New Drugs 2015
Cholbam to treat rare bile acid synthesis disorders
Cholbam (cholic acid) – Asklepion – The FDA approved Cholbam (cholic acid) capsules, the first FDA approved treatment for pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders (including Zellweger spectrum disorders). Patients with these rare, genetic, metabolic conditions exhibit manifestations of liver disease, steatorrhea (presence of fat in the stool) and complications from decreased fat-soluble vitamin absorption. Cholbam is approved as an oral treatment for children aged three weeks and older, and adults. The manufacturer of Cholbam was granted a rare pediatric disease priority review voucher–a provision that encourages development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. The efficacy of Cholbam for the treatment of patients with bile acid synthesis disorders due to single enzyme defects was assessed in a single arm trial involving 50 patients treated over an 18 year period. An extension trial followed 21 of these patients and enrolled an additional 12 patients with short-term efficacy data available for an additional 21 months. On average, patients were 4 years of age at the start of cholic acid treatment. Response to treatment was evaluated by improvements in baseline liver function tests and weight. Responses were noted in 64 percent of patients with evaluable data. Two-thirds of patients survived greater than three years. The efficacy of Cholbam for the treatment of peroxisomal disorders, including Zellweger spectrum disorders, was assessed in a single arm, treatment trial involving 29 patients treated over an 18 year period. An extension trial followed 10 of these patients and enrolled an additional 2 patients with interim efficacy data available for 21 additional months. The majority of patients were less than 2 years of age at the start of cholic acid treatment. Response to treatment was evaluated by improvements in baseline liver function tests and weight. Responses were noted in 46 percent of patients with evaluable data. Forty-two percent of patients survived greater than 3 years. Cholbam’s effects on other manifestations of bile acid disorders due to single enzyme defects or peroxisomal disorders, such as neurologic symptoms, have not been established. The most common adverse effect in patients treated with Cholbam was diarrhea. The use of Cholbam should be carefully monitored by an experienced hepatologist or pediatric gastroenterologist, and treatment discontinued in patients developing worsening liver function.
Approved: March 17, 2015.
Unituxin for high-risk neuroblastoma
Unituxin (dinutuximab) – United Therapeutics - The FDA has approved Unituxin as part of first-line therapy for pediatric patients with high-risk neuroblastoma, a type of cancer that most often occurs in young children. Unituxin is an antibody that binds to the surface of neuroblastoma cells. Unituxin is being approved for use as part of a multimodality treatment, including surgery, chemotherapy and radiation therapy for patients who achieved at least a partial response to prior first-line multi-agent, multimodality therapy. The safety and efficacy of Unituxin were evaluated in a clinical trial of 226 pediatric patients with high-risk neuroblastoma whose tumors shrunk or disappeared after treatment with multiple-drug chemotherapy and surgery followed by additional intensive chemotherapy and who subsequently received bone marrow transplantation support and radiation therapy. Patients were randomly assigned to receive either an oral retinoid drug, isotretinoin (RA), or Unituxin in combination with interleukin-2 and granulocyte-macrophage colony-stimulating factor, which are thought to enhance the activity of Unituxin by stimulating the immune system, and RA. Three years after treatment assignment, 63 percent of patients receiving the Unituxin combination were alive and free of tumor growth or recurrence, compared to 46 percent of patients treated with RA alone. In an updated analysis of survival, 73 percent of patients who received the Unituxin combination were alive compared with 58 percent of those receiving RA alone. Unituxin has a Boxed Warning alerting patients and health care professionals that Unituxin irritates nerve cells, causing severe pain that requires treatment with intravenous narcotics and can also cause nerve damage and life-threatening infusion reactions, including upper airway swelling, difficulty breathing, and low blood pressure, during or shortly following completion of the infusion. Unituxin may also cause other serious side effects including infections, eye problems, electrolyte abnormalities and bone marrow suppression. The most common adverse effects of Unituxin were severe pain, fever, low platelet counts, infusion reactions, low blood pressure, hyponatremia, elevated liver enzymes, anemia, vomiting, diarrhea, low potassium levels in the blood, capillary leak syndrome, neutropenia and lymphopenia, hives, and low blood calcium levels. Unituxin is supplied in a carton containing one 17.5 mg/5 mL (3.5 mg/mL) single-use vial. Store Unituxin vials under refrigeration at 2°C to 8°C until time of use.
Approved: March 10, 2015.
