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P T. 2015;40(3): 152-156, 162-164, 168-171, 182

New Drugs/Drug News/New Medical Devices March 2015


Ibrance for Breast Cancer

Palbociclib (Ibrance, Pfizer) has received the FDA’s accelerated approval to treat postmenopausal women with estrogen receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer. The treatment is meant to be used in combination with letrozole (Femara, Novartis) for patients who have not received an endocrine-based therapy.

Palbociclib works by inhibiting cyclin-dependent kinases 4 and 6, which are involved in promoting the growth of cancer cells. The FDA granted the medication breakthrough and priority review status and approved it more than two months ahead of the prescription drug user fee goal date of April 13, 2015.

Palbociclib’s efficacy was demonstrated in 165 postmenopausal women with estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer who had not received previous treatment for advanced disease. Participants were randomly assigned to receive either palbociclib in combination with letrozole or letrozole alone. Progression-free survival among participants treated with palbociclib plus letrozole was 20.2 months, compared with approximately 10.2 months in those receiving only letrozole.

The most common side effects of treatment with palbociclib included neutropenia, leukopenia, fatigue, anemia, upper respiratory tract infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy, and epistaxis.

Recommendations call for treatment to begin with a 125-mg dose for 21 days, followed by seven days without treatment. Health care professionals are advised to monitor the complete blood count before the start of therapy and at the beginning of each cycle, as well as on day 14 of the first two cycles and as clinically indicated.

Source: FDA, February 3, 2015

Glyxambi for Type-2 Diabetes

The FDA has approved empagliflozin/linagliptin (Glyxambi, Boehringer Ingelheim/Eli Lilly) as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes when both empagliflozin and linagliptin are appropriate treatments.

Empagliflozin/linagliptin combines the mechanisms of action of a sodium glucose cotransporter 2 (SGLT2) inhibitor and a dipeptidyl peptidase 4 (DPP4) inhibitor in a once-daily tablet taken in the morning. SGLT2 inhibitors remove glucose through the urine by blocking blood glucose reabsorption in the kidney. DPP4 inhibitors increase hormones that stimulate the pancreas to produce more insulin and stimulate the liver to produce less glucose.

Empagliflozin/linagliptin is available in 10/5 mg or 25/5 mg dosages. It is not recommended for the treatment of type-1 diabetes or diabetic ketoacidosis.

The FDA’s approval was based on a phase 3 trial that evaluated the efficacy and safety of empagliflozin/linagliptin (10/5 mg and 25/5 mg) compared with the individual components of empagliflozin (10 mg or 25 mg) or linagliptin (5 mg) in adults who were also receiving high-dose metformin (mean dose, 1,889 mg daily). The study included 686 adults with type-2 diabetes and hemoglobin A1C (HbA1C) between 7.0% and 10.5% (mean at baseline, approximately 8.0%).

After using empagliflozin/linagliptin as an add-on to metformin for 24 weeks, participants achieved a mean HbA1C of 6.9% and 6.7% with empagliflozin/linagliptin 10/5 mg and 25/5 mg, respectively, compared with 7.3% and 7.4% for empagliflozin 10 mg and 25 mg, respectively, and 7.3% for linagliptin 5 mg. The proportion of patients achieving an HbA1C of less than 7% with empagliflozin/linagliptin 10/5 mg or 25/5 mg was 58% and 62%, respectively, compared with 28%, 33%, and 36% for empagliflozin 10 mg, empagliflozin 25 mg, and linagliptin 5 mg, respectively.

Through 52 weeks of treatment, the overall incidence of hypoglycemia was 2.2% and 3.6% for empagliflozin/linagliptin 10/5 mg and 25/5 mg, respectively. A lower dose of an insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when combined with empagliflozin/linagliptin.

The most common adverse events (AEs) associated with empagliflozin/linagliptin included urinary tract infection, nasopharyngitis, and upper respiratory tract infection. Serious AEs can include pancreatitis, dehydration, vaginal yeast infection, and yeast infection of the penis.

Source: Eli Lilly, February 2, 2015

Lenvima for Thyroid Cancer

Lenvatinib (Lenvima, Eisai Inc) has received FDA approval to treat patients with progressive, differentiated thyroid cancer (DTC) whose disease has progressed despite receiving radioactive iodine therapy.

Lenvatinib is a kinase inhibitor that works by blocking certain proteins from helping cancer cells grow and divide. Its efficacy was demonstrated in 392 patients with progressive, radioactive iodine-refractory DTC who were randomly assigned to receive either lenvatinib or placebo. Median progression-free survival (PFS) with lenvatinib was 18.3 months, compared with 3.6 months for placebo. In addition, 65% of patients treated with lenvatinib demonstrated reductions in tumor size compared with 2% of placebo-treated patients.

The most common adverse effects of lenvatinib included hypertension, fatigue, diarrhea, arthralgia, myalgia, decreased appetite and weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar–plantar erythrodysesthesia syndrome, abdominal pain, and dysphonia. In addition, lenvatinib may cause cardiac failure, arterial thromboembolic events, hepatotoxicity, renal failure and impairment, gastrointestinal perforation or fistula, QT-interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, and serious hemorrhage.

Sources: FDA, February 13, 2015, and New England Journal of Medicine, February 12, 2015

Natpara for Hypocalcemia In Hypoparathyroidism

Parathyroid hormone (Natpara, NPS Pharmaceuticals) has won FDA approval to control hypocalcemia in patients with hypoparathyroidism.

Hypoparathyroidism occurs when the body secretes abnormally low levels of parathyroid hormone, which helps regulate the body’s calcium and phosphorus levels. The disorder results from the loss of function of the parathyroid glands. The FDA granted an orphan drug designation to parathyroid hormone, an injection administered once daily to help regulate calcium levels.

The safety and efficacy of parathyroid hormone were evaluated in a clinical trial designed to determine whether parathyroid hormone could replace or reduce the use of vitamin D or oral calcium; 124 subjects were randomly assigned to active treatment or placebo. Among those treated with parathyroid hormone, 42% achieved normal blood calcium levels on reduced doses of calcium supplements and active forms of vitamin D, compared with 3% of placebo-treated subjects.

A boxed warning notes that osteosarcoma has been observed in animal studies with parathyroid hormone, although it is not known whether this problem may occur in humans. Because of the potential risk, however, the treatment is recommended only for patients whose hypocalcemia cannot be controlled with calcium supplementation and active forms of vitamin D, and for whom the potential benefits of parathyroid hormone are considered to outweigh this potential risk. Parathyroid hormone is available under a risk evaluation and mitigation strategy.

The most common side effects observed with parathyroid hormone treatment have included sensations of tingling, tickling, pricking, or paresthesia; low blood calcium levels; headache; high blood calcium levels; and nausea.

Source: FDA, January 23, 2015

Vaccine for Serogroup B Meningococcal Disease

The FDA has approved Bexsero (Novartis Vaccines and Diagnostics Inc.), a vaccine to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B in individuals 10 through 25 years of age.

