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P T. 2016;41(2): 84-88,90-94,119
New Drugs/Drug News

New Drugs/Drug News/New Medical Devices February 2016

NEW DRUG APPROVALS

Zurampic for Hyperuricemia Associated With Gout

The FDA has approved lesinurad (Zurampic, AstraZeneca) to treat high levels of uric acid in the blood (hyperuricemia) associated with gout.

Lesinurad is to be used in combination with a xanthine oxidase inhibitor (XOI), a type of drug approved to reduce the production of uric acid in the body. Lesinurad helps the kidney excrete uric acid by inhibiting the function of transporter proteins involved in uric acid reabsorption.

The safety and efficacy of lesinurad (in combination with an XOI) were evaluated in three randomized, placebo-controlled studies involving 1,537 subjects who were treated for up to 12 months. The subjects treated with lesinurad and an XOI showed reduced serum uric acid levels compared with subjects given placebo.

Source: FDA, December 22, 2015

Vistogard for Chemotherapy Overdose

The FDA has cleared uridine triacetate (Vistogard, Wellstat Therapeutics) for the emergency treatment of adults and children who receive an overdose of the cancer treatment fluorouracil or capecitabine, or who develop certain severe or life-threatening toxicities within four days of receiving these cancer treatments.

The efficacy and safety of uridine triacetate were studied in 135 adult and pediatric cancer patients who were treated in two separate trials and had received an overdose of fluorouracil or capecitabine, or who had early-onset, unusually severe or life-threatening toxicities within 96 hours after receiving fluorouracil (not due to an overdose). Of those who were treated with uridine for overdose, 97% were still alive at 30 days. Of those treated with uridine for early-onset severe or life-threatening toxicity, 89% were alive at 30 days. In both studies, 33% of patients resumed chemotherapy in fewer than 30 days.

Source: FDA, December 11, 2015

Uptravi for PAH

Selexipag (Uptravi, Actelion Pharmaceuticals US) has been cleared for use in adults with pulmonary arterial hypertension (PAH), a chronic, progressive lung disease that can lead to death or the need for transplantation.

Selexipag belongs to a class of drugs called oral IP prostacyclin receptor agonists. The drug acts by relaxing muscles in the walls of blood vessels to reduce the elevated pressure in the vessels supplying blood to the lungs.

The safety and efficacy of selexipag were established in a long-term clinical study of 1,156 participants with PAH. Selexipag was shown to be effective in reducing hospitalization for PAH and the risks of disease progression compared with placebo. The participants were exposed to selexipag for a median period of 1.4 years.

Source: FDA, December 22, 2015

Basaglar for Type-2 Diabetes

The FDA has approved Basaglar (insulin glargine injection, Eli Lilly), a long-acting human insulin analogue, to improve glycemic control in adult and pediatric patients with type-1 diabetes mellitus and in adults with type-2 diabetes mellitus. Basaglar is the first insulin product approved through an abbreviated approval pathway under the Federal Food, Drug, and Cosmetic Act. It received tentative approval from the FDA in August 2014 and has now been granted final approval.

Source: FDA, December 16, 2015

Generic Approvals

Olopatadine HCl Ophthalmic Solution

Four companies have received FDA approval to market olopatadine hydrochloride ophthalmic solution USP, 0.1%: USV North America, Inc.; Apotex, Inc.; Novel Laboratories, Inc.; and Zach System, S.p.A. These are the first generic versions of Patanol Ophthalmic Solution (Alcon), a relatively selective H1 receptor antagonist and inhibitor of histamine release from the mast cell for topical administration to the eyes. The medication is used to treat the signs and symptoms of allergic conjunctivitis.

Sources: FDA, December 7, 2015, and Patanol prescribing information

Amikacin Sulfate Injection

The FDA has approved the application of Fresenius Kabi USA, LLC, to market amikacin sulfate injection USP, 250 mg/mL, a generic version of Amikacin Sulfate Injection USP (Eurohealth International SARL). Amikacin injection is a semisynthetic aminoglycoside antibiotic that is active against a broad spectrum of gram-negative organisms, including Pseudomonas, and some gram-positive organisms.

Sources: FDA, December 9, 2015, and Amikacin injection prescribing information

Fesoterodine Fumarate ER

Alkem Laboratories Ltd. has secured FDA approval to market fesoterodine fumarate extended-release tablets, 4 mg and 8 mg. This is the first generic version of Toviaz Extended-Release Tablets (Pfizer), a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

Sources: FDA, December 10, 2015, and Toviaz prescribing information

Levetiracetam

Generic 250-mg, 750-mg, and 1,000-mg levetiracetam tablets can be marketed by Secan Pharmaceuticals, Inc., the FDA has ruled. The brand-name product, Keppra (UCB Inc.), is indicated for adjunctive therapy for certain types of epileptic seizures. Keppra had estimated U.S. sales of $271 million in 2015, according to GlobalData.

Sources: FDA, December 16, 2015, and Keppra prescribing information

Busulfan Injection

The FDA has approved the marketing of busulfan injection, 6 mg/mL (10 mL single-dose vial) by Pharmaforce, Inc.—the first generic formulation of Busulfex injection (Otsuka Pharmaceutical). Busulfex is an alkylating drug indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.

Sources: FDA, December 22, 2015, and Busulfex prescribing information

Neostigmine Methylsulfate Injection

Neostigmine methylsulfate injection USP can be marketed in 5 mg/10 mL and 10 mg/10 mL strengths by Eurohealth International SARL. This marks the first generic version of Bloxiverz (Eclat Pharmaceuticals LLC), a cholinesterase inhibitor indicated for the reversal of the effects of nondepolarizing neuromuscular blocking agents after surgery.