Cresemba a new antifungal drug
Cresemba (isavuconazonium sulfate) - Astellas Pharma - The FDA has approved Cresemba, a new antifungal drug product used to treat adults with invasive aspergillosis and invasive mucormycosis, rare but serious infections. Cresemba belongs to a class of drugs called azole antifungal agents, which target the cell membrane of a fungus. The approval of Cresemba to treat invasive aspergillosis was based on a clinical trial involving 516 patients randomly assigned to receive either Cresemba or voriconazole. Cresemba’s approval to treat invasive mucormycosis was based on a single-arm clinical trial involving 37 patients treated with Cresemba and compared with the natural disease progression associated with untreated mucormycosis. Both studies showed Cresemba was safe and effective in treating these serious fungal infections. The most common adverse effects associated with Cresemba include nausea, vomiting, diarrhea, headache, abnormal liver blood tests, low potassium levels in the blood (hypokalemia), constipation, shortness of breath (dyspnea), coughing and tissue swelling (peripheral edema). Cresemba may also cause serious side effects including liver problems, infusion reactions and severe allergic and skin reactions. Cresemba is available in oral and intravenous formulations.
Approved: March 6, 2015.
Avycaz new antibacterial drug product
Avycaz (ceftazidime-avibactam) – Forest Pharmaceuticals – The FDA has approved Avycaz, a new antibacterial drug, to treat patients with complicated intra-abdominal infections, including kidney infections, who have limited or no alternative treatment options. The efficacy of Avycaz was supported by the findings of the efficacy and safety of ceftazidime for the treatment of cIAI and cUTI. The contribution of avibactam to Avycaz was based on data from in vitro studies and animal models of infection. Avycaz was studied in 2 Phase 2 trials. Both were not designed with any recognized hypothesis for inferential testing against any active comparators. Avycav for injection is supplied in a single use, clear glass vial. Each vial contains 2 grams ceftazidime and 0.5 grams avibactam. Avycaz vials should be stored at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). The most common adverse effects include vomiting, nausea, constipation, and anxiety. Patients should be informed of these risks and should also be advised that decreased efficacy, seizures and other neurologic events can be seen in patients with renal impairment. Serious skin reactions and anaphylaxis may occur in patients who are allergic to penicillin.
Approved: February 25, 2015.
Farydak for treatment of multiple myeloma
Farydak (panobinostat) – Novartis - The FDA approved Farydak for the treatment of patients with multiple myeloma. Multiple myeloma causes plasma cells to rapidly multiply and crowd out other healthy blood cells from the bone marrow. When the bone marrow has too many plasma cells, the cells may move to other parts of the body, which can weaken the body’s immune system, lead to anemia and cause other bone and kidney problems. Farydak works by inhibiting the activity of enzymes, known as histone deacetylases (HDACs). This process may hinder the over-development of plasma cells in multiple myeloma patients or cause these dangerous cells to die. Farydak is the first HDAC inhibitor approved to treat multiple myeloma. It is intended for patients who have received at least 2 prior standard therapies, including bortezomib and an immunomodulatory agent. Farydak is to be used in combination with bortezomib, a type of chemotherapy, and dexamethasone, an anti-inflammatory medication. The safety and efficacy of Farydak in combination with bortezomib and dexamethasone was demonstrated in 193 clinical trial patients with multiple myeloma who received at least 2 prior treatments that included bortezomib and an immunomodulatory agent. Patients were randomly assigned to receive a combination of Farydak, bortezomib and dexamethasone, or bortezomib and dexamethasone alone. Study results showed patients receiving the Farydak combination saw a delay in their disease progression for about 10.6 months, compared to 5.8 months in patients treated with bortezomib and dexamethasone alone. Additionally, 59 percent of Farydak-treated patients saw their cancer shrink or disappear after treatment, versus 41 percent in those receiving bortezomib and dexamethasone. Farydak has a Boxed Warning alerting patients and health care professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias and electrocardiogram changes have happened in patients receiving Farydak. Because of these risks, Farydak is being approved with a REMS consisting of a communication plan to alert health care professionals of these risks and how to minimize them. The most common adverse effects of Farydak were diarrhea, tiredness, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting and weakness. The most common laboratory abnormalities were hypophosphatemia, hypokalemia, hyponatremia, increased creatinine, thrombocytopenia, leukopenia and anemia. Healthcare professionals should also advise patients of the risk of bleeding in the GI tract and the lungs, and hepatotoxicity.
Approved: February 23, 2015.