N. meningitidis is a leading cause of bacterial meningitis. Before the FDA approved the first meningococcal serogroup B vaccine in October 2014, meningococcal vaccines in the U.S. covered only four of the five main serogroups of N. meningitidis that cause meningococcal disease: A, C, Y, and W. Vaccination is the most effective way to prevent meningococcal disease.

Three studies evaluated the efficacy of Bexsero in approximately 2,600 adolescents and young adults. Among those who received two doses of Bexsero, 62% to 88% had antibodies in their blood after vaccination that killed three N. meningitidis serogroup B strains in laboratory tests, compared with 0% to 23% before vaccination. Bexsero’s safety was assessed in approximately 5,000 participants. The most common adverse effects were injection-site pain and swelling, headache, diarrhea, muscle pain, joint pain, fatigue, and chills.

The FDA evaluated Bexsero through its accelerated approval pathway and awarded the vaccine breakthrough therapy status.

Source: FDA, January 23, 2015

Prestalia for Hypertension

The FDA has approved the first fixed-dose combination of perindopril arginine and amlodipine (Prestalia, Symplmed Pharmaceuticals) for the treatment of hypertension. The medication may be used in patients whose blood pressure is not adequately controlled on monotherapy or as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals.

The FDA’s approval was based on the phase 3 Perindopril Amlodipine for the Treatment of Hypertension (PATH) trial, which included 837 hypertension patients. The fixed-dose combination of perindopril arginine/amlodipine besylate in a single pill was significantly more effective than either compound alone in reducing sitting diastolic and sitting systolic blood pressure after six weeks of treatment.

The findings also suggested that the combination may provide a better risk–benefit ratio than either treatment alone. Other clinical studies have shown that the use of these classes of drugs together may reduce cardiovascular events. Perindopril arginine is an angiotensin-converting enzyme inhibitor and amlodipine is a dihydropyridine calcium-channel blocker.

Source: Symplmed Pharmaceuticals, January 26, 2015

Cosentyx for Psoriasis

Secukinumab (Cosentyx, Novartis) has received FDA approval for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy, phototherapy, or a combination of both.

Secukinumab is the first approved psoriasis medication to bind selectively to interleukin-17A (IL-17A), thereby inhibiting interaction with the IL-17 receptor. The drug is administered via subcutaneous injection.

The agency based its decision on data from 10 phase 2 and 3 trials that examined the efficacy and safety of secukinumab (150 mg and 300 mg) in 3,990 patients with moderate-to-severe plaque psoriasis. Safety and efficacy outcomes met all primary and key secondary endpoints, including the Psoriasis Area and Severity Index (PASI 75 and PASI 90) and the Investigator’s Global Assessment modified 2011 (IGA) 0/1 responses, showing significant skin clearance at week 12.

The protein IL-17A is involved in inflammation. By binding to IL-17A, the antibody secukinumab prevents it from binding to the IL-17 receptor and inhibits its ability to trigger the inflammatory response that plays a role in the development of plaque psoriasis.

Sources: FDA and Novartis, January 21, 2015

Triferic for Iron Replacement

The FDA has approved soluble ferric pyrophosphate (Triferic, Rockwell Medical, Inc.) as an iron-replacement product to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease.

The iron compound is delivered to hemodialysis patients via dialysate, replacing the ongoing iron losses that occur during dialysis. Triferic is introduced into bicarbonate concentrate at the dialysis clinic and is subsequently mixed into dialysate. Once in dialysate, Triferic crosses the dialyzer membrane and enters the blood, where it immediately binds to transferrin and is transported to erythroid precursor cells to be incorporated into hemoglobin.

Delivered with each hemodialysis treatment (three or four times a week), the product can compensate for the estimated 5 to 7 mg of iron loss from ongoing gastrointestinal and hemodialysis-related blood losses that occur in hemodialysis-dependent patients.

Primary efficacy evidence for Triferic was obtained from two placebo-controlled, phase 3 studies in 585 patients who were dialyzed with dialysate containing either Triferic (110 mcg of iron per liter of dialysate) or placebo. The results demonstrated a difference of 0.36 g/dL in favor of Triferic in the mean change in hemoglobin from baseline to the end of treatment at 48 weeks. Triferic’s safety profile was similar to that of placebo.

Sources: Rockwell Medical, January 26, 2015, and FDA briefing document, October 6, 2014

Pazeo for Ocular Allergy Itching

The FDA has approved olopatadine hydrochloride ophthalmic solution 0.7% (Pazeo, Alcon) to treat ocular itching associated with allergic conjunctivitis. The daily dose is one drop.

Results from two clinical studies showed that olopatadine hydrochloride ophthalmic solution 0.7% significantly improved relief of ocular itching associated with allergic conjunctivitis at 24 hours post-treatment compared with olopatadine solution 0.2% (Pataday, Alcon). The safety profile of olopatadine 0.7% solution was comparable with that of olopatadine 0.2%. In the studies, the most common adverse events included blurred vision, dry eye, superficial punctate keratitis, dysgeusia, and abnormal sensations in the eye.

Source: Alcon, February 2, 2015

Evotaz for HIV

The FDA has approved atazanavir/cobicistat (Evotaz, Bristol-Myers Squibb), a fixed-dose, once-daily pill for the treatment of human immunodeficiency virus (HIV) infection that combines a protease inhibitor with a pharmacokinetic enhancer.

Atazanavir/cobicistat 300/150 mg was approved in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. The medications are also marketed separately, atazanavir as Reyataz (Bristol-Myers Squibb) in 200-mg and 300-mg capsules and cobicistat as Tybost (Gilead Sciences).

In a randomized, double-blind clinical study involving 692 treatment-naïve adults, the efficacy and safety of atazanavir 300 mg with cobicistat 150 mg were compared with that of atazanavir 300 mg with ritonavir 100 mg in combination with emtricitabine/tenofovir disoproxil fumarate (TDF). Participants had a mean baseline plasma HIV-1 RNA of 4.8 log10 copies/mL, and a mean baseline CD4+ cell count of 352 cells/mm3.

At 48 weeks, 85% of patients in the atazanavir/cobicistat arm achieved HIV-1 RNA levels of less than 50 copies/mL compared with 87% of patients in the atazanavir/ritonavir arm. Virological failure (HIV-1 RNA of 50 copies/mL or more) was 6% in the atazanavir/cobicistat arm and 4% of the atazanavir/ritonavir arm. No protease inhibitor resistance was detected through 48 weeks of treatment.

Source: Bristol-Myers Squibb, January 29, 2015

Prezcobix for HIV

Darunavir/cobicistat (Prezcobix, Johnson & Johnson), a once-daily, fixed-dose tablet that combines a protease inhibitor with a cytochrome P450 3A4 inhibitor, has won FDA approval for the treatment of human immunodeficiency virus (HIV) infection.

Darunavir/cobicistat 800/150 mg is indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents in treatment-naïve and treatment-experienced adults with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, or L89V). Darunavir is marketed as Prezista (Johnson & Johnson) and cobicistat as Tybost (Gilead Sciences).