Sources: FDA, December 28, 2015, and Bloxiverz prescribing information

NEW INDICATIONS

Xeomin for Upper Limb Spasticity

IncobotulinumtoxinA (Xeomin, Merz North America) now has FDA approval for the treatment of upper limb spasticity (ULS) in adults. In clinical studies, treatment with Xeomin in adults with ULS resulted in statistically and clinically significant improvements in muscle tone. The FDA first approved Xeomin in August 2010 for the treatment of adults with cervical dystonia and blepharospasm.

The approval of Xeomin for the treatment of adults with ULS was based on results from a randomized, placebo-controlled trial that showed significant improvements in two coprimary outcome endpoints: muscle tone (Ashworth Scale score) and the Investigator’s Global Impression of Change of the Primary Target Clinical Pattern (PTCP) at week 4. Both parameters showed statistical significance compared with placebo (P < 0.001 and P = 0.003, respectively).

Source: Merz, December 23, 2015

Gardasil 9 Use Extended To Males Ages 16 to 26

The FDA has approved an expanded age indication for Gardasil 9 (human papillomavirus [HPV] nine-valent vaccine, recombinant, Merck) to include use in males 16 through 26 years of age for the prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV types 6 and 11. Gardasil 9 is already approved for use in boys 9 through 15 years of age for the prevention of these diseases.

Gardasil 9 is also approved for use in girls and young women 9 through 26 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV types 6 and 11.

Gardasil 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of Gardasil 9 or Gardasil (human papillomavirus quadrivalent [types 6, 11, 16, and 18] vaccine, recombinant).

Source: Merck, December 15, 2015

NEW FORMULATIONS

Non-Alcohol Docetaxel Injection

The FDA has approved docetaxel injection, non-alcohol formula (Teikoku Pharma USA/Eagle Pharmaceuticals) for the treatment of breast cancer, non–small-cell lung cancer, prostate cancer, gastric adenocarcinoma, and head and neck cancer.

Docetaxel, a taxane product, was originally marketed by Sanofi-Aventis as Taxotere. Since its patent expiration in 2011, several generic versions have become available. Docetaxel injection is the first non-alcohol formulation approved in the U.S. It is available in the following presentations: 20 mg/1 mL in single-dose vials, and 80 mg/4 mL or 160 mg/8 mL in multiple-dose vials.

Source: FDA, December 28, 2015

First ER Chewable Tablet

The FDA has approved the first extended-release (ER) chewable tablet, developed by Tris Pharma. Prior ER tablets and capsules typically carried the warning “should not be chewed or crushed.”

The ER chewable tablets are an extension of Tris Pharma’s LiquiXR platform, a particulate-based technology in which hundreds of millions of tiny particles (about 100 microns) deliver drug over time. Controlled release is facilitated by a flexible particle coating.

The same particles can be used to formulate various oral ER dosage forms, such as liquid suspensions, dispersible tablets, and film strips. In addition, the chewable tablets can be scored like any immediate-release tablets.

Source: Tris Pharma, December 16, 2015

DRUGS UNDER REVIEW

Priority Review

Sofosbuvir/Velpatasvir for HCV

The FDA has granted priority review to the new drug application (NDA) for an investigational once-daily, fixed-dose combination of the nucleotide analogue polymerase inhibitor sofosbuvir (Sovaldi, Gilead Sciences) and velpatasvir, an investigational pan-genotypic NS5A inhibitor, for the treatment of chronic genotype 1–6 hepatitis C virus (HCV) infection.

Gilead Sciences filed the NDA for the combination in October 2015, and the FDA set a target action date of June 28, 2016. The agency also assigned the combination a breakthrough therapy designation, which is granted to investigational medications that may offer major advances in treatment over existing options.

Source: Gilead Sciences, January 4, 2016

Breakthrough Therapies

Setmelanotide for a Type of Obesity

The FDA has awarded breakthrough therapy status to setmelanotide (RM-493, Rhythm), an investigational melanocortin-4 receptor (MC4R) agonist, for the treatment of pro-opiomelanocortin deficiency obesity. Setmelanotide is in phase 2 clinical trials for the treatment of rare genetic disorders of obesity caused by MC4 pathway deficiencies. MC4 is a key pathway in humans that regulates energy expenditure, homeostasis, and appetite.

Setmelanotide also received an orphan drug designation for the treatment of Prader–Willi syndrome (PWS). A hallmark of PWS is severe hyperphagia, an overriding physiological drive to eat, leading to severe obesity and other complications. Hyperphagia and obesity are the greatest threats to PWS patients’ health, and these patients are likely to die prematurely as a result of choking, stomach rupture, or complications caused by morbid obesity. No approved treatment is available for the obesity and hyperphagia associated with PWS.

Source: Rhythm, January 7, 2016

VTS-270 for Niemann-Pick Type C1

VTS-270 (Vtesse, Inc.), a modified form of cyclodextrin, has received the FDA’s breakthrough therapy status for the treatment of Niemann-Pick type C1 disease. The agency had previously granted an orphan drug designation to VTS-270, which is being evaluated in a pivotal phase 2b/3 clinical trial.

Niemann-Pick type C genes (NPC1 and NPC2) code for proteins that are part of the cholesterol metabolism pathway in cells. VTS-270 targets cholesterol and sphingolipid storage. Preliminary studies have demonstrated that VTS-270 can help cholesterol bypass the NPC1/NPC2 pathway, promoting transport of the cholesterol that would normally accumulate in the lysosomes of cells that have the NPC1 or NPC2 mutation. This restores the cell’s normal cholesterol metabolism and regulation.

Source: Vtesse, Inc., January 6, 2016

BI 1482694 for Lung Cancer

The FDA has granted a breakthrough therapy designation to BI 1482694 (Boehringer Ingelheim), an investigational third-generation epidermal growth factor receptor (EGFR) mutant-specific tyrosine kinase inhibitor (TKI). The designation was based on results from a phase 1/2 clinical trial that evaluated the treatment of patients with T790M mutation-positive non–small-cell lung cancer whose tumors no longer responded to currently available EGFR-directed therapies.

