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P T. 2016;41(3): 144-148, 153-158, 161, 194

New Drugs/Drug News/New Medical Devices March 2016

NEW DRUG APPROVALS

Adzenys XR-ODT for ADHD

The FDA has given the green light to Adzenys XR-ODT (Neos Therapeutics) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in patients 6 years of age and older. With this approval, the product is the first extended-release orally disintegrating tablet (ODT) for this indication.

Adzenys XR-ODT contains amphetamine loaded onto a mixture of immediate-release and polymer-coated, delayed-release resin particles. The treatment is patent-protected and is not a generic version of mixed amphetamine salts extended-release (MAS-XR) capsules.

The clinical program demonstrated that Adzenys XR-ODT is bioequivalent to a previously approved MAS-XR capsule (Adderall XR, Shire), one of the most commonly prescribed medications for the treatment of patients with ADHD. Adzenys XR-ODT will be available in six dosage strengths equivalent to the Adder-all XR dosage strengths.

Source: Neos Therapeutics, January 27, 2016

Generic Approvals

Adapalene Topical Solution

Call Inc. (doing business as Rochester Pharmaceuticals) has received FDA approval to market the first generic adapalene topical solution (swabs), 0.1%. The drug, a retinoid, is prescribed for the topical treatment of acne vulgaris. Topical adapalene was initially approved by the FDA in 1996 under the brand name Differin (Galderma).

Sources: FDA, January 5, 2016, and DailyMed

Naftifine Hydrochloride Cream

The FDA has approved the application of Taro Pharmaceuticals USA, Inc., to market naftifine hydrochloride cream USP, 2%, the generic version of Naftin cream (Merz Pharmaceuticals). Naftifine hydrochloride cream is an allylamine antifungal indicated for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organism Trichophyton rubrum.

Sources: FDA, January 6, 2016, and Naftin cream prescribing information

Deferasirox Tablets for Oral Suspension

Actavis Elizabeth, LLC, has been approved by the FDA to market the first generic deferasirox tablets for oral suspension. The drug is prescribed for the treatment of chronic iron overload in patients 2 years of age and older due to blood transfusions and in patients 10 years of age or older due to non–transfusion-dependent thalassemia syndromes. Deferasirox is an iron chelator that works by attaching to iron in the body, which is then excreted in feces. The drug, originally marketed as Exjade (Novartis), is available in 125-mg, 250-mg, and 500-mg tablets.

Sources: FDA, January 26, 2016, and Exjade prescribing information

Milnacipran Hydrochloride Tablets

The FDA has granted approval to Liberty Pharma, Inc., to market milnacipran hydrochloride tablets. This selective serotonin and norepinephrine reuptake inhibitor is prescribed for the management of fibromyalgia. Patients who took the drug in clinical studies experienced at least a 30% reduction in pain from baseline. It is available in 12.5-mg, 25-mg, 50-mg, and 100-mg strengths. It was originally marketed as Savella (Cypress Bioscience); this is the first generic version of the drug.

Sources: FDA, January 27, 2016, and Savella prescribing information

NEW INDICATIONS

Opdivo/Yervoy Combination For Metastatic Melanoma

The FDA has approved nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the treatment of patients with BRAF V600 wild-type and BRAF V600 mutation-positive unresectable or metastatic melanoma. Both drugs are marketed by Bristol-Myers Squibb.

This approval expands the original indication for the nivolumab/ipilimumab regimen for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma to include patients regardless of BRAF mutational status, based on data from the phase 3 Check-Mate-067 trial, in which progression-free survival and overall survival were coprimary endpoints.

The FDA also expanded the use of nivolumab as a single agent to include patients with previously untreated BRAF mutation-positive advanced melanoma. Nivolumab was approved by the FDA in November 2015 for use in previously untreated patients with BRAF V600 wild-type unresectable or metastatic melanoma.

Source: Bristol-Myers Squibb, January 23, 2016

Kyprolis Combo Therapies For Multiple Myeloma

The FDA has approved the supplemental new drug application for carfilzomib (Kyprolis, Amgen) for injection in combination with dexamethasone or with lenalidomide (Revlimid, Celgene) plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. The FDA also approved carfilzomib as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. This decision converts to full approval the initial accelerated approval that carfilzomib received in July 2012 as a single agent.

In July 2015, the FDA approved another expanded indication for carfilzomib in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior lines of therapy.

Source: Amgen, January 21, 2016

Fosaprepitant for Nausea, Vomiting Linked With MEC

The FDA has approved a supplemental new drug application for intravenous (IV), single-dose fosaprepitant dimeglumine (Emend, Merck), a substance P/neurokinin-1 (NK1) receptor antagonist, in combination with other antiemetic medications, for the prevention of delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC).

With the new approval, fosaprepitant for injection is the first IV, single-dose NK1 receptor antagonist approved in the U.S. for both highly emetogenic chemotherapy and MEC.

Fosaprepitant dimeglumine for injection is an IV prodrug of aprepitant, the oral formulation of Emend. When administered by injection, fosaprepitant is rapidly converted in the body to aprepitant, which is a selective high-affinity antagonist of human substance P/NK1 receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors––the targets of current therapies for chemotherapy-induced nausea and vomiting.

Source: Merck, February 4, 2016

Botox for Lower Limb Spasticity

The FDA has approved Botox (ona-botulinumtoxinA, Allergan) for the treatment of lower limb spasticity in adults to reduce the severity of increased stiffness in ankle and toe muscles. Botox is the only botulinum toxin product cleared by the FDA for the treatment of multiple muscle groups of the upper (elbow, wrist, fingers, and thumb) and lower limbs that may be affected by spasticity.

Botox was first approved for the treatment of upper limb spasticity (ULS), or increased muscle stiffness in the elbow, wrist, and fingers, in adults in March 2010. Additional FDA approval was received in April 2015 to expand the Botox label for the treatment of adults with ULS to include the addition of two thumb muscles.

Source: Allergan, January 22, 2016

Arzerra for CLL

The FDA has approved ofatumumab (Arzerra, Novartis) for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL). Ofatumumab was previously approved for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy was considered inappropriate and for patients with CLL that was refractory to fludarabine and alemtuzumab.

The new approval was based on the demonstration of improved progression-free survival in a randomized, open-label trial comparing ofatumumab with observation in patients whose disease had a complete or partial response after at least two lines of prior therapy.

Source: FDA, January 19, 2016

Cosentyx for Arthropathies

The FDA has approved secukinumab (Cosentyx, Novartis) for two new indications: the treatment of adult patients with active ankylosing spondylitis (AS) and active psoriatic arthritis (PsA). With these new approvals, Cosentyx is now the first interleukin-17A antagonist approved for AS as well as for moderate-to-severe plaque psoriasis and PsA, which affects as many as 30% of patients with psoriasis. Secukinumab was originally approved for adult patients with moderate-to-severe plaque psoriasis in January 2015.