FDA approval was based on bioequivalence data from the use of a darunavir and cobicistat fixed-dose combination tablet compared with single agents and on the results of a clinical study evaluating the safety and efficacy of cobicistat-boosted darunavir for the treatment of HIV-1 in adults with no darunavir resistance-associated mutations.

The efficacy of darunavir/cobicistat 800/150 mg is based on findings from clinical trials of darunavir coadministered with ritonavir and from pharmacokinetic trials showing similar exposures of darunavir when boosted with cobicistat compared with darunavir boosted with ritonavir.

Source: Johnson & Johnson, January 29, 2015

Lamivudine/Raltegravir for HIV

The FDA has approved lamivudine/raltegravir (Dutrebis, Merck Pharmaceuticals), a fixed-dose combination tablet for use in combination with other antiretroviral products for the treatment of human immunodeficiency virus (HIV) in patients who are at least 6 years of age and weigh at least 30 kg.

The recommended dosage is one tablet of lamivudine/raltegravir 150/300 mg, taken twice daily with or without food by HIV-1 patients, but the FDA says Merck does not expect to make Dutrebis commercially available in the U.S. at this time.

The approval was based on an open-label, single-dose, randomized, two-period crossover study in 108 healthy subjects. One lamivudine/raltegravir fixed-dose combination tablet was shown to provide lamivudine and raltegravir exposures comparable to one 150-mg tablet of lamivudine (Epivir, ViiV Healthcare) and one 400-mg tablet of raltegravir (Isentress, Merck). Due to the higher bioavailability of raltegravir in Dutrebis, the exposures provided by the 300-mg dose of raltegravir are comparable to the 400 mg of raltegravir in Isentress.

Clinical trials have not been performed with the lamivudine/raltegravir combination tablet. The indication of Dutrebis is based on efficacy and safety data demonstrated in clinical trials with lamivudine and with raltegravir.

Source: FDA, February 6, 2015

Generic Approvals

Esomeprazole Magnesium Delayed-Release Capsules

The FDA has approved the first generic esomeprazole magnesium delayed-release capsules, used to treat gastroesophageal reflux disease in adults and children ages 1 and older. The brand-name product, Nexium Delayed-Release Capsules (AstraZeneca), had annual U.S. sales of approximately $6 billion as of November 2014, according to IMS data.

Ivax Pharmaceuticals, Inc., a subsidiary of Teva Pharmaceuticals USA, gained approval to market esomeprazole in 20-mg and 40-mg capsules. Esomeprazole is a proton pump inhibitor (PPI) that reduces the amount of acid in the stomach.

Esomeprazole capsules are also approved to reduce the risk of gastric ulcers associated with use of nonsteroidal anti-inflammatory drugs, to treat the stomach infection Helicobacter pylori along with certain antibiotics, and to treat conditions where the stomach makes too much acid, including Zollinger-Ellison syndrome.

Generic esomeprazole capsules will be dispensed with a patient medication guide that provides important information about the medication’s use and risks. The most serious risks are gastrointestinal problems, including severe diarrhea, and a warning that people who take multiple daily doses of PPIs for a long time may have an increased risk of bone fractures.

The most common side effects reported by those taking Nexium in clinical trials include headache, diarrhea, nausea, flatulence, abdominal pain, sleepiness, constipation, and dry mouth.

Sources: FDA and Teva Pharmaceutical Industries Ltd., January 26, 2015

Ritonavir Tablets

The FDA has approved ritonavir tablets, USP, 100 mg (Roxane Laboratories), the first generic version of Norvir (AbbVie). Ritonavir is a human immunodeficiency virus (HIV) protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Ritonavir carries a boxed warning noting that coadministration with several classes of drugs, including sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations, may result in potentially serious and/or life-threatening adverse events due to ritonavir’s possible effects on their hepatic metabolism.

Sources: FDA, January 15, 2015, and Norvir prescribing information

Lamotrigine ODT

Impax Laboratories, Inc., has received FDA approval for orally disintegrating 25-, 50-, 100-, and 200-mg tablets of lamotrigine in blister packaging—the first generic version of GlaxoSmithKline’s Lamictal ODT, which is indicated for the treatment of epilepsy and bipolar disorder.

Source: Impax Laboratories, Inc., January 26, 2015


Imbruvica for Waldenström’s Macroglobulinemia

Ibrutinib (Imbruvica, Janssen Biotech/Pharmacyclics, Inc.) has become the first FDA-approved therapy specifically indicated for Waldenström’s macroglobulinemia (WM), a rare, indolent type of B-cell lymphoma.

The new indication is based on data from a multicenter Dana-Farber Cancer Institute phase 2 study that evaluated the efficacy and tolerability of ibrutinib 420 mg once daily in 63 patients with previously treated WM (median age, 63 years). Nearly 51% achieved a partial response (PR), and 11% achieved a very good PR; no complete responses were reported. The median time to response was 1.2 months and the median duration of response has not been reached (range, more than 2.8 to more than 18.8 months).

Neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue were the most common adverse events, which led to discontinuation in 6% of patients and dose reductions in 11% of patients.

Ibrutinib blocks Bruton’s tyrosine kinase, a protein that transmits important signals to B cells and that is needed by specific cancer cells to multiply and metastasize. Ibrutinib is also indicated to treat some patients with mantle cell lymphoma and chronic lymphocytic leukemia.

Source: Janssen Biotech, January 29, 2015

Lucentis for More Cases Of Diabetic Retinopathy

The FDA has expanded the use for ranibizumab injection, 0.3 mg (Lucentis, Genentech) to treat diabetic retinopathy in patients with diabetic macular edema (DME). Lucentis, injected into the eye by a physician once a month, is meant to be used with appropriate interventions to control blood sugar, blood pressure, and cholesterol.

The drug’s safety and efficacy to treat diabetic retinopathy (DR) with DME were established in two clinical studies involving 759 participants who were followed for three years. Participants being treated with Lucentis showed significant improvement in the severity of their DR at two years compared with patients who did not receive an injection.

The most common side effects include bleeding of the conjunctiva, eye pain, floaters, and increased intraocular pressure. Serious side effects include endophthalmitis and retinal detachments.

The FDA granted Lucentis for DR with DME a breakthrough therapy designation and approved the new use under the priority review program. The agency previously approved Lucentis to treat DME and macular edema secondary to retinal vein occlusions. Lucentis is also approved to treat neovascular age-related macular degeneration.

Source: FDA, February 6, 2015

Revlimid Use Expanded For Multiple Myeloma

The FDA has expanded the indication for lenalidomide (Revlimid, Celgene Corporation) in combination with dexamethasone to include patients newly diagnosed with multiple myeloma. Lenalidomide plus dexamethasone was approved in 2006 for use in multiple myeloma patients who had received at least one prior therapy.

The new approval was based on phase 3 studies that evaluated continuous lenalidomide in combination with dexamethasone (continuous Rd) until disease progression compared with melphalan, prednisone, and thalidomide (MPT) for 18 months as the primary analysis, and a fixed duration of 18 cycles of lenalidomide/dexamethasone (Rd18) as a secondary analysis. The study involved 1,623 newly diagnosed patients who were not candidates for stem-cell transplant.

