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Drug and Device News August 2017

NEW DRUG APPROVALS

Haegarda to Prevent Attacks In Hereditary Angioedema

The FDA has approved Haegarda (C1 esterase inhibitor subcutaneous [human], CSL Behring), the only subcutaneous therapy indicated for routine prophylaxis to prevent hereditary angioedema (HAE) attacks in adolescents and adults. HAE is a rare, genetic, and potentially life-threatening condition that causes painful, debilitating, and unpredictable episodes of swelling of the abdomen, larynx, face, and extremities, among other areas of the body.

The safety and efficacy of Haegarda were established in the phase 3 COMPACT (Clinical Studies for Optimal Management in Preventing Angioedema With Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy) trial, which showed that at the approved dose of 60 IU/kg, Haegarda reduced the median number of HAE attacks by 95% compared with placebo. In addition, the use of rescue medication was reduced by more than 99% versus placebo.

Haegarda is a self-administered, plasma-derived concentrate of C1 esterase inhibitor injected subcutaneously twice weekly.

Source: CSL Behring, June 23, 2017

Bevyxxa for VTE

Betrixaban (Bevyxxa, Portola Pharmaceuticals) has received FDA approval as the first anticoagulant for hospital and extended-duration prophylaxis (35 to 42 days) of venous thromboembolism (VTE) in adults hospitalized for an acute medical illness who are at risk for thrombo embolic complications due to moderate or severe restricted mobility and other risk factors for VTE.

In a phase 3 study, betrixaban reduced the incidence of deep-vein thrombosis and pulmonary embolism compared with enoxaparin plus placebo (4.4% versus 6.0%, respectively; relative risk, 0.75), with no significant increase in major bleeding (0.67% versus 0.57%).

Betrixaban is expected be launched between August and November 2017.

Source: Portola Pharmaceuticals, June 23, 2017

Mydayis for ADHD

The FDA has approved Mydayis (mixed salts of a single-entity amphetamine product, Shire), a once-daily treatment consisting of three types of drug-releasing beads for patients 13 years of age and older with attention-deficit/hyperactivity disorder (ADHD). Mydayis is not intended for use in children 12 years of age and younger. Shire expects to launch the product in the United States in the third quarter of 2017.

The FDA’s approval of Mydayis was based on results from 16 clinical studies that evaluated the treatment in more than 1,600 patients, including adolescents (13 to 17 years of age) and adults with ADHD. Improvement on the Permanent Product Measure of Performance, an objective, skill-adjusted math test that measures attention in ADHD patients, reached statistical significance beginning at two or four hours post-dose and lasting up to 16 hours post-dose.

Source: Shire, June 20, 2017

Baxdela for Skin Infections

The FDA has given the green light to delafloxacin (Baxdela, Melinta Therapeutics) for the treatment of adults with acute bacterial skin and skin-structure infections (ABSSSI) caused by susceptible bacteria. Delafloxacin is a fluoroquinolone with activity against both gram-positive and gram-negative pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). It is available in both intravenous (IV) and oral formulations.

The FDA’s approval was based on data from two phase 3 trials in patients with ABSSSI. These studies demonstrated that monotherapy with IV or oral delafloxacin was statistically noninferior to vancomycin plus aztreonam at the FDA-designated primary endpoint of an early clinical response at 48 to 72 hours.

Source: Melinta Therapeutics, June 19, 2017

Rebinyn for Hemophilia B

The FDA has approved the biologics license application for Rebinyn (coagulation factor IX [recombinant], glyco PEGylated, Novo Nordisk) for on-demand treatment and control of bleeding episodes and the perioperative management of bleeding around the time of surgery in adults and children with hemophilia B. Rebinyn is an extended half-life factor IX molecule. Novo Nordisk expects to launch the product in the United States in the first half of 2018.

Source: Novo Nordisk, June 1, 2017

Generic Approvals and Launches

Emtricitabine/Tenofovir Disoproxil Fumarate Tablets

The FDA has approved an application by Teva Pharmaceuticals USA to market emtricitabine and tenofovir disoproxil fumarate tablets, 200 mg/300 mg. This is the first generic version of Truvada (Gilead Sciences), which is indicated for the treatment of human immunodeficiency virus 1 (HIV-1) in combination with other antiretroviral agents, and for pre-exposure prophylaxis (PrEP) in combination with safer sex practices to prevent sexually acquired HIV infection in adults at high risk.