Source: Novartis, January 15, 2016

NEW FORMULATIONS

Dexilant Soluble Tablets for GERD-Associated Heartburn

The FDA has approved Dexilant Solu-Tab delayed-release orally disintegrating tablets (Takeda Pharmaceuticals U.S.A.), a new formulation of dexlansoprazole that can be taken by allowing the tablet to melt in the patient’s mouth. The product is a proton pump inhibitor indicated for the treatment of heartburn associated with symptomatic nonerosive gastroesophageal reflux disease (GERD) and for the maintenance of healed erosive esophagitis (EE) and the relief of heartburn in adults 18 years of age and older.

In addition to Dexilant SoluTab, dexlansoprazole is available as a capsule, which is indicated for heartburn associated with symptomatic nonerosive GERD, the healing of EE, and the maintenance of healed EE in adults.

Source: Takeda Pharmaceuticals U.S.A., January 27, 2016

Single-Dose Dalvance for ABSSSIs

The FDA has approved a supplemental new drug application (sNDA) to update the label for dalbavancin (Dalvance, Allergan) for injection. The expanded label will include a single dose administered as a 30-minute intravenous infusion of dalbavancin for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) caused by designated susceptible gram-positive bacteria in adults, including infections caused by methicillin-resistant Staphylococcus aureus (MRSA).

The sNDA was based on results from a phase 3 study that compared a single 1,500-mg dose of dalbavancin with the two-dose regimen of 1,000 mg followed one week later by 500 mg.

Dalbavancin is a second-generation, semisynthetic lipoglycopeptide that consists of a lipophilic side-chain added to an enhanced glycopeptide backbone. The compound has demonstrated bactericidal activity in vitro against a range of gram-positive bacteria, such as S. aureus (including MRSA strains) and Streptococcus pyogenes, as well as certain other streptococcal species.

Source: Allergan, January 21, 2016

5-mg Gleostine for Chemotherapy

Lomustine (Gleostine, NextSource Biotechnology) 5-mg capsules have been approved by the FDA and are now commercially available in the U.S. Lomustine is approved for use as a single-agent treatment or in combination with other approved chemotherapeutic agents. The product is indicated to treat both primary and metastatic brain tumors as well as Hodgkin’s disease. The new approval adds a fourth dosage strength to the lomustine product lineup, which now includes 5-mg, 10-mg, 40-mg, and 100-mg strengths.

Source: NextSource Biotechnology, January 20, 2016

FDA REVIEW ACTIVITIES

Advisory Committee Vote

Brintellix Backed for Cognitive MDD

The FDA’s Psychopharmacologic Drugs Advisory Committee voted 8 to 2 that substantial evidence had been presented to support the efficacy of vortioxetine (Brintellix, Takeda/Lundbeck) for treating certain aspects of cognitive dysfunction in adults with major depressive disorder (MDD). The committee also discussed whether cognitive dysfunction in MDD represents an appropriate target for drug development.

The panel’s input will be considered by the agency in its review of the vortioxetine supplemental new drug application, which was accepted for review in August 2015. The FDA is expected to make its approval decision by March 28, 2016. Vortioxetine was approved for the treatment of MDD in adults in September 2013.

Source: Lundbeck, February 4, 2016

Fast-Track Designations

Ryanodex for Exertional Heat Stroke

The FDA has granted fast-track status to dantrolene sodium (Ryanodex, Eagle Pharmaceuticals) injectable suspension for the treatment of exertional heat stroke, a rare, sudden, and unpredictable disorder that may result in severe multiorgan dysfunction and death. No FDA-approved treatment is available.

Dantrolene sodium, a skeletal-muscle relaxant, is indicated for the treatment of malignant hyperthermia (MH) in conjunction with appropriate supportive measures, and for the prevention of MH in patients at high risk.

Source: Eagle Pharmaceuticals, February 1, 2016

IMC-1 for Fibromyalgia

The FDA has granted a fast-track designation to IMC-1 (Innovative Med Concepts) for the treatment of fibromyalgia. The product is a fixed-dose combination of famciclovir, an antiviral nucleoside analogue, and celecoxib, a cyclooxygenase-2 inhibitor.

A phase 2, randomized, double-blind, placebo-controlled trial of IMC-1 in patients with fibromyalgia has been completed. The study was designed to confirm the hypothesis that latent herpes virus may have a role in fibromyalgia symptoms or recurrence. The suppression of chronic tissue-resident herpes virus––the mechanism of action of IMC-1––is expected to improve fibromyalgia-related symptoms.

Source: Innovative Med Concepts, January 29, 2016

Priority Review Designations

Bezlotoxumab for C. Difficile

The FDA has accepted for review the biologics license application for bezlotoxumab (Merck), an investigational antitoxin for the prevention of Clostridium difficile infection recurrence. The FDA granted priority review for bezlotoxumab, with a Prescription Drug User Fee Act action date of July 23, 2016.

Bezlotoxumab is an investigational antitoxin given in conjunction with standard of care antibiotics that are used in the treatment of C. difficile infection. It is not an antibiotic. Bezlotoxumab is designed to neutralize C. difficile toxin B, a toxin that can damage the gut wall and cause inflammation, leading to C. difficile-associated diarrhea.

Source: Merck, January 27, 2016

Venetoclax for Chronic CLL

The FDA has accepted a new drug application (NDA) for venetoclax (Genentech/AbbVie/Roche) with priority review status as a potential treatment for patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, including those with the 17p deletion.

Venetoclax is a small-molecule inhibitor of the B-cell lymphoma-2 (BCL-2) protein. In April 2015, the FDA granted breakthrough therapy status to single-agent venetoclax for the treatment of relapsed/refractory CLL (R/R CLL) in previously treated patients with the 17p deletion. In January 2016, the FDA added a breakthrough therapy designation for venetoclax in combination with rituximab for the treatment of patients with R/R CLL.

The new NDA was partly based on results from an open-label, single-arm, phase 2 study in patients with R/R CLL or previously untreated CLL with the 17p deletion. In that trial, the overall response rate was 79% among 107 patients with R/R CLL treated with venetoclax. In addition, 8% of patients achieved a complete response with or without complete recovery of blood counts in the bone marrow.

Sources: Genentech, January 12, 2016; and AbbVie, January 28, 2016

Breakthrough Therapy Status

Rapastinel for MDD

The investigational medication rapastinel (GLYX-13, Allergan) has received a breakthrough therapy designation from the FDA for adjunctive treatment of major depressive disorder (MDD). This follows the fast-track designation for rapastinel granted by the FDA in 2014.

Rapastinel is an intravenous formulation of a new N-methyl-D-aspartate receptor partial agonist. The treatment has shown a rapid onset of antidepressant efficacy one day after a single dose in a phase 2 clinical trial of patients with MDD who had experienced an inadequate response to one or more antidepressants. No psychotomimetic or hallucinogenic adverse effects were observed with rapastinel. Phase 3 registration trials are expected to begin in 2016.

Source: Allergan, January 29, 2016

Lynparza for Prostate Cancer

The FDA has granted breakthrough therapy status to olaparib (Lynparza, AstraZeneca), a first-in-class oral poly(ADP-ribose) polymerase inhibitor, for single-agent therapy of BRCA1/2 or ATM gene-mutated metastatic castration-resistant prostate cancer (mCRPC) in patients who have received a prior taxane-based chemotherapy and at least one newer hormonal agent (abiraterone or enzalutamide).