Lenvima for thyroid cancer
Lenvima (lenvatinib) - Eisai - The FDA has granted approval to Lenvima to treat patients with progressive, differentiated thyroid cancer whose disease progressed despite receiving radioactive iodine therapy. The most common type of thyroid cancer, DTC is a cancerous growth of the thyroid gland which is located in the neck and helps regulate the body’s metabolism. The National Cancer Institute estimates that 62,980 Americans were diagnosed with thyroid cancer and 1,890 died from the disease in 2014. Lenvima is a kinase inhibitor, which works by blocking certain proteins from helping cancer cells grow and divide. Lenvima was approved approximately two months ahead of schedule. Lenvima’s efficacy was demonstrated in 392 patients with progressive, radioactive iodine-refractory DTC who were randomly assigned to receive either Lenvima or a placebo. Results showed Lenvima-treated patients lived a median of 18.3 months without their disease progressing, compared to a median of 3.6 months for patients who received a placebo. Additionally, 65 percent of patients treated with Lenvima saw a reduction in tumor size, compared to the 2 percent of patients who received a placebo. A majority of patients randomly assigned to receive the placebo were treated with Lenvima upon disease progression. The most common adverse effects of Lenvima were hypertension, fatigue, diarrhea, joint and muscle pain, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, swelling and pain in the palms, hands and/or the soles of the feet, abdominal pain and changes in voice volume or quality. Lenvima may cause serious adverse effects, including cardiac failure, arterial thromboembolic events, hepatotoxicity, renal failure and impairment, gastrointestinal perforation or a fistula formation, QT Interval Prolongation, hypocalcaemia, the simultaneous occurrence of headache, confusion, seizures and visual changes, hemorrhage, risks to an unborn child if a patient becomes pregnant during treatment, and impairing suppression of the production of thyroid-stimulating hormone.
Approved: February 13, 2015.
Ibrance for postmenopausal women with advanced breast cancer
Ibrance (palbociclib) – Pfizer - The FDA granted accelerated approval to Ibrance to treat metastatic breast cancer. Ibrance works by inhibiting molecules, known as cyclin-dependent kinases (CDKs) 4 and 6, involved in promoting the growth of cancer cells. Ibrance is intended for postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have not yet received an endocrine-based therapy. It is to be used in combination with letrozole. The FDA granted Ibrance breakthrough therapy designation because the sponsor demonstrated that the drug may offer a considerable improvement over available therapies. It also received a priority review, which provides for an expedited review of drugs intended to provide a significant improvement in safety or effectiveness in the treatment of a serious condition or meet an unmet medical need. Ibrance was approved more than two months ahead of schedule. The drug’s efficacy was proven in 165 postmenopausal patients with ER-positive, HER2-negative advanced breast cancer who had not received previous treatment for advanced disease. Clinical study patients were randomly assigned to receive Ibrance in combination with letrozole or letrozole alone. Patients treated with Ibrance plus letrozole lived about 20.2 months without their disease progressing, compared to about 10.2 months seen in patients receiving only letrozole. Information on overall survival is not available at this time. The most common adverse effects were a decrease in neutrophils (neutropenia), low levels of white blood cells (leukopenia), fatigue, anemia, upper respiratory infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy and nosebleed. Healthcare professionals should inform patients of these risks. It is recommended that treatment begin with a 125 mg dose for 21 days, followed by 7 days without treatment. Healthcare professionals are advised to monitor complete blood count prior to start of therapy and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated.
Approved: February 3, 2015.
Natpara to control low blood calcium levels in patients with hypoparathyroidism
Natpara (parathyroid hormone) - NPS Pharmaceuticals - The FDA approved Natpara (parathyroid hormone) to control hypocalcaemia in patients with hypoparathyroidism, a rare disease that affects approximately 60,000 people in the United States. Hypoparathyroidism is caused by loss of function of the parathyroid glands and occurs most commonly as a result of surgical removal of the parathyroid glands and more rarely as a result of autoimmune or congenital diseases. Patients with hypoparathyroidism can experience numbness, tingling, muscle twitching, spasms or cramps, abnormal heart rhythm, and seizures as a consequence of low blood calcium levels. Hypoparathyroidism is also associated with long-term complications such as kidney damage, kidney stones, development of cataracts and calcification of soft tissues. Natpara, a hormonal injection administered once daily, helps to regulate the body’s calcium levels. The FDA granted Natpara orphan drug designation because it is intended to treat a rare disease. The safety and effectiveness of Natpara were evaluated in a clinical trial of 124 patients who were randomly assigned to receive Natpara or a placebo. The trial was designed to determine whether Natpara can be used as a substitute for, or be used to help reduce the amount of, vitamin D or oral calcium taken by patients. Results showed 42 percent of Natpara-treated patients achieved normal blood calcium levels on reduced doses of calcium supplements and vitamin D, compared to 3 percent of placebo-treated patients. Natpara has a boxed warning that bone cancer has been observed in rat studies with Natpara. It is unknown whether Natpara causes bone cancer in humans, but because of this risk, Natpara is only recommended for use in patients whose hypocalcaemia cannot be controlled on calcium supplementation and vitamin D, and for whom the benefits outweigh this risk. Natpara is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). The most common adverse effects observed in Natpara-treated participants were sensations of tingling, tickling, pricking, or burning of the skin, low blood calcium, headache, high blood calcium, and nausea.
