placebo. The relationship between urinary KS and other measures of clinical response has not been established. The most common side effects were pyrexia, vomiting, headache, nausea, abdominal pain, chills, and fatigue. The recommended dose is 2 mg per kg given IV over 3.5 to 4.5 hours, based on infusion volume, once a week. Pre-treatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the infusion. Vimizim is available in a (1 mg/ml) 5 ml single dose vial and should be stored under refrigeration at 2°C to 8°C. Must be diluted prior to use.
Approved: February 14, 2014

NewZontivity for cardiovascular risk reduction.

Zontivity (vorapaxar) - Merck - Zontivity is approved for high risk patients (previous heart attack or peripheral artery disease) to reduce the risk of heart attack, stroke, cardiovascular death, and need for procedures to restore blood flow to the heart. Zontivity is the first in a new class of drug, called a protease-activated receptor-1 antagonist (PAR-1). It is an anti-platelet drug, designed to decrease the tendency of platelets to clump together and form a clot, which will decrease the risk of heart attack and stroke. Zontivity will increase the risk of bleeding which can be life threatening. This will be included on the label as a Boxed Warning to alert health care professionals. It is contraindicated in people who have had a stroke, TIA, or bleeding in the head, because the risk of bleeding in the head is increased. In clinical trials, Zontivity lowered the risk of heart attack, stroke, and cardiovascular death in high risk patients from 9.5% to 7.9% over a 3 year period. The most common side effects are bleeding, GI bleeding, anemia, and depression.
Approved: May 8, 2014

NewZykadia for treatment of metastatic non-small cell lung cancer.

Zykadia (ceritinib) - Novartis -Zykadia is approved as a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The safety of Zykadia was based on 255 patients with ALK positive tumors who received Zykadia at a dose of 750 mg orally once daily. The most common adverse reactions (>or=25%) were diarrhea, nausea, transaminitis, vomiting, abdominal pain, fatigue, decreased appetite and constipation. The most common CTCAE grade 3-4 adverse reactions (>or=5%) were diarrhea, fatigue, transaminitis, hyperglycemia, hypophosphatemia, increased lipase levels, and anemia. Other serious adverse reactions include interstitial lung disease and QT prolongation. The recommended dose of Zykadia is 750 mg once daily on an empty stomach until disease progression or unacceptable toxicity. Zykadia is available in a 150 mg capsule.
Approved: April 29, 2014