The FDA’s decision was based on results from the phase 2 TOPARP-A trial, which indicated that olaparib monotherapy in patients with mCRPC may offer substantial improvement over available treatments for the biomarker-selected population with this life-threatening condition.

Source: AstraZeneca, January 28, 2016

Venetoclax for AML

The FDA has granted breakthrough therapy status to the investigational agent venetoclax (AbbVie/Genentech/Roche) in combination with hypomethylating agents for the treatment of patients with untreated acute myeloid leukemia (AML) who are ineligible to receive standard induction therapy (high-dose chemotherapy).

Source: AbbVie, January 28, 2016

Complete Response Letters

Kalydeco for Cystic Fibrosis

Vertex Pharmaceuticals has received a complete response letter from the FDA in response to the company’s supplemental new drug application for the use of ivacaftor (Kalydeco) in patients 2 years of age and older with cystic fibrosis (CF) who have one of 23 residual function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The FDA determined that it cannot approve the application in its present form.

Ivacaftor, which received a breakthrough therapy designation from the FDA in 2013, is approved in the U.S. to treat patients 2 years of age and older who have one of 10 mutations in the CFTR gene (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H). The treatment is not currently indicated for patients with CF due to other CFTR gene mutations.

Source: Vertex Pharmaceuticals, February 5, 2016

MCNA for Bladder Cancer

The FDA has issued a complete response letter to the biologics license application for MCNA (Telesta Therapeutics). In its letter, the FDA stated that an additional phase 3 clinical trial would be necessary to establish adequately the treatment’s efficacy and safety. The FDA also encouraged Telesta Therapeutics to meet with it to discuss further clinical development of MCNA.

MCNA is a biologic therapy developed to provide a therapeutic alternative to surgery for high-risk patients with non– muscle-invasive bladder cancer who are refractory to or relapsing from first-line therapy with bacillus Calmette–Guérin. MCNA is derived from the cell wall fractionation of a nonpathogenic bacterium. Its activity is believed to be through a dual mechanism of immune stimulation and direct anticancer effects.

Source: Telesta Therapeutics, February 2, 2016

Kyndrisa for Duchenne Muscular Dystrophy

The FDA has issued a complete response letter to the new drug application for drisapersen (Kyndrisa, BioMarin Pharmaceutical Inc.) for the treatment of patients with Duchenne muscular dystrophy amenable to exon 51 skipping. The agency concluded that the standard of substantial evidence of effectiveness had not been met.

Drisapersen is an antisense oligonucleotide that induces exon skipping to provide a molecular patch for dystrophin transcripts produced by certain mutated dystrophin genes. Exons are the parts of a gene that contain the instructions for generating a protein. In applicable cases, skipping an exon near the mutation allows the production of a truncated but functional dystrophin protein.

Source: Biomarin Pharmaceutical Inc., January 14, 2016

New Applications

SB-318 for Mucopolysaccharidosis

The FDA has cleared an investigational new drug application for SB-318 (Sangamo BioSciences), a single-treatment strategy intended to provide a life-long therapy for patients with mucopolysaccharidosis type I (MPS I). The approval allows Sangamo to initiate a phase 1/2 clinical study designed to assess the safety, tolerability, and potential efficacy of SB-318 in adults with varying severities of MPS I.

SB-318 is an in vivo genome-editing application based on the company’s proprietary In Vivo Protein Replacement Platform, a single-treatment strategy designed to produce stable circulating levels of a therapeutic protein from a patient’s liver for the lifetime of the individual. SB-318 treatment is intended to eliminate the need for enzyme replacement therapy (ERT), which is the current standard of care for most patients with MPS I. ERT for MPS I often requires weekly infusions of a recombinant form of the enzyme alpha-L-iduronidase (IDUA), which is missing or defective in patients with the disorder. While the infusions take several hours, circulating levels of IDUA are undetectable within hours of the treatment because of the replacement protein’s short half-life.

Source: Sangamo BioSciences, February 8, 2016

IV Immunoglobulin

The FDA has accepted for review a biologics license application for IVIG-SN (human normal immunoglobulin G for intravenous administration, Green Cross Corporation) intended for the treatment of primary immunodeficiency diseases (PIDs). The Prescription Drug User Fee Act date has been scheduled for the fourth quarter of 2016. IVIG-SN demonstrated positive results in a phase 3 study in patients with PIDs, meeting its primary endpoint of no acute serious bacterial infections.

Source: Green Cross Corporation, January 25, 2016

Humira Biosimilar

The FDA has accepted for review a biologics license application for ABP 501 (Amgen), a biosimilar candidate to adalimumab (Humira, AbbVie). The agency set a Biosimilar User Fee Act target action date of September 25, 2016.

The active ingredient in ABP 501 is an anti–tumor necrosis factor alpha monoclonal antibody that has the same amino acid sequence as adalimumab. ABP 501 also has the same pharmaceutical dosage form and strength as adalimumab.

Source: Amgen, January 25, 2016

Jardiance CV Outcomes Data

The FDA has accepted a supplemental new drug application for empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) based on cardiovascular (CV) risk-reduction data from the landmark EMPA-REG OUTCOME trial.

Over a median period of 3.1 years, empagliflozin significantly reduced the risk of CV death, nonfatal heart attack, or nonfatal stroke by 14% compared with placebo. The risk of CV death was reduced by 38%, with no significant difference in the risk of nonfatal heart attack or nonfatal stroke. Treatment with empagliflozin also resulted in a 32% reduction in all-cause mortality and a 35% reduction in hospitalization for heart failure.

Empagliflozin was approved by the FDA in August 2014 as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes.

Source: Eli Lilly, January 25, 2016

AP32788 for Lung Cancer

The FDA has completed its review of the investigational new drug application for AP32788 (Ariad Pharmaceuticals), a tyrosine kinase inhibitor designed as a targeted therapy for patients with non– small-cell lung cancer with specific mutations in epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) genes. A phase 1/2 clinical trial is expected to begin in the second quarter of 2016.

AP32788 targets tumors driven by EGFR or HER2 kinases and was designed to achieve selective inhibition of exon 20 insertion mutations in these kinases. In preclinical studies, AP32788 inhibited EGFR mutations, including exon 20 mutations, while remaining selective for native EGFR. It was also active against HER2-activating mutations, including exon 20 mutations.

Source: Ariad Pharmaceuticals, February 2, 2016

Generic Advair Diskus

Mylan N.V. has submitted an abbreviated new drug application for fluticasone propionate 100, 250, and 500 mcg and salmeterol 50 mcg inhalation powder to the FDA. This product is the generic version of Advair Diskus (GlaxoSmithKline), which is indicated for the treatment of asthma and for the maintenance treatment of airflow obstruction and the reduction of exacerbations in patients with chronic obstructive pulmonary disease.