Source: FDA, June 8, 2017

Mesalamine Delayed-Release Tablets

The marketing of mesalamine delayed-release tablets USP, 1.2 g, by Zydus Pharmaceuticals (USA), Inc., has secured FDA approval. The medication, the first generic version of Lialda (Shire) delayed-release tablets, is indicated for the induction of remission in adults with active, mild-to-moderate ulcerative colitis and for the maintenance of remission of ulcerative colitis.

Source: FDA, June 5, 2017

Atomoxetine Capsules

Glenmark Pharmaceuticals Ltd., Aurobindo Pharma Ltd., Teva Pharmaceuticals USA, and Apotex, Inc., have received FDA approval to market atomoxetine capsules in 10-mg, 18-mg, 25-mg, 40-mg, 60-mg, 80-mg, and 100-mg strengths. These are the first generic versions of Strattera (Lilly), used for the treatment of attention-deficit/hyperactivity disorder.

Source: FDA, May 30, 2017

Entecavir Tablets

Zydus Cadila has received FDA approval to market 0.5-mg and 1.0-mg tablets of entecavir, a nucleoside and nucleotide analogue indicated for the treatment of patients with hepatitis B virus infection.

Source: Zydus Cadila, June 27, 2017

Immediate-Release Doxycycline Hyclate

The FDA has approved marketing of doxycycline hyclate immediate-release tablets, 75 mg and 150 mg, by Mayne Pharma Group, which launched the product immediately in the U.S. This is a generic version of Acticlate (Aqua Pharmaceuticals), a tetracycline-class antibacterial indicated for the treatment of several infections, including adjunctive therapy in severe acne.

Source: Mayne Pharma Group, June 15, 2017

Amantadine Capsules

Strides Shasun has received FDA approval for amantadine hydrochloride capsules USP, 100 mg, which are used to treat Parkinson’s disease and to treat pain in herpes zoster.

Source: Strides Shasun, June 8, 2017

Azacitidine for Injection

The FDA has approved the sale of azacitidine for injection by Breckenridge Pharmaceutical/Natco Pharma in a 100-mg, single-dose vial—a generic version of Vidaza (Celgene Corporation), a chemotherapy drug indicated to treat patients with myelodysplastic syndrome.

Source: Breckenridge Pharmaceutical, June 26, 2017

Extended-Release Niacin

The FDA has approved the sale of niacin extended-release tablets USP, 500 mg and 1,000 mg, by Kremers Urban Pharmaceuticals/Lannett Company—the therapeutic equivalent of Niaspan (AbbVie).

Source: Lannett Company, June 19, 2017

Acyclovir for Injection

Zydus Cadila Healthcare has received FDA approval to market the antiviral medication acyclovir for injection USP in strengths of 500 mg per vial and 1,000 mg per vial.

Source: Zydus Cadila Healthcare, June 15, 2017

Sevelamer Carbonate Oral Suspension

Aurobindo Pharma has received FDA approval to market sevelamer carbonate oral suspension, 0.8 g and 2.4 g—the therapeutically equivalent generic version of Renvela oral suspension (Genzyme). The product was launched immediately.

Source: Aurobindo Pharma, June 15, 2017

NEW INDICATIONS

Darzalex for Multiple Myeloma

The FDA has approved the immunotherapy daratumumab (Darzalex, Janssen) in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide (an immunomodulatory agent) and a proteasome inhibitor (PI). Clinical trial results showed an overall response rate of 59% with daratumumab in combination with pomalidomide and dexamethasone in these patients.

Daratumumab, the first CD38-directed antibody, was first approved by the FDA in November 2015 as monotherapy for patients with multiple myeloma who have received at least three lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. It received additional approvals in November 2016 in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Source: Janssen, June 16, 2017

Dysport for Lower-Limb Spasticity

The FDA has expanded the approved uses of Dysport (abobotulinumtoxinA, Ipsen Biopharmaceuticals) by adding the treatment of lower-limb spasticity in adults. Dysport is an injectable form of botulinum toxin type A (BoNT-A), which is isolated and purified from Clostridium bacteria producing BoNT-A.