Median progression-free survival was significantly longer for patients receiving continuous Rd than for those treated with MPT (25.5 months versus 21.2 months, respectively). Median overall survival in the two groups was 58.9 months and 48.5 months, respectively. Patients in the continuous Rd arm showed a 25% reduction in the risk of death compared with those in the MPT arm. Common adverse events in the continuous Rd and Rd18 arms included diarrhea, anemia, neutropenia, fatigue, back pain, insomnia, asthenia, rash, decreased appetite, cough, pyrexia, muscle spasms, and abdominal pain.

Source: Celgene; February 18, 2015

Vyvanse for Binge Eating

Lisdexamfetamine dimesylate (Vyvanse, Shire U.S., Inc.) has become the first medication approved by the FDA to treat binge-eating disorder (BED) in adults.

BED patients have recurrent episodes of compulsive overeating during which they consume larger amounts of food than normal and experience the sense that they lack control. Patients eat when they are not hungry, often to the point of being uncomfortably full. BED may lead to shame, embarrassment, and weight gain.

The efficacy of lisdexamfetamine was demonstrated in two clinical studies that included 724 adults with moderate-to-severe BED. Participants taking lisdexamfetamine experienced a decrease in the number of binge-eating days per week and had fewer obsessive-compulsive binge-eating behaviors compared with those receiving placebo.

The most serious risks of lisdexamfetamine include psychiatric problems and heart complications, including sudden death in people who have heart problems or heart defects, and stroke and heart attack in adults. Central nervous system stimulants, including lisdexamfetamine, may cause psychotic or manic symptoms, such as hallucinations, delusional thinking, or mania, even in individuals with no history of psychotic illness. The most common lisdexamfetamine side effects in clinical trials included dry mouth, insomnia, increased heart rate, jittery feelings, constipation, and anxiety.

Lisdexamfetamine was approved in 2007 for once-daily treatment of attention-deficit hyperactivity disorder in patients 6 years of age and older. It is a Schedule II controlled substance because it has a high potential for abuse. This new indication received the FDA’s priority review.

Source: FDA, January 30, 2015


Abuse-Deterrent Zohydro ER

The FDA has approved a new formulation for hydrocodone bitartrate extended-release capsules (Zohydro ER, Zogenix, Inc.) designed to provide abuse-deterrent properties without changing the release properties of hydrocodone when the drug is used as intended. The product incorporates BeadTek technology that immediately forms a viscous gel when crushed and dissolved in liquids or solvents.

To support an amended label, Zogenix will provide the FDA with data from ongoing human abuse liability studies that will characterize the abuse-deterrent properties of the new formulation, which maintains the efficacy and pharmacokinetic profile of the original. All prescribed strengths, ranging from 10 mg to 50 mg, are being shifted to the new formulation without disruption to patients.

Zohydro ER is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. It does not contain acetaminophen, reducing the risk for liver toxicity. The product carries a boxed warning on the risks of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; interaction with alcohol; and cytochrome P450 3A4 interaction.

Source: Zogenix, Inc., January 30, 2015


Breakthrough Therapy

Obeticholic Acid for NASH

The FDA has awarded breakthrough therapy status to the investigational product obeticholic acid (Intercept Pharmaceuticals, Inc.) for the treatment of patients with nonalcoholic steatohepatitis (NASH) with liver fibrosis.

Obeticholic acid (OCA) is a bile acid analog and first-in-class agonist of the farnesoid X receptor. It is being developed for the treatment of several chronic liver diseases, including NASH, primary biliary cirrhosis, and primary sclerosing cholangitis. Two placebo-controlled, phase 2 clinical trials have assessed its effects—one on insulin sensitivity in patients with nonalcoholic fatty liver disease, and one on liver histology and fibrosis in NASH patients.

Source: Intercept Pharmaceuticals, Inc., January 29, 2015

Priority Review Status

Praluent for Cholesterol Control

The FDA is giving priority review to alirocumab (Praluent, Regeneron Pharmaceuticals/Sanofi) for the treatment of patients with hypercholesterolemia. Under the Prescription Drug User Fee Act, the target action date is July 24, 2015.

Alirocumab is an investigational monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). It is administered via subcutaneous injection. By inhibiting PCSK9, a determinant of circulating low-density lipoproteincholesterol (LDL-C) levels in the blood, alirocumab has been shown in preclinical studies to increase the number of LDL receptors on hepatocytes, thereby lowering LDL-C levels. The biologics license application for alirocumab contains data from more than 5,000 patients, including 10 phase 3 ODYSSEY trials.

Source: Regeneron Pharmaceuticals, January 26, 2015

Three-Month Paliperidone Palmitate

The FDA has granted priority review status to a three-month formulation of the atypical antipsychotic drug paliperidone palmitate (Janssen) to treat schizophrenia in adults. If approved, it would be the first long-acting atypical antipsychotic with a dosing schedule of just four times a year.

A phase 3, randomized, double-blind study of more than 500 patients evaluated the efficacy of three-month paliperidone palmitate compared with that of placebo in delaying the first occurrence of relapse symptoms of schizophrenia. Patients who were randomly assigned to treatment were stabilized with Invega Sustenna (once-monthly paliperidone palmitate, Janssen) before receiving the investigational three-month formulation.

The study was stopped early for efficacy after an interim review by an independent data-monitoring committee found that active treatment achieved a statistically significant difference from placebo in delaying the time to relapse. Based on this study, the safety profile of the paliperidone palmitate three-month formulation is consistent with that of once-monthly Invega Sustenna.

Source: Janssen, January 19, 2015

Yondelis for Soft Tissue Sarcoma

Trabectedin (Yondelis, Janssen) will receive the FDA’s priority review for the treatment of patients with advanced soft tissue sarcoma, including liposarcoma and leiomyosarcoma, who have undergone prior chemotherapy including an anthracycline.

The filing is based on the phase 3, randomized, open-label study ET743-SAR-3007, which is evaluating the safety and efficacy of trabectedin versus dacarbazine for the treatment of patients with advanced liposarcoma and leiomyosarcoma in more than 500 patients. Trabectedin—a novel, multimodal, synthetically produced antitumor agent originally derived from the sea squirt, Ecteinascidia turbinate—prevents tumor cells from multiplying.

Source: Janssen, February 3, 2015

Orphan Drug Designations

Reovirus for Ovarian Cancer

The FDA has granted an orphan drug designation to Reolysin (Oncolytics Biotech Inc.) for the treatment of ovarian cancer. Reolysin is a proprietary variant of the common, nonpathogenic reovirus (or “respiratory enteric orphan virus”).

Two studies have assessed Reolysin in the treatment of ovarian cancer. The first, a phase 1/2 clinical trial involving patients with metastatic ovarian, peritoneal, or fallopian-tube cancer treated with concurrent intravenous and intraperitoneal Reolysin, provided evidence of viral targeting of, and replication in, peritoneal and ovarian cancer cells. The second is an ongoing, randomized phase 2 trial of weekly paclitaxel and Reolysin compared with weekly paclitaxel alone in patients with persistent or recurrent ovarian, fallopian-tube, or primary peritoneal cancer.