BI 1482694 was developed specifically to target tumors with T790M mutations, the most common resistance mechanism that develops in response to treatment with EGFR TKIs. It is found in approximately 50% to 60% of patients who have received EGFR TKI therapy.

Source: Boehringer Ingelheim, December 21, 2015

Orphan Drug Designations

WT1 Cancer Vaccine for AML

The FDA has granted orphan drug status to a Wilm’s tumor gene 1 (WT1) cancer vaccine candidate (Sellas Life Sciences Group) for the treatment of patients with acute myeloid leukemia (AML).

Median overall survival (OS) of approximately four years was achieved in a phase 2 trial of the WT1 analog peptide vaccine in adult patients with AML. Similarly, in a previous phase 1 AML study, the WT1 vaccine resulted in median OS of more than three years. When combined, the results from the phase 1 and phase 2 studies demonstrated a two-year OS rate of 79% in adult AML patients. Both trials studied the WT1 vaccine in combination with Montanide adjuvant plus granulocyte macrophage colony-stimulating factor in AML patients with a first complete response who completed any planned post-remission therapy. A total of 31 patients were enrolled in the two studies, which were conducted at the Memorial Sloan Kettering Cancer Center.

Based on these findings, Sellas plans to initiate a pivotal phase 3 trial of its WT1 vaccine candidate in AML patients in early 2016.

Source: Sellas Life Sciences Group, January 11, 2016

GPX-150 for Sarcoma

The FDA has granted an orphan drug designation to GPX-150 (Gem Pharmaceuticals), a noncardiotoxic analogue of the anthracycline antibiotic doxorubicin, which is being evaluated in an open-label, phase 2 clinical trial in patients with soft-tissue sarcoma (STS). Final safety and efficacy data expected to be available from this study by the fourth quarter of 2016.

GPX-150 intercalates DNA and impedes the activity of topoisomerase II, inducing single- and double-stranded breaks in DNA; inhibiting DNA replication and/or repair, transcription, and protein synthesis; and activating tumor cell apoptosis. The drug’s chemical structure is 5-imino-13-deoxydoxoubicin.

STS includes a group of malignancies that affect tissues such as fat, muscles, nerves, and tendons. According to the American Cancer Society, approximately 12,000 new cases of STS occur in the U.S. annually, with about 5,000 deaths.

Source: Gem Pharmaceuticals, January 6, 2016

Ionis-HTTRx for Huntington’s Disease

The FDA has given orphan drug status to Ionis-HTTRx (Ionis Pharmaceuticals) for the treatment of patients with Huntington’s disease (HD). Ionis-HTTRx is the first therapy to enter clinical development that is designed to directly target the cause of the disease by reducing the production of the huntingtin (HTT) protein.

HD is a rare genetic, progressive neurological disease resulting in deterioration in mental abilities and physical control. In this disease, the gene that encodes for the HTT protein contains a trinucleotide sequence that is repeated in the gene more than 36 times. The resulting HTT protein is toxic and gradually damages neurons in the brain.

Source: Ionis Pharmaceuticals, January 5, 2016

Intranasal Diazepam for Seizures

The FDA has granted an orphan drug designation to NRL-1 (intranasal diazepam, Neurelis, Inc.) for the treatment of pediatric, adolescent, and adult epilepsy patients who experience acute repetitive seizures.

NRL-1 is a proprietary formulation of diazepam, delivered via an already-marketed nasal sprayer, being developed for the management of pediatric and adult patients who require intermittent use of diazepam to control bouts of acute repetitive seizure activity. NRL-1 demonstrated high bioavailability and low variability from dose to dose in clinical trials, and the treatment was well tolerated.

It has been estimated that 30% to 40% of epilepsy patients in the U.S. are uncontrolled on oral therapy and are at risk for acute breakthrough seizures.

Source: Neurelis, Inc., December 21, 2015

DRUG SAFETY ISSUES

Dosing Errors With Noxafil

Differences in dosing regimens between the two oral formulations of the antifungal agent posaconazole (Noxafil, Merck) have resulted in dosing errors, according to the FDA. To help prevent additional medication errors, the drug labels have been revised to indicate that the two oral formulations (an oral suspension and a delayed-release tablet) cannot be directly substituted for each other but require a change in dose. Direct milligram-for-milligram substitution of the two formulations may result in drug levels that are lower or higher than needed to treat certain fungal infections effectively.

Since the approval of posaconazole delayed-release tablets in November 2013, the FDA has received 11 reports of the wrong oral formulations being prescribed and/or dispensed to patients. One case resulted in death, and an additional case resulted in hospitalization. According to the reports, these outcomes were a result of health care professionals not knowing that the two oral formulations cannot be substituted for each other without adjusting the dose because of differences in how the medication is absorbed and handled by the body.

Source: FDA, January 4, 2016

FDA Eliminates REMS for Rosiglitazone in Diabetes

The FDA has eliminated the risk evaluation and mitigation strategy (REMS) for rosiglitazone-containing type-2 diabetes medications, which are approved as Avandia, Avandamet, and Avandaryl (all marketed by GlaxoSmithKline) as well as generic products. The REMS is no longer necessary to ensure that the benefits of rosiglitazone medications outweigh their risks, according to the agency.

In 2013, the FDA required removal of the prescribing and dispensing restrictions for rosiglitazone medications after determining that data did not demonstrate an increased risk of heart attack with rosiglitazone drugs compared with the standard type-2 diabetes medications metformin and sulfonylurea.