In July 2015, Dysport was approved for the treatment of upper-limb spasticity in adults. One year later, it was cleared for the treatment of pediatric patients 2 years of age and older with lower-limb spasticity, making it the only botulinum toxin that the FDA has approved for this indication.

Source: Ipsen Biopharmaceuticals, June 16, 2017

NEW FORMULATION

Rituxan Hycela SC Injection For Multiple Blood Cancers

The FDA has approved Rituxan Hycela (Genentech/Halozyme)—rituximab coformulated with Halozyme’s human hyaluronidase Enhanze technology—for subcutaneous injection in multiple blood cancer indications, including follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. In March, the FDA’s Oncologic Drug Advisory Committee voted unanimously (11 to 0) in favor of the risk–benefit profile of rituximab/human hyaluronidase subcutaneous injection.

Source: Genentech, June 22, 2017

FDA REVIEW ACTIVITIES

Priority Review Designation

Vyxeos for AML

The FDA has accepted for filing with priority review the new drug application for Vyxeos (cytarabine and daunorubicin liposome injection, Jazz Pharmaceuticals), an investigational treatment for patients with acute myeloid leukemia. Vyxeos consists of cytarabine and daunorubicin encapsulated within a nanoscale liposome at a 5:1 molar ratio.

Source: Jazz Pharmaceuticals, May 31, 2017

Fast-Track Designations

Nelotanserin for Visual Hallucinations in Dementia

The FDA has granted fast-track status to nelotanserin (Axovant Sciences), a serotonin 2A receptor inverse agonist, for the treatment of visual hallucinations in patients with dementia with Lewy bodies, which affects one million people in the United States. There are no approved treatments for the disease.

Source: Axovant Sciences, June 19, 2017

SYNB1020 for Hyperammonemia

Synlogic has received a fast-track designation from the FDA for SYNB1020—an oral, investigational medication for the treatment of patients with hyperammonemia in a group of rare genetic diseases called urea cycle disorders. SYNB1020, the first in a new class of living, “synthetic biotic” medications under development by Synlogic, is being evaluated in a phase 1 study in healthy volunteers to assess its safety and tolerability. SYNB1020 is also under development as a potential treatment for patients with hyperammonemia associated with hepatic encephalopathy due to cirrhosis.

Source: Synlogic, June 26, 2017

Breakthrough Therapy Status

CR845 for Pruritus in Hemodialysis

The FDA has granted a breakthrough therapy designation to intravenous CR845 (Cara Therapeutics) for the treatment of moderate-to-severe uremic pruritus in patients with chronic kidney disease undergoing hemodialysis. CR845 is a peripherally acting kappa-opioid receptor agonist in development for the treatment of acute and chronic pain and pruritus.

Source: Cara Therapeutics, June 23, 2017

Orphan Drug Designations

IDN-7314 for Sclerosing Cholangitis

The FDA has granted an orphan drug designation to the drug candidate IDN-7314 (Conatus Pharmaceuticals) for the treatment of patients with primary sclerosing cholangitis, a disease that affects bile ducts in the liver, which in turn can lead to cirrhosis and liver failure. IDN-7314 is an orally active pan-caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and apoptosis.

Source: Conatus Pharmaceuticals, June 26, 2017

Impavido for Amebic Encephalitis

Profounda, Inc., has received the FDA’s orphan drug designation for miltefosine (Impavido) as a treatment for patients with granulomatous amebic encephalitis (GAE), a serious infection of the brain and spinal cord.

One of the causes of GAE is the Balamuthia amoeba, which is thought to enter the body when soil or dust containing Balamuthia comes in contact with skin wounds and cuts, is inhaled, or enters the mouth. Balamuthia amoebas then travel to the brain through the blood stream and cause GAE.

Miltefosine is the only oral treatment approved by the FDA for visceral, mucosal, and cutaneous leishmaniasis (a rare tropical parasitic disease).