If the product is approved under the FDA’s standard six-month review period, a generic version of Advair that may be routinely substituted for GlaxoSmith-Kline’s medication could be launched in 2017, analysts believe.

Novartis’ Sandoz unit is also working on a generic copy of Advair, and the arrival of such cut-price versions is likely to add to price pressures on other respiratory products, such as Symbicort (budesonide/formoterol, AstraZeneca), according to a Reuters report.

Sources: Mylan N.V., January 11, 2016, and Reuters, January 12, 2016

CLINICAL TRIAL NEWS

Blincyto Improves Leukemia OS

A prespecified interim analysis has shown that the primary endpoint of improved overall survival (OS) was met in the phase 3 TOWER trial. This randomized, open-label study evaluated the efficacy of the antibody construct blinatumomab (Blincyto, Amgen) compared with standard-of-care chemotherapy in adult patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia. The study’s independent data monitoring committee recommended, and Amgen agreed, that the study should end early for efficacy.

Blinatumomab is a bispecific CD19-directed CD3 T-cell engager antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and to CD3 expressed on the surface of T cells (lymphocytes capable of killing other cells perceived as threats).

Source: Amgen, February 4, 2016

Cabozantinib Tops Everolimus For OS in Kidney Cancer

Positive overall survival (OS) results have been reported from the pivotal phase 3 METEOR trial, which compared cabozantinib (Cometriq, Exelixis, Inc.) with everolimus (Afinitor, Novartis) in 658 patients with advanced renal cell carcinoma who had experienced disease progression after treatment with a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor. In an interim analysis for OS, a secondary endpoint, the results showed a statistically significant increase in OS for patients treated with cabozantinib compared with those treated with everolimus (20 months versus 15 months, respectively; P = 0.005).

Cabozantinib inhibits the activity of tyrosine kinases, including MET, VEGF receptors, AXL, and RET. These receptor tyrosine kinases are involved in both normal cellular function and pathological processes, such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.

Source: Exelixis, Inc., February 1, 2016

Chlorthalidone Beats HCTZ in BP

Low-dose chlorthalidone reduced ambulatory blood pressure (ABP) in patients with stage-1 hypertension, whereas low-dose hydrochlorothiazide (HCTZ) resulted in masked hypertension, according to a study published in the Journal of the American College of Cardiology (JACC). The researchers found that chlorthalidone, but not HCTZ, provided significant reductions in systolic and diastolic 24-hour ABP and nighttime BP at weeks 4 and 12 (P < 0.01). Nighttime systolic ABP was significantly lower with chlorthalidone compared with HCTZ at weeks 4 (P = 0.015) and 12 (P = 0.020). HCTZ therapy converted sustained hypertension into masked hypertension.

Source: JACC, January 28, 2016

Strada Fails Depression Trial

Strada (MSI-195, MSI Methylation Sciences) failed to demonstrate efficacy over placebo in a phase 2 clinical trial designed to evaluate the drug’s efficacy and safety when added to ongoing antidepressant therapy in patients with major depressive disorder (MDD) who have had an inadequate response to current antidepressant treatment.

The HORIZON trial was a U.S., double-blind, randomized, placebo-controlled add-on study investigating the ability of Strada plus current antidepressant therapy to reduce depressive symptoms based on the Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale in MDD patients who have had an inadequate response to current antidepressant therapy. The trial focused on MDD patients who had failed to respond to antidepressant therapy for at least six weeks. The trial was designed to measure safety and efficacy over an eight-week period.

Source: MSI Methylation Sciences, January 27, 2016

Gilotrif Bests Iressa in NSCLC

Positive results have been announced from the LUX-Lung 7 trial. Superiority in progression-free survival and time to treatment failure was demonstrated with the second-generation epidermal growth factor receptor (EGFR)-directed therapy afatinib (Gilotrif, Boehringer Ingelheim) compared with first-generation gefitinib (Iressa, AstraZeneca) in the first-line treatment of patients with advanced non–small-cell lung cancer with common EGFR mutations (del19 or L858R). The results showed that afatinib significantly reduced the risk of lung cancer progression by 27% compared with gefitinib.

Source: Boehringer Ingelheim, January 27, 2016

FDA Puts Full Clinical Hold On Pacritinib Trials

Due to patient deaths attributed to intercranial hemorrhage, cardiac failure, and cardiac arrest, the FDA has placed a full clinical hold on studies being conducted for pacritinib (CTI BioPharma Corp.), which was being evaluated in a phase 3 program (PERSIST-2) for the treatment of patients with myelofibrosis. Under the full clinical hold, all patients currently receiving pacritinib must discontinue treatment immediately, and no patients can be enrolled in a pacritinib trial or start pacritinib as initial or crossover treatment.

The FDA has recommended that CTI BioPharma Corp. conduct dose-exploration studies for pacritinib in patients with myelofibrosis; submit final study reports and data sets for PERSIST-1 and PERSIST-2; provide certain notifications; revise relevant statements in the related investigator’s brochure and informed consent documents; and make certain modifications to study protocols. CTI Bio-Pharma Corp. has withdrawn its investigational new drug application for the drug until it can review the safety and efficacy data generated by the phase 3 PERSIST-2 trial and decide how to proceed.

Sources: BioSpace, February 10, 2016, and CTI BioPharma Corp.

Opdivo Meets Endpoint For Head and Neck Cancer

According to Bristol-Myers Squibb, its phase 3, open-label CheckMate-141 trial evaluating nivolumab (Opdivo) versus the investigators’ choice of therapy in patients with recurrent or metastatic platinum-refractory squamous-cell carcinoma of the head and neck was stopped early because the study had met its primary endpoint (overall survival). Patients who received nivolumab demonstrated superior overall survival compared with the control arm.

Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor currently indicated for the treatment of BRAF V600 wild-type or BRAF V600 mutation-positive unresectable or metastatic melanoma, advanced renal cell carcinoma, and metastatic non–small-cell lung cancer with progression during or after platinum-based chemotherapy.

Source: Bristol-Myers Squibb, January 28, 2016

Jakafi/Stivarga for Colorectal Cancer

Incyte Corporation announced that it had stopped a phase 2 study of ruxolitinib (Jakafi) or placebo in combination with regorafenib (Stivarga, BayerHealthcare) in patients with relapsed or refractory metastatic colorectal cancer and high C-reactive protein (CRP). The decision to halt the study was made after a planned interim analysis of the high-CRP subgroup demonstrated that ruxolitinib plus regorafenib did not show a sufficient level of efficacy to warrant continuation.

Ruxolitinib is a first-in-class Janus kinase 1 (JAK1)/JAK2 inhibitor approved by the FDA for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. Ruxolitinib is also indicated for the treatment of patients with intermediate- or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF.

Source: Incyte Corporation, January 27, 2016

DRUG SAFETY ISSUE

Chinese-Made Cough Syrup Contains Morphine

The FDA is warning consumers not to use Licorice Coughing Liquid, a cough syrup product sold over the counter, because it contains unidentified morphine. The cough syrup’s labeling contains information written in English and Chinese. The product labeling does not identify the presence of morphine in English. Consumers who are hypersensitive to morphine could suffer severe allergic reactions if they take this product, the FDA says. Other effects of morphine can include, but are not limited to, respiratory depression and death.