Source: FDA, December 16, 2015

CLINICAL TRIAL NEWS

Data Support Efficacy of Cometriq in Renal Cancer

Positive data have been reported from subgroup analyses of a phase 3 pivotal trial comparing cabozantinib (Cometriq, Exelixis, Inc.) with everolimus (Afinitor, Novartis) in 658 patients with renal cell carcinoma (RCC) who have experienced disease progression after treatment with a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKI).

As assessed by an independent radiology committee, median progression-free survival across all enrolled patients was 7.4 months for the cabozantinib arm compared with 3.9 months for the everolimus arm, corresponding to a 48% reduction in the rate of disease progression or death for cabozantinib compared with everolimus (hazard ratio, 0.52; P < 0.001). The objective response rate across all 658 patients was 17% for cabozantinib and 3% for everolimus. The median duration of response for cabozantinib was not reached compared with 7.4 months for everolimus.

The observed benefits were independent of the location and number of organ metastases; the patient’s tumor burden; the type, duration, and number of prior VEGF receptor TKI therapies; and prior programmed death-1/programmed death ligand-1 therapy.

Source: Exelixis, Inc., January 4, 2016

Parkinson’s Drug ADS-5102 Shows Promise in Phase 3 Trial

A phase 3 study evaluating the investigational compound ADS-5102 (amantadine hydrochloride, Adamas Pharmaceuticals) for the treatment of levodopa-induced dyskinesia (LID) associated with Parkinson’s disease has met its primary endpoint.

Results from this randomized, placebo-controlled study showed a statistically significant reduction (P = 0.0009) in LID at 12 weeks in patients treated with ADS-5102 extended-release capsules compared with those given placebo, as assessed by the Unified Dyskinesia Rating Scale. This represents a 23% reduction in LID in the ADS-5102 group. The reduction in LID was maintained at 24 weeks (P = 0.0008), a key secondary analysis.

ADS-5102 extended-release capsules are intended for once-daily administration at bedtime.

Source: Adamas Pharmaceuticals, December 23, 2015

Cosentyx Improves Ankylosing Spondylitis

Results from the phase 2 MEASURE 1 and MEASURE 2 trials of secukinumab (Cosentyx, Novartis), an interleukin-17A antagonist, in patients with ankylosing spondylitis (AS) have been published in the New England Journal of Medicine. These pivotal studies demonstrated significant clinical improvements with secukinumab compared with placebo in reducing the signs and symptoms of active AS.

In both studies, the primary endpoint was the proportion of patients meeting the Assessment of Spondyloarthritis International Society 20 (ASAS20) response criteria at week 16 with secukinumab 150 mg. In the MEASURE 1 and MEASURE 2 trials, ASAS20 response rates with secukinumab compared with placebo at week 16 were 61% versus 29% (P < 0.001) and 61% versus 28% (P < 0.001), respectively. Patients enrolled in these studies were either inadequate responders to or intolerant of medications targeting tumor necrosis factor (TNF) or had not been previously treated with anti-TNF therapies.

Source: Novartis, December 23, 2015

Binimetinib Meets Primary Goal in Melanoma Trial

Positive results have been reported from an ongoing phase 3 trial of binimetinib (Array BioPharma) in patients with advanced NRAS-mutant melanoma. The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine. The median PFS in the binimetinib arm was 2.8 months, compared with 1.5 months in the dacarbazine arm (P < 0.001).

MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway. Research has shown that this pathway regulates several key cellular activities, including proliferation, differentiation, migration, survival, and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including non–small-cell lung cancer, melanoma, and colorectal, ovarian, and thyroid cancers. Binimetinib is a small-molecule MEK inhibitor that targets key enzymes in this pathway.

Source: Array BioPharma, December 16, 2015

KIT-302 More Effective Than Amlodipine in Hypertension

A phase 3, double-blind, placebo-controlled trial of the drug candidate KIT-302 (Kitov Pharmaceuticals) successfully met its primary efficacy endpoint. Data from the study showed that KIT-302 was more effective at reducing hypertension than the widely used hypertension treatment amlodipine besylate. A new drug application for marketing approval of KIT-302 is expected to be filed with the FDA in the second half of 2016.

KIT-302 simultaneously treats the pain caused by osteoarthritis (OA) and hypertension, which is a common adverse effect of stand-alone drugs that treat OA pain. KIT-302 consists of two FDA-approved drugs: celecoxib (Celebrex, Pfizer) for the pain caused by OA, and amlodipine besylate for hypertension.

Source: Kitov Pharmaceuticals, December 15, 2015

Positive Data for Cetuximab And Infliximab Biosimilars

Phase 3 clinical trials of STI-001, a biosimilar antibody for cetuximab (Erbitux), and STI-002, a biosimilar antibody for infliximab (Remicade), have been completed successfully. Both STI-001 and STI-002 met their primary endpoints in the confirmatory, randomized, controlled studies. Both products are being developed by Sorrento Therapeutics and its partner MabTech Ltd.

STI-001, a chimeric monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), was used for treatment of EGFR-expressing metastatic colorectal carcinoma patients in combination with irinotecan versus irinotecan alone. The combination therapy showed significant improvement compared with chemotherapy alone in the overall response rate (32.9% versus 12.8%, respectively) and progression-free survival (5.6 versus 3.2 months) as well as longer overall survival (14.1 versus 13.4 months).

STI-002, a chimeric monoclonal antibody produced in Chinese hamster ovary cell lines, binds to soluble and transmembrane forms of tumor necrosis factor (TNF)-alpha and inhibits TNF-alpha binding to receptors, thereby neutralizing the biological activity of TNF-alpha. In a phase 3 study involving 330 patients with rheumatoid arthritis, STI-002 improved pain symptoms, physical functioning, quality of life, and inflammatory markers while inhibiting bone and joint damage.