Source: Oncolytics Biotech Inc., February 11, 2015

AIT-CF for Cystic Fibrosis

AIT-CF (Advanced Inhalation Therapies Ltd.) has received as FDA orphan drug designation for adjunctive treatment of cystic fibrosis (CF).

AIT-CF is a nitric oxide (NO) formulation and delivery system designed to carry a high dose to the lungs using positive air pressure and integrated monitoring parameters. The system has the potential to eliminate microbial infections, the primary complication of CF.

The body produces NO naturally as an antimicrobial defense mechanism, but to date no system has been able to deliver an effective, nontoxic antimicrobial dosage to the lungs. AIT’s system continuously monitors safety and efficacy parameters. A phase 2, open-label, multicenter study demonstrated the product’s safety and efficacy, the company said.

Source: Advanced Inhalation Therapies Ltd., February 9, 2015

Fast-Track Designations

SHP609 for Hunter Syndrome

The FDA has granted a fast-track designation to idursulfase-IT (SHP609, Shire PLC) for the treatment of neuro-cognitive decline associated with Hunter syndrome (mucopolysaccharidosis II). This investigational formulation of idursulfase, designed for direct administration into the cerebrospinal fluid via an intrathecal drug delivery device, is being developed for use with Shire’s approved treatment for Hunter syndrome, idursulfase (Elaprase).

Shire is enrolling patients in a phase 2/3, pivotal, controlled, randomized, open-label, multicenter, assessor-blinded trial designed to determine the effect on clinical parameters of neurodevelopmental status of monthly administration of idursulfase IT in pediatric patients with Hunter syndrome and early cognitive impairment who already receive and tolerate Elaprase. An extension study is planned to assess long-term safety and efficacy.

Source: Shire PLC, January 26, 2015

Neutrolin for Catheter Safety

The FDA has granted a fast-track designation to Neutrolin Catheter Lock Solution (CorMedix Inc.), a formulation of taurolidine, citrate, and heparin that decreases the catheter threats of infection, thrombosis, and biofilm. The agency also designated Neutrolin a qualified infectious disease product for oncology, hemodialysis, and intensive care unit patients, whose lives can be threatened by catheter-related bloodstream infections and clotting.

Neutrolin has shown antimicrobial activity against many of the pathogens known to cause bloodstream infections in these patients, and CorMedix intends to conduct clinical trials in this population.

Sources: CorMedix Inc., January 15, 2015, and January 29, 2015

New Dosing Option for Hizentra

The FDA has expanded the administration options for immune globulin subcutaneous (human), 20% liquid (Hizentra, CSL Behring) to include the ability to individualize therapy with flexible dosing—treatment at regular intervals from daily to once every two weeks—for people with primary immunodeficiency (PI).

Hizentra received FDA approval in March 2010 as a once-weekly therapy to help protect people with PI against infections and was approved for dosing once every two weeks in September 2013. FDA approval of flexible dosing is based on pharmacometrics (modeling and simulation). Clinical trials using these alternative dosing regimens were not conducted.

Source: CSL Behring, February 2, 2015

Medication Recall

Hospira Ketorolac Tromethamine Injection

Hospira, Inc., is recalling 63 lots of ketorolac tromethamine injection, USP, after confirming a report of visible, floating particulate—identified as calcium-ketorolac crystals—in glass flip-top vials.

The lots were distributed from February 2013 to December 2014 in the United States and from January 2014 to July 2014 in Singapore. A list of lot numbers is available at For assistance, call Stericycle at 1-888-345-4680, Monday through Friday, 8 a.m. to 5 p.m. Eastern time.

Source: Hospira, Inc., February 10, 2015


Tapentadol PR Manages Pain

Prolonged-release tapentadol (Nucynta ER, Janssen) performs well compared with classic opioid analgesics in treating severe, chronic pain—especially in terms of tolerability and efficacy, according to a team of Spanish and German researchers.

A single analgesic often cannot address mixed or neuropathic chronic pain because different pain mechanisms are at work. However, combination therapy (an opioid analgesic and a coanalgesic) may increase the risk of adverse effects and cause patients to abandon treatment.

Tapentadol belongs to a proposed new class of centrally acting analgesics with two mechanisms of action: μ-opioid receptor agonism and noradrenaline reuptake inhibition. That may make tapentadol easier to use and ultimately more effective than classic opioid analgesics.

After reviewing the literature and unpublished data, the researchers summarized key points about tapentadol prolonged-release (PR). Its lower rates of nausea, vomiting, dizziness, and constipation compared with classic opioid analgesics mean the drug can be titrated up more quickly for pain relief, with higher possible doses (up to 500 mg per day). The recommended dose range is sufficient to control severe-to-very-severe pain. Because of its tolerability, when switching patients from opioids, it may be possible to titrate tapentadol PR to doses above the equivalent analgesic dose of previously used opioids.

Fewer adverse effects early in therapy and in long-term use may improve adherence and quality of life, the researchers say. Although withdrawal symptoms are common when switching opioids, rates of withdrawal were “notably lower” when switching from an opioid to tapentadol PR. Even abrupt withdrawal from tapentadol PR seems to produce only mild-to-moderate symptoms, if any.

In studies comparing tapentadol PR with placebo and controlled-release oxycodone in patients with moderate-to-severe chronic pain, tapentadol PR showed non-inferior or superior efficacy, as well as significantly greater improvements from baseline for measures of health-related quality of life. Tapentadol PR also has a low potential for drug–drug interactions.

Tapentadol PR is well tolerated and effective during up to two years of treatment in patients with chronic pain, with no acquired tolerance to the analgesic effects over time and a low level of abuse.

Source: Clinical Therapeutics, January 2015

Lessons From ARISTOTLE

An increase in strokes when apixaban (Eliquis, Bristol-Myers Squibb) was discontinued at the end of the ARISTOTLE trial may have been related to the transition to the vitamin K antagonist (VKA), a study led by Duke University Medical Center suggests.

The risk of bleeding and/or thromboembolism can increase in the interval between stopping one oral anticoagulant and starting a different one. In ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), 6,809 patients were taking apixaban and 6,588 were on warfarin. Patients who completed the trial had a two-day bridging period with apixaban or placebo (if they were taking warfarin) while beginning VKA therapy.

After a 30-day follow-up, 21 strokes or systemic emboli and 26 major bleeding events were reported in the apixaban group, compared with five strokes or systemic emboli and 10 major bleeding events in the warfarin group. When the analysis was restricted to the 84% who completed treatment and received VKA therapy, the pattern of events was similar (14 strokes with apixaban versus two with warfarin). After adjusting for major predictors of the primary efficacy and safety outcomes, the results were again similar: Stroke or systemic embolism increased more than fourfold and major bleeding more than doubled in the apixaban group.