Approved: January 23, 2015.
Cosentyx to treat moderate to severe plaque psoriasis
Cosentyx (secukinumab) – Novartis – The FDA approved Cosentyx to treat adults with moderate-to-severe plaque psoriasis. Cosentyx is an antibody that binds to a protein (interleukin (IL)-17A) which is involved in inflammation. By binding to IL-17A, Cosentyx prevents it from binding to its receptor, and inhibits its ability to trigger the inflammatory response that plays a role in the development of plaque psoriasis. Cosentyx is administered as an injection under the skin and is intended for patients who are candidates for systemic therapy, phototherapy, or a combination of both. Safety and efficacy was established in 4 clinical trials with a total of 2,403 patients with plaque psoriasis who were candidates for phototherapy or systemic therapy. Patients were randomly assigned to receive Cosentyx or a placebo. The results showed that Cosentyx achieved greater clinical response than placebo, with skin that was clear or almost clear, as assessed by scoring of the extent, nature and severity of psoriatic changes of the skin. Cosentyx is being approved with a Medication Guide to inform patients that, because Cosentyx is a medicine that affects the immune system, patients may have a greater risk of getting an infection. Serious allergic reactions have been reported with the use of Cosentyx. Caution should be exercised when considering the use of Cosentyx in patients with a chronic infection or history of recurrent infection, and in patients with active Crohn’s Disease. The most common adverse reactions include diarrhea and upper respiratory infections.
Approved: January 21, 2015.
Savaysa to reduce risk of stroke and blood clots
Savaysa (edoxaban) - Daiichi Sankyo - The FDA has approved the anti-clotting drug Savaysa to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation that is not caused by a heart valve problem. Savaysa also has been approved to treat deep vein thrombosis and pulmonary embolism in patients who have already been treated with an anti-clotting drug administered by injection or infusion, for 5 to 10 days. The safety and efficacy of Savaysa in treating patients with atrial fibrillation not caused by cardiac valve disease was studied in a clinical trial of 21,105 patients. The trial compared 2 dose levels of Savaysa with warfarin for their effects on rates of stroke and systemic emboli. The trial results showed the higher dose of Savaysa to be similar to warfarin for the reduction in the risk of stroke. Warfarin is highly effective in reducing the risk of stroke in patients with atrial fibrillation, but increases the risk of bleeding. Savaysa demonstrated significantly less major bleeding compared with warfarin. In a clinical trial with 8,292 patients, Savaysa was studied in the treatment of DVT and PE. The study compared the safety and efficacy of Savaysa to warfarin in treating patients with a DVT and/or PE to reduce the rate of recurrence of symptomatic venous thromboembolism (VTE) events. In the trial, 3.2 percent of patients taking Savaysa had a symptomatic recurrent VTE compared to 3.5 percent of those taking warfarin. The most common adverse effects were bleeding and anemia. As with other FDA-approved anti-clotting drugs, bleeding, including life-threatening bleeding, is the most serious risk with Savaysa. Currently there is no treatment that has been proven to reverse the anti-coagulant effect of Savaysa. Savaysa has a Boxed Warning that provides important dosing and safety information for health care professionals about specific patient groups, including a warning that Savaysa is less effective in atrial fibrillation patients with a creatinine clearance greater than 95 milliliters per minute. This should be assessed before initiating therapy with Savaysa. Patients with creatinine clearance greater than 95 milliliters per minute have an increased risk of stroke compared to similar patients given warfarin. Savaysa should not be used in nonvalvular atrial fibrillation patients with a higher creatinine clearance.
Approved: January 8, 2015.