Source: Sorrento Therapeutics, Inc., January 11, 2016

Etanercept Biosimilar Meets Goal in Late-Stage Study

CHS-0214 (Coherus BioSciences/Baxalta Inc.), a proposed biosimilar of etanercept (Enbrel, Amgen), met its primary endpoint in a phase 3, double-blind, randomized, controlled trial. This ongoing, 52-week study is evaluating the efficacy and safety of CHS-0214 compared with etanercept in patients with moderate-to-severe rheumatoid arthritis (RA) that has been inadequately controlled with methotrexate alone.

The study’s primary efficacy endpoint was the proportion of subjects achieving a 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 24. This endpoint was within the prespecified margins for demonstrating the equivalence of CHS-0214 compared with etanercept. There were no clinically meaningful differences in the safety and immunogenicity profiles of the two products.

Source: Baxalta, January 11, 2016

RESEARCH BRIEFS

Adjunctive Corticosteroids May Offer CAP Advantages

Researchers from Switzerland’s Geneva University Hospitals and Geneva Faculty of Medicine performed a meta-analysis of the risks and advantages of adjunctive therapy with corticosteroids for patients with community-acquired pneumonia (CAP). They reviewed 14 trials involving 2,077 patients who were treated either with adjunctive corticotherapy or antimicrobial therapy.

Eight studies, with 1,624 patients, reported length of stay. Researchers found a mean of nine days for patients treated with adjunctive corticotherapy versus 10.6 days for those treated with antimicrobial therapy alone. Four studies, with 1,163 patients, reported time to clinical stability; the mean was 3.3 days for patients on adjunctive corticotherapy, compared with 4.3 days for antimicrobial treatment alone.

Four studies, with 304 patients, reported on severe complications (requiring vasopressors or mechanical ventilation); three times as many patients on antimicrobial therapy had severe complications (37.4% versus 12.1%). In four other studies, 3.6% of 138 patients on adjunctive corticosteroids needed vasopressors, compared with 14.5% of 128 patients on antimicrobial therapy. And in seven studies reporting on mechanical ventilation, 5.3% of 619 adjunctive corticosteroid patients required ventilation, compared with 12.1% of 580 on antimicrobials.

The researchers found no benefit in 30-day mortality, but mortality was significantly reduced in a subgroup of patients with severe CAP. Adverse events seem to be infrequent and short-lasting, although the risk of hyperglycemia was higher among patients on corticosteroids.

Source: PLoS One, December 7, 2015

Warfarin May Interact With Sulfonylureas

Citing the “first direct real world evidence,” researchers from Harvard and the University of Southern California warn that warfarin may potentiate the hypoglycemic action of some sulfonylureas.

In a retrospective cohort analysis of 465,918 older adults using glipizide and glimepiride, the researchers found that hospital admissions or emergency department visits for hypoglycemia and related diagnoses were more common among the 71,533 patients who were also using warfarin. Concurrent use of warfarin and glipizide or glimepiride was also associated with other hypoglycemia-related diagnoses, such as fractures due to falls. The associations were strongest for patients using warfarin for the first time and for those ages 65 to 74 years.

The problem seems to be a drug–drug interaction, the researchers say. They found no associations of hypoglycemia rates with concurrent use of statins and glipizide or glimepiride or between war-farin and other diabetes drugs.

Evidence suggests two possible mechanisms for the higher risk of hypoglycemia. One is through displaced protein binding: The warfarin displaces the sulfonylurea, increasing its plasma drug concentration and drug activity. A second possibility is that because the drugs are all primarily metabolized by the CYP2C9 hepatic metabolic pathway, the larger doses of warfarin may interfere with metabolism of sulfonylurea.

The potential interaction has not been widely appreciated, the researchers say, and health care professionals are not routinely alerted when patients on sulfonylureas start warfarin treatment. They suggest that, just as a lower initial dose of warfarin is advised for older patients to mitigate the risk of bleeding, the dose should be lower for older patients who start warfarin while taking glipizide or glimepiride.

Source: BMJ, December 7, 2015

Antihypertensives, Falls, and Fractures

High blood pressure and systolic hypotension have been linked to falls, reduced bone mineral density, and hip fractures. But antihypertensive drugs have, in observational studies, seemed to increase the risk of falls and hip fractures—even though meta-analyses found no associations between long-term treatment and falls. Indeed, research has suggested benefits of thiazides, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors, such as direct stimulation of osteoblasts. University of Bergen researchers note, however, that previous studies of antihypertensives and hip fracture have focused on diuretics and beta blockers; widely used combination drugs have not been considered.

The Norwegian researchers looked at data from 906,422 people born before 1945. Over about six years, 39,938 people (4.4%) fractured their hips. Thiazides, beta blockers, calcium-channel blockers, angiotensin II receptor blockers, and certain combination products containing ACE inhibitors/thiazides and angiotensin II receptor blockers/thiazides reduced the risk of hip fracture. Loop diuretics and ACE inhibitors increased the risk of fracture in people younger than 80 years of age but reduced risk in those older than 80. The increased risk in younger people may be due to the “more-ill-user effect,” the researchers say, because those drugs are frequently given to relatively frail people with heart failure.

All the drugs (except loop diuretics) were more protective for men than women. Most antihypertensive drugs appear to be beneficial for bone health in both sexes, the researchers say, but risk differences were not eliminated. Sex hormones interfere with bone metabolism, which puts postmenopausal women at a much higher risk of hip fracture. In this study, 72% of patients who had a hip fracture were women.

New users of loop diuretics also had a higher risk of hip fracture, particularly in the first two weeks. The numbers were relatively small, however, and the researchers say their findings must be interpreted with caution. They also cite a recent study that linked loop diuretics with hyponatremia and a higher risk of osteoporotic fractures.