The lack of observed excess risk in the apixaban group when the study drug was prematurely discontinued supports the idea that VKA is implicated, the researchers say. At the start of the trial, they observed, warfarin-naïve patients had a higher risk of events in the first 30 days than patients who were continuing warfarin. Thus, they suggest, there may be a period of higher hazard early after VKA therapy is initiated. Stopping anticoagulation could raise the risk by allowing underlying thrombosis to occur or because of a transient rebound hypercoagulable state.

Or, they add, there could be an increased risk related to initiation of the other anticoagulant. The “only plausible explanation” for the higher rate of bleeding and stroke, they propose, is the VKA therapy—where uncertainty of dose, variability in anticoagulation intensity, and delayed onset and offset of effect all could play a part.

The researchers suggest that a transition from a novel agent to warfarin should be avoided when possible by continuing the novel agent. When transition is necessary, they advise taking special care during this “very high-risk period.”

Source: American Heart Journal, January 2015

Polypharmacy in Cancer Patients

Patients with advanced cancer face risks from polypharmacy, researchers found after analyzing medication use in 2,282 oncology patients. Those patients need drugs for multiple symptoms, including severe pain, and may receive drugs for multiple diseases and from multiple physicians.

The Polish and Norwegian researchers analyzed data from 17 cancer and palliative care centers in the European Pharmacogenetic Opioid Study. Patients received as many as 20 drugs, with a mean of eight. More than 28% of patients used 10 or more drugs. The drugs coadministered most often were proton pump inhibitors, laxatives, corticosteroids, acetaminophen, nonsteroidal anti-inflammatories, metoclopramide, benzodiazepines, anticoagulants, antibiotics, anticonvulsants, diuretics, and antidepressants. Two opioids were given concomitantly to 163 patients.

Drug–drug interactions were common. About 45% of patients received at least one unnecessary drug, including lipid-lowering drugs, hormone replacement therapy, vitamins, and minerals. About 33% were given potentially unnecessary drugs, including anticancer drugs, megestrol acetate, drugs for cardiovascular indications, gastroprotective agents, and allopurinol. About 6% were given duplicate or antagonizing drugs, such as two benzodiazepines or an angiotensin-converting enzyme inhibitor plus an angiotensin-receptor blocker.

Drug–drug interactions raised the risk of sedation, gastric ulcerations, bleeding, and neuropsychiatric and cardiac complications. For example, 48% of the patients received at least one drug, in addition to opioids, with a potential to induce or aggravate drowsiness.

More than half of the patients were exposed to drugs that exert and often share affinity for dopamine, serotonin, and muscarinic receptors, the researchers say, which increases the risk of neuropsychiatric complications. The researchers found that 418 patients (18%) used drugs with a risk of torsades de pointes.

Many patients were exposed to clinically relevant drug–drug interactions involving cytochrome P450 3A4, the researchers say. When drugs influencing CYP3A4 activity are introduced or stopped, opioid metabolism can change rapidly, making overdoses possible.

Older patients, patients with lower performance status scores, and patients treated in oncology wards or palliative care units/hospices received more medications—so the most vulnerable patients had the highest risk of drug–drug interactions.

Source: Journal of Pain and Symptom Management, December 2014

Photo Opportunities

With the constant coming and going of physicians, nurses, and other staff, hospital patients sometimes have trouble remembering who’s who and what they’re there to do. Studies show that memory aids, such as names written on dry-erase boards in patient rooms, can help. University of Toronto researchers suggest that adding photos can do even more.

The researchers assigned patients to one of three groups. A control group (A) received no intervention; group B received a handout with the names and roles of each staff member; and group C received handouts with names, roles, and photographs.

The researchers later surveyed the patients to learn whether they remembered their clinicians and their roles. Of the 186 patients who completed the survey, 30% could not initially recall a single clinician by name without being shown visual cues. Most patients found the names somewhat or very useful (87%), but more found the addition of photos somewhat or very useful (92%).

The number of clinicians the patients recognized was relatively low. But the handouts helped patients recall, on average, two or three clinicians from teams usually consisting of five or more members. Patients in group B correctly identified significantly more clinician names than patients in group A. Group C patients, who also received photographs, correctly identified one more clinician than those in group B and recalled, on average, one more name and two more faces than patients in group A.

The questionnaires also assessed patients’ perception of communication quality. In all groups, most patients (84% to 86%) felt their care team members listened and explained well.

The researchers note that helping patients be more familiar with their care team has the potential to reduce uncertainty and anxiety.

Source: American Journal of Medicine, January 2015

Post-AMI Ischemic Strokes Fall

Ischemic stroke after acute myocardial infarction (AMI) is on the decline, according to a study by researchers from Yale University, Harvard University, and other institutions. Between 1999 and 2010, rates fell 24%—one less subsequent stroke for every 125 AMI hospitalizations.

The researchers analyzed data on Medicare beneficiaries for 57,848 hospitalizations for ischemic stroke and 4,412 hospitalizations for hemorrhagic stroke within one year of AMI. The one-year rate of ischemic stroke decreased from 3.4% to 2.6%, with a risk-adjusted annual decline of 3% across all age, sex, and race subgroups. The 30-day mortality for patients with ischemic stroke dropped from 20% to 18%, and one-year mortality dropped from 38% to 35%.

Hemorrhagic stroke remained rare, with rates stable at 0.2%. Mortality rates declined from 48% to 46% at 30 days and from 67% to 61% at one year.

The decline in ischemic stroke may be due to improved treatment, the researchers note. During the study period, more patients were being treated with procedures and antithrombotic therapies in the acute setting as well as secondary prevention strategies, such as statins and antihypertensive medications, and more patients were prescribed dual antiplatelet therapy. However, the researchers could not establish a direct association between the lower rates of stroke and improvements in AMI care.

The downward slope may also reflect nationwide efforts to reduce risk with lifestyle changes, such as smoking cessation. Preventive strategies may have started having the most noticeable effects in the early 2000s. The researchers say the observed decline in the rate of ischemic stroke appeared to plateau after 2006.

Source: American Heart Journal, January 2015

How Falls and Obesity Relate

About one-third of older adults fall, many of them more than once. But fear of falling again may lead them to stop being physically active, which in turn can cause them to put on extra weight. And those factors, individually and combined, may contribute to further falls, according to researchers from the University of New South Wales in Australia.

The researchers examined the extent to which the association between obesity and falls is mediated by related factors, such as chronic disease, sedentary behavior, mood, pain, and medication use. They used data from the 2009 New South Wales Fall Prevention Baseline Survey of 5,681 adults over the age of 65 years living in the community. The respondents were asked whether they had fallen (lost their balance, tripped, or slipped) in the last 12 months. They also answered questions about their knowledge and perception of falls and their physical activity. The information included weight, comorbidities, and medication use.

Roughly 20% of the respondents were obese. Compared with nonobese individuals, they had a significantly higher proportion of falls, diabetes, arthritis, heart disease/angina, high blood pressure, moderate-to-extreme pain or discomfort, and moderate-to-extreme anxiety or depression. They were also more likely to be using four or more medications, including tranquilizers, antidepressants, and blood thinners. The obese adults were much less active; significantly fewer had walked two or more hours in the week before the survey, and significantly more had sat for more than eight hours a day on weekdays.