The product is manufactured by Ma Ying Long Pharmaceutical Group in China and is distributed in the U.S. by Master Herbs USA, Inc., in Pomona, California. The distributor has agreed to recall the product, which is available online and in some retail stores.

Source: FDA, January 16, 2016

RESEARCH BRIEFS

When Does Hip Pain Mean Osteoarthritis?

Although a mention of hip pain usually triggers a physical exam followed by an x-ray, many cases of hip osteoarthritis in older people might be missed if their practitioners rely on hip radiographs, say researchers from Boston University, University of California, Tufts Medical Center, and other institutions. Their study found that most patients with frequent hip pain did not have radiographic hip osteoarthritis, and that most patients with radiographic hip osteoarthritis did not have frequent hip pain.

The researchers analyzed data from pelvic radiographs in two groups: the Framingham Osteoarthritis Study and the Osteoarthritis Initiative.

Only 16% of 946 patients with frequent hip pain in the Framingham study had radiographic evidence of hip osteoarthritis; 21% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of x-ray for hip pain localized to the groin was 37% (specificity 91%, positive predictive value 6%, negative predictive value 99%).

Among the 4,366 Osteoarthritis Initiative patients, only 9% of those with painful hips showed x-ray evidence of osteoarthritis, and 24% of those with radiographic evidence of osteoarthritis were painful. The sensitivity was 17% (specificity 94%, positive predictive value 7%, negative predictive value 98%).

Factoring in painful internal rotation did not change the outcomes.

The researchers note that inadequate recognition of osteoarthritis has consequences in older patients, such as increased morbidity from heart disease, lung disease, diabetes, and frailty. Health professionals should continue with the evaluation and treatment of osteoarthritis, they conclude, despite negative radiographic findings.

Source: BMJ, December 2015

Smoking Raises Heart, Lung Risks in HIV

People infected with the human immunodeficiency virus (HIV) are twice as likely to smoke as the general population (42% versus 21%), say researchers from the University of Modena, Italy, and they’re less likely to quit smoking. But these patients are also nearly four times more likely to have lung cancer, many times more likely to have chronic obstructive pulmonary disease (COPD), and their risk of cardiovascular disease goes up by 76%.

Antiretroviral therapy, immune hyperactivation, and premature senescence have been implicated in the pathogenesis of lung and cardiovascular disease in HIV patients, the researchers say. The researchers sought to determine the relationship of lifetime smoking history and risk of heart and lung disease in HIV patients.

In their study of 903 clinic patients with HIV, 214 (24%) never smoked, 259 (29%) were former smokers, and 430 (48%) were current smokers. The researchers further divided the groups according to number of years smoked and time since quitting smoking.

Current smokers had a median of 22.5 pack-years of smoking versus 14 pack-years for former smokers. Lifetime cumulative smoking exposure was a “significant and powerful predictor” of cardiopulmonary disease. The study found a trend toward higher prevalence of clinical and subclinical lung and heart disease, as well as multimorbidity (at least two lung abnormalities and one heart abnormality), with increasing pack-years. The highest prevalence was among current smokers.

Three patients developed lung cancer. Of 350 who had pulmonary function testing, 40 were diagnosed with COPD. Among patients without clinical COPD and/or lung cancer, computed tomography scanning identified emphysema, bronchiolitis, noncalcified lung nodules, significant bronchial wall thickening, and bronchiectasis. Nearly half of the patients had multimorbidity lung disease. Five percent had evidence of prior myocardial infarction.

Smoking cessation that occurred less than five years ago among patients with more than 10 pack-years was a significant risk factor for multimorbidity heart and lung disease.

The researchers say current smoking status is a poor indicator of the risk of heart and lung disease among these patients. When assessing, they suggest, estimate the pack-year history for both former and current smokers, which could help with cost-effective screening.

Source: PLOS One, December 2015

Swallowing After Cardiac Surgery With Intubation

Many patients have trouble swallowing after cardiac surgery, due to older age, stroke, surgical procedures, and other factors. University of Auckland researchers say the odds of dysphagia multiply with longer intubation, rising to 67% prevalence with more than 48 hours of intubation. They also note that dysphagia after cardiac surgery is associated with poor prognosis and higher risks of complications, such as aspiration.

Aspiration has been linked to a higher rate of pneumonia in general medical patients. One study found patients who aspirated had 10 times the risk of pneumonia; those with silent aspiration (lacking the cough reflex) had 13 times the risk.

In the current study, the researchers looked at data from 190 patients who underwent cardiac surgery and were intubated for 48 hours or more.

Only 41 patients (22%) were referred to speech-language pathology for a swallowing assessment, but 33 were diagnosed with dysphagia. Pneumonia was three times more likely with a dysphagia diagnosis. Stroke patients were seven times more likely to be diagnosed with dysphagia. More than half of patients with dysphagia had had a tracheostomy.

Twenty-four of the 33 patients with dysphagia were given instrumental assessments (including fiber-optic endoscopic evaluation of swallowing [FEES]); 17 (70%) were identified as having silent aspiration. The researchers say the number was probably “far greater” because so few were referred to speech-language pathology, and only 13% received an instrumental assessment. All patients who had pneumonia and received an instrumental assessment were silent aspirators.

This was a retrospective study. On their cardiac unit, the researchers say, there was no standard protocol for dysphagia screening or referral to speech-language pathology when the study patients had surgery. Noting that early referral is important, they point to studies that have also shown dysphagia screens by nurses, clinical pathways on swallowing, and a speech-language pathologist-led FEES service have all improved outcomes.

Source: Journal of Critical Care, February 2016

How Stereotypes Hurt Health Care

Patients usually know—or at least suspect—when they’re being stereotyped, for their lifestyle, say, or ethnic background. Researchers from the University of Southern California, Loyola Marymount University, and the University of Michigan say that kind of stereotyping contributes to health disparities. They point to research, for instance, that suggests patients may respond to a “heath care stereotype threat” (HCST) by underusing or even avoiding health care.

To find out what effect stereotyping might have on the patient’s—and the practitioner’s—health care interaction, the researchers asked 1,479 participants in the 2012 Health and Retirement Study three questions. First, “When you visit the doctor, do you worry that the doctor or other medical staff makes judgments about you because of your [race/ethnic background, gender, age, weight, money]?” Those who reported HCST were then asked if they worried that they might act in ways that justify such judgments and whether they thought that the judgments affected the quality of health care they received.

In all, 17% of participants reported some degree of HCST related to ethnicity/race and gender, but also weight, socioeconomic status, and perceived intelligence. Patients who said they felt one or more types of HCST reported higher average physician distrust. Those who reported two or more types of HCST were more likely to be dissatisfied with health care, compared with respondents who reported no threat.

Patients who reported two or more types of HCST were nearly four times more likely to report worrying that they acted in ways that justified health care practitioners’ judgments and eight times more likely to think that the judgments affected the quality of care they received.