Source: BMC Geriatrics, December 1, 2015

Herpes Zoster Boosters Needed?

Herpes zoster (HZ) vaccine is mostly effective—in clinical trials, it reduced the risk of herpes zoster by at least 60%, the burden of illness by 61%, and postherpetic neuralgia (PHN) by 67%. But surveillance studies have shown that the vaccine’s effectiveness declines within five years, say researchers who reviewed six studies on the vaccine.

While efficacy was 60% or higher among younger cohorts during year 1 post-vaccination, the response was significantly lower among patients 70 years of age and older. Moreover, vaccine efficacy waned considerably, the researchers say, after the first year of vaccination regardless of age or whether efficacy was measured by HZ incidence or burden of illness. However, some research found the vaccine’s efficacy against PHN increased in patients older than 69 years of age.

Long-term persistence of zoster vaccine efficacy hasn’t been studied in patients ages 50 to 59—but those are the patients who are most at risk of shingles around the time the vaccine may be declining in effectiveness. People who reach 80 years of age have a 25% to 50% lifetime risk of developing HZ.

The researchers say their findings raise the question of whether patients will need revaccination. Until that’s established, they suggest advising patients that the vaccine loses significant and predictable protection after five to eight years.

Source: Clinical Therapeutics, November 2015

COPD and Sleep Disturbances

Exacerbations in chronic obstructive pulmonary disease (COPD) can impair pulmonary function, respiration, quality of life, and functional status—but little is known about their relationship to sleep. To fill this gap, researchers assessed sleep variables in a substudy of an observational longitudinal study.

Patients were followed for about six months. During that time, 15 of 17 patients had 27 symptom-defined exacerbations and eight had nine clinically reported exacerbations. Two exacerbations required hospitalization. One-quarter of the study days were exacerbation days.

The Stanford Sleepiness Scale score was significantly higher during exacerbations. Patients also had significantly less total sleep time and poorer sleep efficiency. Objective awakenings greatly exceeded subjective awakenings regardless of exacerbations, but not significantly. None of the four variables—sleep time, sleep efficiency, objective awakenings, and subjective awakenings—were strongly associated with daytime sleepiness. The study did not compare COPD patients to people without COPD, but the researchers found total sleep time and sleep efficiency “substantially worse” than reported for people with insomnia and older adults.

Whether the sleep disturbances can be considered clinically meaningful or whether the changes in sleep time and efficiency are causally related to sleepiness, the researchers say, are puzzles for a larger study to address.

Source: Chronic Respiratory Disease, November 2015

Can Social Media Improve Chronic Disease Care?

It’s time to harness the power of social media to help patients with chronic diseases, say researchers, who reviewed 42 studies using a novel taxonomy that organized results by domains of support, education, diagnosis, disease management, and disease modification.

Their analysis revealed gaps, they say; filling those gaps could prove valuable. For instance, they found that the studies focused mostly on just five technology platforms: Facebook, blogs, Twitter, Wikipedia/wikis, and YouTube—and of those, 69% concentrated on Facebook and blogs. By far the most attention (86%) was paid to cancer, depression, and obesity.

Based on their study, the researchers say contemporary social media are mostly likely to improve chronic disease care when used to provide social, emotional, or experiential support. Almost half of the studies suggested that social media offer benefits to patients with chronic disease, such as support (via blogs) or disease modification (via Facebook). Insights such as those, the researchers say, could help clinicians determine which social media might be most useful in improving patient care.

The studies provide valuable lessons about the plusses of each platform, the researchers say. For instance, one study found that Facebook groups are useful for weight loss and exercise because they provide a multimodal platform to access content, demonstrate skills, monitor progress, and organize virtual or live groups. By the same token, blogs were important sources of support for cancer patients.

The researchers say few studies suggest any harm from using social media technology in chronic disease care. On the other hand, they found no high-quality data, quantitative or qualitative, to support the use of social media within the domains of diagnosis or education.

Source: American Journal of Medicine, December 2015

DEVICE APPROVALS

Animas Vibe Insulin Pump For Children and Adolescents

The FDA has expanded the labeling for the Animas Vibe insulin pump and continuous glucose monitoring system (Animas Corporation/Johnson & Johnson) to include the management of diabetes in children and adolescents 2 to 17 years of age. The system was originally approved in December 2014 for use in adults (18 years of age or older).

The Animas Vibe system allows patients and their caregivers to view glucose data and to administer insulin directly from the pump, making it possible to fine-tune insulin delivery to help manage patients’ diabetes. The system includes the Dexcom G4 platinum sensor, which is indicated for detecting trends and tracking patterns in persons 2 years of age and older.

Source: Animas Corporation, January 11, 2016

Fusion Implant System For Extremities Surgery

Bio2 Technologies, Inc., has received 510(k) clearance from the FDA for its Fusion implant system for interphalangeal fusion, fracture repair, and osteotomies of the toes, fingers, and other small bones in the presence of appropriate immobilization.

The implants are constructed with the company’s Vitrium biomaterial, which is composed of bioactive glass, a resorbable material with a well-studied mechanism of action and a long track record of safe clinical use. After years of research and preclinical testing, Bio2 Technologies has applied its proprietary technology to produce a rigid, bioactive, and osteoconductive material with an interconnected porous structure that facilitates the ingrowth and remodeling of healthy bone.

Source: Bio2 Technologies, January 11, 2016

“Follow Me” Image-Guided Software for Robotic Surgery

The FDA has cleared new software designed for minimally invasive robotic surgery. The Follow Me software, developed by Medical Surgery Technologies (MST), allows an image-guided laparoscope to follow laparoscopic surgical tools without manual control.

Using MST’s image-analysis software, surgeons can virtually tag the surgical tools within the surgical cavity. The system interacts with the surgeon’s in vivo movements and gestures, guiding the robotic laparoscope positioner to follow the surgeon’s tools in real time.