When all weight groups were compared, obesity was associated with a 25% higher risk of having fallen in the previous 12 months. It also increased the relative risk of a fall for each mediator. Of the potential mediating factors, all were significantly associated with obesity, except for osteoporosis, stroke, cataracts, and tranquilizers. The researchers note that stroke, cataracts, and tranquilizers—all commonly linked to falls in older people—may not have been strong factors in this study because they aren’t necessarily more of a risk for obese older adults.

The strongest mediators of the association between obesity and falls were use of sleeping tablets or antidepressants; sitting for more than eight hours a day on weekdays; and having heart disease/angina, moderate or extreme anxiety or depression, or diabetes. After multivariate analysis, the mediators that remained significant were arthritis, problems doing usual activities, use of antidepressants, being sedentary, and having moderate/extreme anxiety or depression.

Source: Archives of Gerontology and Geriatrics, January–February 2015

Cost of Having Diabetes Doubles

The cost of managing diabetes has more than doubled in the past 20 years, according to a study in Diabetes Care. The average diabetes patient spends $2,790 more per year than he or she did in 1987—and more than half of the additional spending is for medications.

Dr. Xiao-hui Zhou, a health economist at the Centers for Disease Control and Prevention, and colleagues compared National Medical Expenditure Survey data from 1987, 2000–2001, and 2010–2011. The 1987 survey, involving 22,538 people, showed that people with diabetes spent $2,588 per person more on health care than people without diabetes. In 2000 and 2010, with approximately 39,000 people responding each time, the extra spending by diabetes patients rose to $4,205 and $5,378, respectively.

When the researchers accounted for factors such as age, race, obesity, and the type of care, 55% of the increased spending was on prescription medications; 24% was for inpatient visits; 15% was for outpatient visits; and 6% went toward emergency department visits and other expenses. Diabetes patients now use more medications and the costs of the drugs have risen.

Dr. Zhou noted that new drugs and devices are constantly emerging and that “patients now receive a more complicated treatment regimen than in the past.” Some newer drugs are eight to 10 times more expensive than older drugs, he said.

Sources: Reuters, February 2, 2015, and Diabetes Care, January 15, 2015


First Tissue Adhesive Approved for Internal Use

The FDA has given the go-ahead to TissuGlu (Cohera Medical, Inc.), the first tissue adhesive approved for internal use.

Surgeons can use the urethane-based adhesive to connect tissue flaps made during surgery to remove excess fat and skin or to restore weakened or separated abdominal muscles (abdominoplasty). Connecting the tissue flaps with an internal adhesive may reduce or eliminate the need for postoperative surgical draining of fluid between the abdominoplasty tissue flaps.

The surgeon uses a hand-held applicator to apply drops of liquid TissuGlu and then positions the abdominoplasty flap in place. Water in the patient’s tissue starts a chemical reaction that bonds the flaps together. The surgeon then proceeds with standard closure of the skin using sutures.

The FDA’s review of TissuGlu included data from a clinical study of 130 participants undergoing elective abdominoplasty. Half received surgical drains and half received TissuGlu without drains. In the study, 73% of the participants who received TissuGlu required no postoperative interventions to drain fluid that had accumulated between the abdominoplasty tissue flaps. In the 27% of patients who required invasive treatments, 21% received needle aspirations alone and 6% received needle aspirations and drains for persistent seroma formation.

Participants who received TissuGlu without surgical drains were generally able to return to most daily activities—such as showering and climbing stairs—sooner than those who had surgical drains. There was no difference between the groups in reported levels of pain or discomfort from the surgery.

Source: FDA, February 4, 2015

ENROUTE Transcarotid Neuroprotection System

The FDA has approved marketing of the ENROUTE Transcarotid Neuroprotection System (Silk Road Medical) for use during a minimally invasive procedure to restore normal blood flow to narrowed carotid arteries. It is the first device designed to access the carotid arteries through an incision in the neck, rather than the groin, and uses a blood flow reversal system to capture pieces of the blockage dislodged during the procedure.

A severe narrowing or blockage of the carotid artery may require a balloon angioplasty procedure in which a balloon on a long catheter is threaded through a patient’s vasculature from the groin to the site of the blockage. The balloon is inflated to open the artery and a stent is placed at the site to keep the artery open. The ENROUTE device allows physicians to insert a catheter into the artery in the neck above the narrowed or blocked section of the artery.

During the stenting procedure, physicians typically use a filter or additional balloon to capture and remove small pieces of debris that might be dislodged and potentially travel to the brain. The ENROUTE device captures debris by temporarily shunting blood flowing through the narrowed section of the artery away from the brain and into a filtering system outside the body. Blood is returned to the body though a vein in the leg. Because the carotid artery branches into many interconnected smaller arteries, the brain still receives oxygenated blood during the procedure.

A clinical trial sponsored by the manufacturer showed that the rate of stroke, heart attack, and death among the ENROUTE patients was 3.5%, significantly lower than the study performance goal of 11%. At least one serious adverse event occurred in 14.2% of patients, including excessive bleeding or injury at the device access site, low blood pressure due to the device or procedure, and blood clot formation within the placed stent. These events are consistent with the type and rate of serious adverse events associated with other carotid artery procedures.

Source: FDA, February 9, 2015

Impella RP Heart Pump

The Impella RP (Right Percutaneous) System has received FDA approval under a humanitarian device exemption.

The system—the first agency-approved percutaneous single-access heart pump designed for right heart support—was submitted for FDA review in September 2014 after the completion of the pivotal RECOVER RIGHT trial.

Delivered through a catheter in the leg, the Impella RP system is indicated for providing circulatory assistance for up to 14 days in pediatric or adult patients who develop acute right heart failure or decompensation after the implantation of a left ventricular assist device, myocardial infarction, heart transplant, or open-heart surgery. Impella RP is designed to provide the flow and pressure needed to compensate for right heart failure. The system does not require a surgical procedure for insertion, and it provides up to 4 L per minute of hemodynamic support.

The FDA is requiring the system’s developer (Abiomed, Inc.) to conduct two post-approval studies. One will include 30 adults, and the other will involve up to 15 pediatric patients with right ventricular failure (RVF). These single-arm, multicenter trials will monitor the post-market safety and probable benefit of the Impella RP device in patients 30 and 180 days after device explant.

The RECOVER RIGHT trial—a prospective, single-arm study—evaluated the safety and probable benefit of the Impella RP device in 30 patients with RVF that was refractory to medical treatment and was deemed to require hemodynamic support. Overall, the survival rate was 73% in the entire population at 30 days.

Source: Abiomed, January 27, 2015

Koning Breast CT System

The FDA has approved marketing of the Koning Breast CT system (Koning Corporation), which can produce 3D images to aid in the diagnosis of breast cancer without compressing the breast.

The patient lies face down on a table that is mounted above the Koning Breast CT (KBCT) hardware. The table has an opening to allow one breast to hang through it. In less than 10 seconds, the KBCT hardware rotates around the breast without compressing it. The system acquires computed tomography data that is used by the software to reconstruct cross-sectional 3D images of the entire breast.