Source: Profounda, June 28, 2017

PRP for Pancreatic Cancer

Propanc Biopharma has received an FDA orphan drug designation for PRP—a solution for once-daily intravenous administration of a combination of two pancreatic proenzymes, trypsinogen and chymo-trypsinogen, for the treatment of patients with pancreatic cancer. PRP reprograms cancer cells to become benign and essentially forces them to behave as normal cells, according to the company.

Source: Propanc Biopharma, June 26, 2017

IT-139 for Pancreatic Cancer

The FDA has granted orphan drug status to IT-139 (Intezyne Technologies), a GRP78 inhibitor, for the treatment of patients with pancreatic cancer. IT-139 downregulates the stress induction of GRP78 in cancer cells. GRP78 is a critical cell-survival protein that is associated with drug resistance and tumor proliferation.

Source: Intezyne Technologies, June 20, 2017

Oratrope for Growth Hormone Deficiency

The FDA has granted an orphan drug designation to ibutamoren mesylate (Oratrope, Ammonette Pharma) for the treatment of patients with growth hormone (GH) deficiency.

Ibutamoren mesylate mimics the effects of ghrelin, a natural hormone found in the stomach that controls the release of GH from the pituitary gland. Ibutamoren is expected to be administered orally as a daily minipill, allowing the body to produce its own GH in a physiologically pulsatile manner over 24 hours, unlike the single daily bolus of exogenous GH delivered at present by daily injection.

Source: Ammonette Pharma, June 19, 2017

LipidRescue for Anesthetic Systemic Toxicity

The FDA has granted an orphan drug designation to LipidRescue therapy (ResQ Pharma) for patients with local anesthetic systemic toxicity. The treatment involves administering a lipid emulsion to reduce the life-threatening clinical manifestations of toxicity from excessive doses of certain lipophilic drugs.

Source: ResQ Pharma, June 18, 2017

Tavokinogene Telsaplasmid For Melanoma

The FDA has granted orphan drug status to tavokinogene telsaplasmid (pIL-12, OncoSec Medical, Inc.) for the treatment of patients with unresectable metastatic melanoma. Tavokinogene telsaplasmid is the active biologic agent in OncoSec’s ImmunoPulse IL-12.

The phase 2 Anti–PD-1 IL-12 Stage III/IV Combination Electroporation Study (PISCES) will evaluate ImmunoPulse IL-12 in combination with pembrolizumab (Keytruda, Merck) in patients with a histologic diagnosis of melanoma with progressive, locally advanced, or metastatic disease (stage III or IV) whose illness is progressing or has progressed during an approved anti-programmed death-1 therapy. The study’s primary endpoint is the best overall response rate.

Source: OncoSec Medical, June 8, 2017

New or Revised Applications

Xgeva for Multiple Myeloma

The FDA has accepted a supplemental biologics license application for denosumab (Xgeva, Amgen) that seeks to expand the approved indication for the prevention of fractures and other skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma. The FDA has set a Prescription Drug User Fee Act action date of February 3, 2018.

Denosumab is the first fully human monoclonal antibody that binds to and neutralizes RANK ligand—a protein essential for the formation, function, and survival of osteoclasts, which break down bone—thereby inhibiting osteoclast-mediated bone destruction.

Source: Amgen, June 19, 2017

Repatha Cardiovascular Outcomes

Amgen has submitted a supplemental biologics license application to the FDA for evolocumab (Repatha), a pro-protein convertase subtilisin/kexin type 9 inhibitor. The submission was based on results from the evolocumab cardiovascular outcomes study (FOURIER), in which maximally reducing low-density lipoprotein-cholesterol (LDL-C) levels with evolocumab, beyond what is possible with the current best therapy alone, led to a further reduction in major cardiovascular events, including heart attacks, strokes, and coronary revascularizations.

Consistent with recent trials of more-intensive LDL lowering, there was no observed effect on cardiovascular mortality. Similarly, no effect was observed on hospitalization for unstable angina.

Source: Amgen, June 5, 2017

Jatenzo for Testosterone Replacement

Clarus Therapeutics has resubmitted a new drug application for Jatenzo (oral testosterone undecanoate)—formerly known as Rextoro—for the treatment of low testosterone in hypogonadal men. The new submission addressed all the points raised by the FDA in a complete response letter issued to Clarus.