Source: Medical Surgery Technologies, January 6, 2016

Fenix Fecal Continence Restoration System

The FDA has approved the Fenix continence restoration system (Torax Medical, Inc.) to treat fecal incontinence in patients who are not candidates for, or have previously failed, medical or other surgical options.

The system has three components: an implant, an anal sphincter sizing tool, and an introducer tool. The implant is a series of titanium beads with magnetic cores that are connected by titanium wires to form a ring shape. The attractive force of the magnetic beads augments the anal sphincter to minimize involuntary opening of the anal canal, thereby reducing the likelihood of severe fecal incontinence. The sizing tool is used to associate the anal sphincter size to an appropriate implant. The introducer tool is used to guide the sizing tool and the implant into position.

Source: FDA, December 18, 2015

Dario Blood Glucose Monitoring System

The FDA has granted 510(k) clearance for the Dario blood glucose monitoring system (LabStyle Innovations Corp.), including its components, the Dario blood glucose meter, Dario blood glucose test strips, Dario glucose control solutions, and the Dario app on the Apple iOS 6.1 platform and higher.

The Dario blood glucose monitoring system is indicated for the quantitative measurement of glucose in fresh capillary whole-blood samples drawn from the fingertips. The system helps people with diabetes monitor their blood sugar levels and to proactively manage their diabetes using their smartphone. Dario connects via a headphone jack to turn a mobile device into a glucose monitor, and it incorporates a lancing device and test strips together with the meter in a portable device to take blood glucose measurements on the spot. Unlike conventional glucose monitors, there is no carrying case or batteries.

Source: LabStyle Innovations Corp., December 22, 2015

NxTAG Respiratory Pathogen Panel

The FDA has cleared the NxTAG respiratory pathogen panel (Luminex Corporation), which detects 20 clinically relevant viral and bacterial respiratory pathogens, including the atypical bacteria Chlamydophila pneumoniae and Mycoplasma pneumonia. The panel is the only respiratory assay that allows laboratories to simultaneously detect 20 respiratory pathogens in a single closed-tube system in a format that scales to accommodate the changes in throughput needed to respond to seasonal changes in demand, especially during the flu season.

Source: Luminex Corporation, December 18, 2015

Omnigraft for Foot Ulcers Related to Diabetes

The FDA has approved a new indication for the Omnigraft dermal regeneration matrix (Integra LifeSciences Corporation) to treat certain diabetic foot ulcers. The matrix device, which is made of silicone, cow collagen, and shark cartilage, is placed over the ulcer and provides an environment for new skin and tissue to regenerate and heal the wound.

The FDA first approved the Integra dermal regeneration template (which the company now also calls Omnigraft) in 1996 for the treatment of life-threatening burn injuries when the use of a patient’s own skin for a graft was not possible. In 2002, the Integra dermal regeneration template was approved for a new indication to treat patients undergoing reconstructive surgery for burn scars when they cannot have skin grafts. Now, Omnigraft is approved to treat certain diabetic foot ulcers that last for longer than six weeks and do not involve exposure of the joint capsule, tendon, or bone, when used in conjunction with standard diabetic ulcer care.

Source: FDA, January 7, 2016

LifeVest Wearable Defibrillator for Children

The FDA has approved a new indication for the LifeVest wearable cardioverter defibrillator (Zoll Manufacturing Corporation). The LifeVest is now approved for some children who are at risk for sudden cardiac arrest but are not candidates for an implantable defibrillator because of certain medical conditions or lack of parental consent. The device was first approved in 2001 for use in adults (18 years of age and older).

While many automated external defibrillators (which require a second person to operate them) have been cleared for use in children, LifeVest is the only one that is worn by the patient and that monitors the heart continuously for arrhythmias. LifeVest responds automatically if it senses the need to deliver a shock, restoring a life-sustaining heartbeat.

Source: FDA, December 17, 2015

Infuse Bone Graft For Spine Surgery

Infuse Bone Graft (Medtronic) has been approved for the following additional indications: 1) use in oblique lateral interbody fusion (OLIF)-51 procedures with certain sizes of the polyetheretherketone (PEEK) Perimeter implant at a single level from L5 to S1; 2) use in OLIF-25 procedures with certain sizes of the PEEK Clydesdale implant at a single level from L2 to L5; and 3) use in anterior lumbar interbody fusion (ALIF) procedures with certain sizes of the PEEK Perimeter implant at a single level from L2 to S1.

Infuse Bone Graft is used with certain Medtronic interbody fusion devices to treat lumbar degenerative disc disease. The active ingredient (rhBMP-2) is a manufactured version of an endogenous protein that promotes new bone growth. During surgery, the product is applied to an absorbable collagen sponge, which delivers the rhBMP-2 to the implant site and acts as a scaffold for the formation of new bone.

Source: Medtronic, December 11, 2015

DEVICE NEWS

Single-Use Laryngoscope Eliminates Reprocessing

OBP Medical has announced the availability of an improved version of its Sure-Scope, a single-use, one-piece laryngoscope with a built-in LED light source. According to the company, the design eliminates the time and expense of reprocessing and reduces the risk of cross-contamination in medical settings. The device comes out of its package sterile and ready to use, with no additional parts or assembly required. After a single patient use, the entire device—handle, blade, and light—is thrown away. By using the device, medical facilities can cut their cost per intubation by as much as 64%, OBP says.

Source: OBP Medical, January 11, 2016

Prior Authorization Required For Some Medical Equipment

The Centers for Medicare and Medicaid Services (CMS) has issued a final rule on the ordering of durable medical equipment, prosthetics, orthotics, and supplies (DMEPOS). The new rule establishes a prior authorization process for DMEPOS that are often subject to unnecessary use. It also authorizes the creation of a master list of DMEPOS items potentially subject to prior authorization.