Moreover, patients who said they had experienced one or more types of HCST were likely to have poorer global physical and mental health, as indicated by self-rated health, diagnosed hypertension, and depressive symptoms.

Cues that signify that doctors’ offices and hospitals are “identity safe,” such as visible nondiscrimination policies, may help reduce the incidence of HCST, the researchers say. They also cite research that has found that providing information about potential “stereotype threat” to susceptible individuals can help them deal with and combat it.

Source: American Journal of Preventive Medicine, February 2016

Is Moderate Drinking Healthy? The Debate Continues

How much alcohol is harmful, and is some actually beneficial? The debate goes on. Now, researchers from McGill University and Royal Liverpool University say findings from the “substantial body of literature” that suggest health benefits from moderate alcohol intake may have been based on residual confounding, which is the distortion that remains after controlling for confounding in the design and/or analysis of a study.

The researchers analyzed data on 24,029 participants in the Health and Retirement Study. They measured participants’ drinking level based on weekly alcohol consumption, as reported at three interviews in the four years before baseline. Occasional drinkers—people who reported drinking on at least one occasion but always less than once a week—were used as the reference point. Those who reported drinking at least one drink per week on at least one occasion were categorized as “regular drinkers,” and further classified according to the average number of drinks per week.

The researchers included sociodemographic variables in their analysis, such as age, gender, income, and religiosity; and health-related variables, such as smoking, body mass index, binge drinking, and exercise. They also factored in variables such as whether participants had pain, chronic diseases, psychiatric disorders, or impaired cognitive function.

During the 206,966 person-years of follow-up, 7,902 people died. When fully controlling for bias, the researchers found no association between moderate alcohol use and reduced mortality. In fact, no level of regular alcohol consumption was associated with reduced mortality. Even drinking more than 21 drinks a week had a hazard ratio (HR) of 1.45.

The fully adjusted HR for nondrinkers, compared with occasional drinkers, was 1.19. The finding of increased mortality in abstainers relative to occasional drinkers, despite “extensive adjustment for confounders,” suggests that residual confounding plays a significant role in explaining the apparent health benefits of alcohol consumption, the researchers say, “given the physiologic implausibility that drinking less than one drink per week could reduce all-cause mortality by 19%.”

Source: American Journal of Medicine, February 2016

False Estradiol Results From Fulvestrant Interaction

Estradiol testing may guide treatment for patients with estrogen receptor-positive breast cancer, but researchers from Rush University Medical Center in Chicago have a cautionary report about relying on that when fulvestrant, an estrogen receptor antagonist, is used with standard steroid immunoassays. They report on a patient who had a falsely elevated estradiol reading that led to unnecessary procedures.

Their patient underwent a bilateral oophorectomy and was then started on antiestrogen therapy with letrozole and fulvestrant, as well as zoledronic acid. At her request, her primary oncologist obtained a serum estradiol level, which was “unexpectedly” high. The finding was puzzling, the authors say, because she had reported menopausal symptoms, such as hot flashes, which was not consistent with the estradiol level obtained. She also had a complete clinical response to treatment, according to symptoms, radiological findings, and decreasing levels of carcinoma antigen 125.

A pelvic ultrasound revealed a possible small soft tissue density in the left adnexal region—a “concerning” finding suggesting ovarian remnant syndrome, a rare condition in which ovarian tissue remains after oophorectomy. After additional imaging and laparoscopy, pathology revealed fibrovascular and adipose tissue but no ovarian tissue, ruling out ovarian remnant syndrome as the cause of the elevated estradiol.

Endocrinologists suspected that fulvestrant, which has a molecular structure similar to that of estradiol, was cross-reacting with the standard estradiol immunoassay. That theory was confirmed by testing the serum estradiol levels with the more sensitive and specific liquid chromatography-tandem mass spectrometry, which showed that the levels were actually undetectable.

Fulvestrant has no known agonist effects; it has not previously been reported to elevate estradiol levels or cross-react with estradiol immunoassays, the authors say. Neither the package insert for fulvestrant nor the product insert for the immunoassay warn about the interaction. The authors advise clinicians to be aware of the “high likelihood” of this potential drug–assay interaction.

Source: Clinical Breast Cancer, February 2016

Method for Rapid Detection Of Infection in Wounds

A new method for detecting infection in wounds could take physicians less than one minute to complete rather than the current 24 hours it takes to “plate” bacteria and leave them to incubate overnight, according to research from George Washington University’s School of Medicine and Health Sciences that was published in Wound Repair and Regeneration.

Victoria Shanmugam, MD, and her colleagues tested an inexpensive, disposable electrochemical sensor that immediately reveals the presence of bacteria in chronic wounds based on the detection of pyocyanin, a bacterial quorum-sensing molecule produced by Pseudomonas bacteria. The probe correctly identified the presence of bacteria 71% of the time and the absence of bacteria 57% of the time.

“Being able to detect Pseudomonas and other infectious organisms at the time of the clinic visit will greatly enhance our ability to take care of patients,” Dr. Shanmugam said. “We would not have to wait for culture results before making a decision about antibiotics, and this would allow us to better tailor therapies for our patients.”

After further enhancement and testing, probes harnessing this method could potentially provide a way for physicians to detect wound infections at bedside, allowing physicians to switch from broad-spectrum antibiotics to specific directed therapies sooner, thereby lowering health care costs, minimizing drug resistance, and improving patient care outcomes, according to Dr. Shanmugam.

“Infections are a major challenge in medicine, and by using this probe, we were able to harness one of the unique molecules produced by bacteria to detect infection,” she said. “We plan to continue to refine this testing method and hope to scale it up for detection of other bacteria and to optimize it for clinical use.”

Source: GW School of Medicine and Health Sciences, February 5, 2016

Infrared Light Used To Measure Blood Glucose

Researchers in Japan have developed a new method for measuring blood glucose using harmless, noninvasive far infrared light (FIL). Diabetes patients traditionally monitor their daily blood glucose levels with a conventional meter, which requires blood sampling from the fingertips.

In the past, scientists developed noninvasive methods for glucose measurement using near infrared light (NIL). This method works on the premise that NIL of certain wavelengths is selectively absorbed by glucose in the blood. Accurate and consistent measurement using this technique was difficult, however, because NIL is weakly absorbed by glucose as well as by water, protein, and hemoglobin. In contrast, FIL, with wavelengths of around 10 microns, is strongly absorbed by glucose, making it possible––theoretically––for patients to obtain more-sensitive and more-accurate measurements. However, the problem faced by researchers is that FIL penetrates only a few microns into the skin’s surface.

Researchers at Tohoku University’s Graduate School of Biomedical Engineering have developed a new technique to overcome this problem. The new method employs a small prism attached to the ends of flexible hollow-optical fibers to radiate FIL. With this technique, it is possible to irradiate the oral mucosa of the inner lips, which, unlike skin, do not have a thick horny layer, the researchers say.

In their experiments, blood glucose levels were measured in the oral mucosa with less than a 20% margin of error, which the investigators believe is good enough for clinical use.