The KBCT is intended for breast cancer diagnosis in women who have suspicious signs or symptoms of breast cancer, or who have abnormal imaging findings and need more imaging tests to determine whether a biopsy should be performed. KBCT images should be read by a physician along with standard screening mammograms. The KBCT is not intended for breast cancer screening.

Source: FDA, January 14, 2015

Some Bone Graft Substitutes May Harm Younger Patients

The use of bone graft substitutes that contain recombinant proteins or synthetic peptides in patients under the age of 18 years has led to serious injuries such as excess bone growth, fluid accumulation, inhibited bone healing, and swelling, the FDA warns.

While such events are also seen in patients over the age of 18, they are of special concern in younger patients because of their smaller size and because their bones are still growing. Any product that affects bone growth could potentially harm skeletal development by altering normal bone formation and growth, especially if implanted near open growth plates.

The FDA considers bone graft substitutes containing recombinant proteins or synthetic peptides to be high-risk (class III) medical devices. The FDA has not evaluated their safety and effectiveness in patients under age 18, and they are not approved for use in this population.

Health care providers should consider alternatives, such as autograft bone, allograft bone, and bone graft substitutes that do not contain recombinant proteins or synthetic peptides, before using bone graft substitutes containing recombinant proteins and synthetic peptides in patients younger than 18 years of age, the FDA says. If the use of such a product is considered the best or only option, providers should inform parents or guardians and patients about the risks and benefits. Providers should closely monitor patients under age 18 for adverse events.

Source: FDA, January 21, 2015

FDA Seeks More Reliable AEDs

The FDA will strengthen its review of automated external defibrillators (AEDs) to help improve the quality and reliability of potentially lifesaving devices with a history of malfunctions.

The agency issued a final order that will require AED manufacturers to submit premarket approval applications (PMAs), which will undergo a more rigorous review than that required to market AEDs in the past. The new reviews will focus on the critical requirements needed to ensure the safety and reliability of AEDs and their necessary accessories, including batteries, pad electrodes, adapters, and hardware keys for pediatric use.

AEDs are often stored in public locations for use in an emergency. From January 2005 through September 2014, the FDA received about 72,000 medical device reports associated with AED failures. Since 2005, manufacturers have conducted 111 recalls, affecting more than two million AEDs. Problems have included design and manufacturing issues, such as inadequate control of components purchased from other suppliers.

By requiring premarket approval for AEDs, the FDA will receive important information about the manufacturers’ quality systems. The agency will also inspect manufacturers’ facilities prior to approval. After approval, manufacturers will be required to submit to the FDA any changes made to the devices that affect safety or effectiveness, as well as annual reports on device performance.

AEDs now on the market will remain available. The FDA does not intend to enforce the PMA requirement for AEDs until July 29, 2016, as long as manufacturers notify the FDA of their intent to file a PMA by April 29, 2015. The FDA does not intend to enforce the PMA requirement for currently marketed, necessary AED accessories until January 29, 2020.

Source: FDA, January 28, 2015

Device Recall

Covidien Trellis 6 and Trellis 8

Because of a labeling error, Covidien is recalling the Trellis 6 and Trellis 8 Peripheral Infusion systems, which are used to treat blood clots in the veins or arteries of the arms, hands, legs, or feet.

Two balloons in the systems are inflated to isolate a clot. Medication is released between the balloons to shrink or dissolve the clot so it can be removed. A manufacturing error caused the balloon inflation ports to be mislabeled, which may cause a physician to deflate the balloons in the wrong order. If this happens, blood clots could potentially dislodge and move into the lungs.

From June 6, 2014, to November 13, 2014, 1,126 units were distributed in the U.S. Product, model, and lot numbers are available at Questions about this class I recall can be directed to Covidien customer service at 1-800-716-6700, 7 a.m. to 7 p.m. Central time.

Source: FDA, February 11, 2015


Kunj Gohil, PharmD, RPh

Name: G4 Platinum Continuous Glucose Monitoring System With Share

Manufacturer: Dexcom, San Diego, California

Approval Date: January 26, 2015

Purpose: This innovative system provides a platform for the sharing of blood-glucose information between a patient and a caregiver or physician through the use of a receiver and a smartphone application. These blood-glucose values, along with alerts, can be shared with up to five “followers” to allow real-time patient monitoring.

Description: Dexcom’s glucose-monitoring system comprises three components: a receiver used to measure blood-glucose levels; a mobile application used to share information such as glucose levels, abnormalities, and notifications; and a “follow” application that allows caregivers to receive any shared information.

Benefit: The G4 Platinum Continuous Glucose Monitoring System With Share is the first mobile strategy designed to help diabetes patients manage their chronic condition. With smartphone capabilities increasing rapidly, this new monitoring system can use a patient’s mobile device to log glucose readings quickly. Most importantly, the sharing capability will allow caregivers to monitor any abnormalities remotely and intervene as they see fit.


Name: FastForward Bone Tether Plate

Manufacturer: MedShape, Inc., Atlanta, Georgia

Approval Date: February 2, 2015

Purpose: This device is a primary component of a larger system used to correct bunions, typically associated with a foot deformity at the base of the big toe. A 3D printer is used to make a plate to bring the metatarsal bones closer together, alleviating the bunion that has formed.

Description: The FastForward Bone Tether Plate is part of the FastForward Bunion Correction System, which aims to correct deformities while preserving native bone anatomy. Three-dimensional printing is used to match the plate with the anatomy of the second metatarsal. Once the plate has been created, a procedure is performed to correct the bunion and bring the bones closer together.

Benefit: Bunion formation affects 23% of people ages 18 to 65 years annually. Traditional management includes cutting, realigning, and fusing bones within the foot to correct the deformity. This method can be associated with additional side effects and long recovery periods. The FastForward Bunion Correction System aims to spare bone structure while correcting the deformity. Specifically, the tether plate is printed to match a patient’s specific bone anatomy and removes the need for additional materials within the foot. MedShape hopes to expand its offerings in the future by using its 3D printing platform to make other implants.


Name: Maestro Rechargeable System

Manufacturer: EnteroMedics Inc., Saint Paul, Minnesota

Approval Date: January 14, 2015

Purpose: The Maestro system is intended to help patients lose weight.

Description: The system is made up of a neuroregulator disk, wire leads, and electrodes implanted surgically into the abdomen. Electrical impulses are sent to the abdominal vagus nerve to block nerve signals between the brain and the stomach. The vagus nerve helps regulate stomach emptying and tells the brain whether the stomach feels full or empty.

Benefit: Obesity has become one of the leading causes of preventable death and can increase the risk of death from all other causes. As the number of obese patients continues to grow, a need for effective weight-loss therapies and systems becomes apparent. The Maestro system provides patients with a new option to help them lose weight. This is the first system designed to block signals that control how hungry a patient feels, a concept also known as VBLOC (vagal blocking) therapy. This system has been tested in clinical trials and EnteroMedics has agreed to conduct a five-year post-approval study to collect additional efficacy and safety data.