Examples of durable medical equipment include hospital beds, oxygen tents, and wheelchairs. The CMS defines prosthetic devices as devices (other than dental) that replace all or part of an internal body organ. Examples of such devices include cochlear implants, electrical continence aids, electrical nerve stimulators, and tracheostomy speaking valves. Orthotics include leg, arm, back, and neck braces; and artificial legs, arms, and eyes.

Sources: FierceHealthFinance, January 7, 2016; and Federal Register, December 30, 2015

Decipher Test Predicts Prostate Cancer Metastasis

The first validation data for the Decipher prostate cancer classifier (GenomeDx Biosciences) have supported its use in the analysis of diagnostic needle core biopsies to help guide the management of men newly diagnosed with prostate cancer. The test accurately predicted 10-year postoperative metastasis from a genomic analysis of diagnostic biopsy specimens. Decipher scores were evaluated from primarily low- and intermediate-risk patients with available needle biopsy tissue who went on to receive radical prostatectomy at Cleveland Clinic.

The evaluation of Decipher in 57 patients yielded a c-index of 0.80 for the prediction of metastasis at 10 years compared with 0.75 for National Comprehensive Cancer Network (NCCN) risk criteria alone. A combined model consisting of Decipher and NCCN risk criteria improved the accuracy to yield a c-index of 0.88. A multivariable analysis found that Decipher was the only significant predictor of metastasis when adjusting for age, preoperative prostate-specific antigen (PSA), and biopsy Gleason score (P = 0.02).

Source: GenomeDx Biosciences, January 7, 2016

Launch of L-Dex System for Lymphedema Assessment

ImpediMed Ltd. has announced the U.S. commercial launch of its L-Dex system to aid in the clinical assessment of lymphedema. This follows a successful pilot program involving six U.S. cancer centers, a dedicated current procedural terminology (CPT) category I code allowing physicians to seek reimbursement beginning in January 2015, and a revised FDA clearance in May 2013.

L-Dex is the first product of its kind to use bioimpedance spectroscopy, a noninvasive system for accurately measuring tissue composition and fluid status, to identify lymphedema up to 10 months before there is evidence of limb swelling. Early detection and subsequent intervention may help prevent the progression of the disease and, in some instances, even reverse it, according to the company.

Through electrodes placed on the arm and leg, L-Dex sends a small, imperceptible current using 256 frequency spectra through tissue measuring extracellular fluid. Using a scoring system, oncologists, breast cancer surgeons, and other health care providers can determine in seconds the amount of resistance from one point to the other and thus identify the onset of extracellular fluid accumulation.

Source: ImpediMed, January 7, 2016

FDA Tightens Requirements For Transvaginal Mesh

The FDA has issued two final orders to strengthen the data requirements for surgical mesh to repair pelvic organ prolapse (POP) transvaginally. The agency issued one order to reclassify these medical devices from class II, which generally includes moderate-risk devices, to class III, which generally includes high-risk devices. The second order requires manufacturers to submit a premarket approval (PMA) application to support the safety and effectiveness of surgical mesh for the transvaginal repair of POP.

The orders will require manufacturers to address safety concerns, including severe pelvic pain and organ perforation, through a PMA pathway to demonstrate safety and effectiveness. The actions apply only to mesh devices marketed for the transvaginal repair of POP. They do not apply to surgical mesh for other indications, such as stress urinary incontinence or abdominal repair of POP.

Source: FDA, January 4, 2016

New Biochip Could Permit Point-of-Care Blood Counts

Researchers at the University of Illinois at Urbana–Champaign have developed a biosensor that can count blood cells electrically using only a single drop of blood. The gold standard routinely used in hospitals and testing laboratories is a hematology analyzer, which is large and expensive.

The microfluidic device electrically counts the different types of blood cells based on their size and membrane properties. To count leukocytes and their differentials, red blood cells are selectively lysed, and the remaining white blood cells are individually counted. Specific cells, such as neutrophils, are counted using multifrequency analysis, which probes the cells’ membrane properties. For red blood cells and platelets, 1 mcL of whole blood is diluted with phosphate buffered saline on the chip, and the cells are counted electrically. The total time for measurement is less than 20 minutes.

Source: World Scientific Publishing, December 18, 2015

Positive Results Reported For Dry Eye Assay

A prospective U.S. study has assessed the efficacy of the TeaRx multiassay test (BioLight Israeli Life Sciences Investments Ltd.) in evaluating the components of tears in patients with dry eye syndrome (DES). A total of 74 subjects were evaluated using a composite of four established benchmark tests for the assessment of DES. The subjects were also evaluated using the TeaRx assays.

The study results demonstrated sensitivity of 86%, specificity of 87%, and a positive predictive value of 87% for the TeaRx multiassay test. The results also indicated that the test, which incorporates a combination of tear constituents originating from different locations in the eye, may provide a more accurate diagnostic output than already-marketed DES tests.

Source: BioLight, January 7, 2016

Scientists Improve Video Pills To Assist Cancer Detection

Researchers at the University of Glasgow, Scotland, have found a way to make cameras that can be swallowed more effective at detecting cancers of the throat and gut. Until now, these systems, known as video pills, have relied on illuminating the patient’s innards using a small light source, thereby restricting clinicians to conclusions based on what they can see in the spectrum of visible light. Using an advanced semiconductor single-pixel imaging technique, the Scottish team has created fluorescence imaging in a small pill form for the first time. In addition to expanding the diagnostic capabilities of video pills, the new technology could also be used to help track antibodies used to label cancer in the human body, creating a new way to detect cancer, according to research associate Dr. Mohammed Al-Rawhani.

Source: University of Glasgow, December 18, 2015