Source: Tohoku University, February 4, 2016

Test Detects Early Parkinson’s Disease

Researchers at the Mayo Clinic in Arizona and at Banner Sun Health Research Institute have determined that testing a portion of a person’s submandibular gland may be a way to diagnose early Parkinson’s disease (PD). The study was published in Movement Disorders.

Currently, no accurate diagnostic tests are available for PD. The researchers believe that transcutaneous submandibular gland biopsy may provide the needed accuracy. The test involves inserting a needle into the submandibular gland and withdrawing the needle to obtain the core of gland tissue within. The researchers looked for an abnormal protein in the cells from patients with early PD and compared it with proteins from subjects without the disease.

The study involved 25 patients who had PD for less than five years and 10 control subjects without PD. Biopsies were taken from one submandibular salivary gland. The biopsies were done as an office procedure. The biopsied tissues were tested for evidence of the abnormal PD protein by study co-author Thomas Beach, MD, PhD, a neuropathologist at the Banner Sun Health Research Institute.

The abnormal PD protein was detected in 14 of the 19 patients who had enough tissue to study, providing positive results that need further investigation. The research team previously had shown that the biopsy could detect the protein in nine of 12 patients with advanced disease.

PD is a progressive disorder of the nervous system that affects movement as well as sleep, walking, balance, blood pressure, and smell. The disorder develops gradually, sometimes starting with a barely noticeable tremor in one hand. But while tremor may be the best-known sign of PD, the disorder also commonly causes stiffness or slowing of movement. Currently, a diagnosis is based on the patient’s medical history, on a review of signs and symptoms, on a neurological examination, and by ruling out other conditions. In a previous study, Drs. Adler and Beach found that up to 45% of PD patients may be misdiagnosed early in the disease. Although PD can’t be cured, medications may improve symptoms.

Source: Mayo Clinic, February 1, 2016

X-Ray and CT Scan Radiation Re-evaluated

The widespread belief that radiation from x-rays, computed tomography (CT) scans, and other medical imaging can cause cancer is based on an unproven, decades-old theoretical model, according to a study published in the American Journal of Clinical Oncology.

The model, known as linear no-threshold (LNT), is used to estimate cancer risks from low-dose radiation, such as medical imaging. But risk estimates based on this model “are only theoretical and, as yet, have never been conclusively demonstrated by empirical evidence,” corresponding author James Welsh, MD, of the Loyola University Medical Center, and his colleagues write. Moreover, the use of the LNT model drives unfounded fears and “excessive expenditures on putative but unneeded and wasteful safety measures.”

The LNT model dissuades many physicians from using appropriate imaging techniques and “discourages many in the public from getting proper and needed imaging, all in the name of avoiding any radiation exposure,” the article says.

The authors re-examined the original studies that led to adoption of the LNT model. This reappraisal found that the data reported in those studies do not actually support the LNT model.

The LNT model dates back to studies conducted in the 1940s, in which fruit flies were exposed to various doses of radiation. The scientists who performed those studies concluded that there is no safe level of radiation, thus giving rise to the LNT model that is used to this day. But their conclusion was unwarranted because their experiments had not been done at truly low doses, the new analysis contends. A study exposing fruit flies to low-dose radiation wasn’t conducted until 2009, and that study did not support the LNT model.

Any claim that low-dose radiation from medical imaging procedures is known to cause cancer “should be vigorously challenged, because it serves to alarm and perhaps harm, rather than educate,” Dr. Welsh and his colleagues write. The authors conclude that the LNT model “should finally and decisively be abandoned.”

Source: Loyola University Health System, February 3, 2016

Harvard Scientists Piggyback HIV Vaccine Onto Cold Viruses

In a new study published in the Annals of Internal Medicine, Harvard researchers say they successfully used cold viruses to deliver an experimental human immunodeficiency virus (HIV) vaccine to humans. Scientists have long sought to develop a vaccine against HIV, but the virus is especially stubborn.

In the study, the researchers piggybacked an experimental HIV vaccine onto two types of cold virus—adenovirus serotype 26 and adenovirus serotype 35. These viruses are rare, so most humans wouldn’t have developed immunity to them.

The researchers then injected 217 healthy people not infected with HIV in Boston and parts of Africa (Kenya, Rwanda, and South Africa) with at least one cold virus/HIV vaccine combo or placebo. Most of the subjects (78%) were black. Seven subjects dropped out and didn’t finish follow-up tests.

The findings showed that the cold viruses were a safe way to deliver the vaccine, and that the vaccine triggered an immune response in most of the study participants, according to co-author Dan Barouch, MD, PhD, a professor of medicine at Harvard Medical School.

One expert noted another positive finding that came from the study.

“They also found out that giving two vaccines over three months is just as good as waiting until six months for the second dose,” said Susan Buchbinder, MD director of an HIV research unit at the San Francisco Department of Public Health. “That is a big advantage, as more people are likely to complete their vaccination if the doses are closer together, and the immune response, if protective, will start protecting them sooner.”

Source: Medical Xpress, February 2, 2016

Sweat-Sensing Bracelet Could Be Next Wearable Technology

In a paper published in Nature, researchers describe a novel sweat monitor embedded on a translucent bracelet. The monitor consists of a sensor array and a flexible circuit board that measures the concentration of various chemicals in sweat, as well as a Bluetooth transmitter that beams the data to a phone. Study subjects wore it on their wrist or head, and scientists analyzed data during exercise sessions.

The researchers measured four chemicals—sodium, potassium, glucose, and lactate—with the proof-of-concept device, according to an article posted on the Stat website. The Nature article showed that the researchers could detect dehydration in runners based on the concentration of sodium in their sweat.

Lead author Ali Javey, PhD, of the University of California, Berkeley, said that sweat contains “a whole library” of chemicals––such as electrolytes, proteins, and heavy metals––that could present many opportunities for future studies. He said that his group is studying how a variety of diseases could be detected from sweat.

Sweat analysis is currently used to diagnose cystic fibrosis and to test for the use of illicit drugs. But the science of using sweat to more generally track a person’s health is far from fully developed, the authors concede.

In an accompanying editorial, Jason Heikenfeld, PhD, chief science officer of Eccrine Systems, which is working to develop similar wearables, described other potential applications. Sweat, he wrote, could help inform drug dosing by measuring how quickly patients metabolize drugs, or could reveal a person’s stress levels by monitoring their cortisol.

Sources: Nature, January 28, 2016; and Stat, January 27, 2016

DEVICE APPROVALS

Velano Needle-Free Blood Draw Device

Velano Vascular has received FDA clearance for a modified version of its needle-free blood draw device. The device is designed to reduce blood draw-related discomfort and anxiety for hospital inpatients, to provide a safer work environment for health care providers, and to standardize the current fragmented approaches to inpatient blood draws.

This second FDA clearance includes two modifications: the addition of a clamp for use with syringe draws (a frequent practice in pediatric patients) and a refinement to the product’s indication for use (IFU). The Velano device is attached to a peripheral intravenous (IV) catheter to draw blood directly into a vacuum tube or a syringe; the revised IFU removes a limitation in the earlier clearance that specified when the device could be used with in-dwelling peripheral IV catheters.

Source: Velano Vascular, Janaury 27, 2016

ChloraDerm Antimicrobial Dressing

Entrotech Life Sciences has received FDA 510(k) clearance for ChloraDerm, the first edge-to-edge transparent film dressing to provide a so-called “chlorhexidine advantage”—a colophony- and acid-free chlorhexidine matrix for wound- and catheter-site protection for up to seven days. Compared with non-antimicrobial dressings, ChloraDerm demonstrates substantially greater effectiveness against multidrug-resistant organisms at one, three, and seven days, without adding increased cost or complexity, according to the company.

ChloraDerm is used to cover and secure primary dressings and to protect wounds caused by percutaneous medical devices. The dressing achieves greater than 4 Log10 reduction against yeasts and gram-positive and gram-negative bacteria, including multiple drug-resistant organisms.

Source: Entrotech Life Sciences, January 25, 2016

Humulin R U-500 KwikPen For Glycemic Control

The FDA has approved Eli Lilly and Company’s Humulin R U-500 KwikPen (insulin human injection) 500 units/mL, a prefilled device containing Humulin R U-500, a concentrated formulation of insulin. Humulin R U-500 is the only FDA-approved insulin that is five times more concentrated than standard U-100 insulin, according to Lilly. This insulin is used to treat high blood sugar in people with type-1 and type-2 diabetes who need more than 200 units of insulin per day.

Previously, Humulin R U-500 was available only in a vial, administered with either a U-100 insulin syringe or a volumetric (tuberculin) syringe that required conversion to respective syringe “unit markings” or volume markings.

Source: Eli Lilly and Company, January 21, 2016

Altos Cervical Stabilization System

The FDA has cleared Altos (Centinel Spine, Inc.), a posterior cervical thoracic stabilization system indicated for implantation into either the lateral masses of the cervical spine or the pedicles of the cervical-thoracic spine. It is the first device approved for this indication.

The system includes both fully threaded and smooth-shank polyaxial screws with 80 degrees of freedom for insertion in the most demanding spinal anatomies. The system also provides laminar hooks, connectors, and straight and curved rods for customizable constructs.

Source: Centinel Spine, Inc., January 21, 2016

LifeWatch Mobile Cardiac Telemetry Patch

LifeWatch AG has received 510(k) clearance from the FDA for its LifeWatch Mobile Cardiac Telemetry Patch, a one-lead electrocardiogram system. The patch monitors the patient’s heartbeat for adverse cardiac events and transmits significant findings, in near-real time, to a clinical service center for immediate follow-up. The system is a lightweight alternative to traditional recording and transmitting devices, according to LifeWatch.

Source: LifeWatch AG, January 18, 2016

Modified TJF-Q180V Duodenoscope

The FDA has approved the Olympus TJF-Q180V duodenoscope with modifications to the device’s design and labeling intended to help reduce the risk of bacterial infections. Olympus voluntarily recalled its original model being used in health care facilities and made the needed repair.

Olympus modified its design of the elevator-channel sealing mechanism to create a tighter seal and to reduce the potential for leakage of patient fluids and tissue into the closed channel.

Source: FDA, January 15, 2016

BondEase Topical Surgical Skin Adhesive

OptMed Inc. has received 510(k) marketing clearance from the FDA for BondEase, a topical skin adhesive intended for the closure of surgical incisions and lacerations as an alternative to sutures and staples.

BondEase is a biocompatible topical skin adhesive that combines a new polymer technology with a delivery device. It is the only tissue adhesive for the topical approximation of skin that is not based on cyanoacrylate chemistry. The product is also the first topical surgical adhesive cleared via the FDA’s 510(k) process based on results from randomized controlled clinical trials.

Source: OptMed Inc., January 12, 2016

DEVICE SAFETY ISSUES

Inaccurate Blood Glucose Readings With Spotchem II

Arkray has recalled the Spotchem II Basic Panel-1 reagent test strip and the Spotchem II glucose reagent test strip because they may report falsely low blood glucose levels. Because the test strips are reporting low blood glucose when the true levels are above 265 mg/dL, there is a risk that health care providers would not diagnose hyperglycemia, including diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome, in a timely manner and would fail to treat elevated blood glucose levels.

Affected products include lot numbers PN5C26 and EA4M78; manufacturing dates of November 2014 to September 2015; and distribution dates of February 18, 2015 to October 13, 2015.

Source: FDA, January 28, 2016

Battery Problem With MOVES Ventilator System

Thornhill Research Inc. has recalled the MOVES ventilator system, a portable emergency transport ventilator, because excess glue on the battery connectors may prevent the battery from powering the device after the battery is stored. This issue may prevent the ventilator from providing patient breathing support and could cause patient injury or death.

Source: FDA, January 27, 2016

Brainlab Cranial Image-Guided Surgery System

Brainlab has recalled its Cranial Image-Guided Surgery (IGS) system because of potential inaccuracies in the display by the navigation system compared with the patient’s anatomy. This could lead to inaccurate, ineffective medical procedures and serious life-threatening injuries, including death.

The recall included the Brainlab Cranial IGS system and the Brainlab Cranial Navigation system (all existing versions before Cranial 3.0) with distribution dates of May 1996 to May 2015.

The Brainlab Cranial IGS system shows the area of interest and the position of an instrument relative to the patient’s anatomy to allow minimally invasive surgical procedures.

Source: FDA, January 15, 2016

OTHER DEVICE NEWS

INOpulse for PAH

Results of a phase 2 long-term extension study of Bellerophon Therapeutics’ INOpulse drug–device combination product for the treatment of pulmonary arterial hypertension (PAH) showed a sustained benefit among patients who received INOpulse 75 mcg/kg ideal body weight per hour (iNO 75) therapy for at least 12 hours a day combined with long-term oxygen therapy (LTOT). The active substance in INOpulse is pharmaceutical-grade nitric oxide. The portable device is designed for daily use by ambulatory patients.

In part one of the study, PAH patients showed a mean improvement in the six-minute walk distance (6MWD) of 52.4 meters after 16 weeks of therapy. In part two of the study, after 16 to 32 months of treatment, the patients who remained on iNO 75 for at least 12 hours a day combined with LTOT continued to maintain a mean increase in 6MWD of 55.2 meters.

Source: Bellerophon Therapeutics, February 9, 2016

Automated Cervical Cancer Test

The Confidence test portfolio (consisting of a human papillomavirus [HPV] test and an epigenetic biomarker) was evaluated in a European multicenter clinical trial with more than 7,000 cervical samples collected from more than 6,000 women. In HPV-positive women ages 25 years or older, sensitivity for severe cervical dysplasia or a worse condition at baseline was 91.9% and specificity was 74.4%.

Neumann Diagnostics Ltd. developed the molecular assay and plans to introduce it as a complement to current screening methods. When no signs of malignancy are found with conventional methods, the test can establish the individual risk of each woman for cervical pre-cancer or cancer, according to the company.

Source: Neumann Diagnostics Ltd., February 3, 2016