In the phase 3 inTUne trial, 87% of men treated with Jatenzo achieved average circulating levels of testosterone in the normal range, based on the primary efficacy analysis mandated by the FDA. All sensitivity analyses yielded similar efficacy (range, 86% to 90%).

Source: Clarus Therapeutics, June 26, 2017

Dexycu for Use After Cataract Surgery

The FDA has accepted for filing Icon Bioscience’s new drug application for Dexycu (IBI-10090). The FDA has established an action date under the Prescription Drug User Fee Act of February 12, 2018.

Dexycu employs Verisome drug-delivery technology to dispense a sustained-release, biodegradable formulation of the anti-inflammatory agent dexamethasone directly into the anterior chamber of the eye through a single injection administered by the physician immediately after cataract surgery.

Source: Icon Bioscience, June 26, 2017

Tavalisse for Chronic ITP

The FDA has accepted for filing a new drug application for the use of fostamatinib disodium (Tavalisse, Rigel Pharmaceuticals) in patients with chronic or persistent immune thrombocytopenia (ITP). The Prescription Drug User Fee Act action date is April 17, 2018. The FDA previously granted orphan drug status to fostamatinib for the treatment of patients with ITP. Fostamatinib is an oral investigational drug designed to inhibit SYK kinase, a key signaling member in the immune process that leads to platelet destruction in ITP.

Source: Rigel Pharmaceuticals, June 19, 2017

BIC/FTC/TAF for HIV-1 Infection

Gilead Sciences has submitted a new drug application to the FDA for an investigational, once-daily, single-tablet regimen containing bictegravir (50 mg) (BIC), a novel investigational integrase strand transfer inhibitor, and emtricitabine/tenofovir alafenamide (200 mg/25 mg) (FTC/TAF) for the treatment of human immunodeficiency virus 1 (HIV-1) infection in adults. In phase 3 clinical trials, BIC/FTC/TAF demonstrated high rates of virological suppression and no treatment-emergent resistance through 48 weeks of therapy among treatment-naïve adults and among virologically suppressed adults who switched regimens.

Source: Gilead Sciences, June 12, 2017

BIVV001 for Hemophilia A

The FDA has accepted an investigational new drug application for BIVV001 (rFVIIIFc-VWF-XTEN, Bioverativ), a factor VIII therapy designed to potentially extend protection from bleeds with prophylaxis dosing of once weekly or longer in patients with hemophilia A.

BIVV001 builds on Bioverativ’s existing Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to potentially extend its time in circulation. It is the only investigational factor VIII therapy in development that is designed to overcome the von Willebrand factor ceiling, which is believed to impose a half-life limitation on current factor VIII therapies.

Source: Bioverativ, June 12, 2017

Dolutegravir/Rilpivirine for HIV-1

ViiV Healthcare has made a regulatory submission to the FDA for a single-tablet, two-drug regimen of dolutegravir (Tivicay, ViiV Healthcare) and rilpivirine (Edurant, Janssen Sciences Ireland). If approved, it will be the first two-drug regimen for the maintenance treatment of patients with human immunodeficiency virus 1 (HIV-1) infection and will offer virally suppressed patients the option to switch to a regimen that does not include a nucleotide reverse transcriptase inhibitor (NRTI).

Dolutegravir is an HIV-1 integrase strand transfer inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adult and pediatric patients weighing at least 30 kg. Rilpivirine is a non-NRTI.

In June 2014, ViiV Healthcare and Janssen Sciences Ireland announced a partnership to investigate the potential of combining dolutegravir and rilpivirine in a single tablet to expand the treatment options available to patients with HIV infection.

Source: Janssen, June 1, 2017

Complete Response Letters

Trintellix Label Update

The FDA has issued a complete response letter (CRL) on a supplemental new drug application requesting that new data on treating aspects of cognitive dys-function in adults with major depressive disorder be included in the clinical trials section of the prescribing information for vortioxetine (Trintellix, Lundbeck/Takeda). The FDA approved vortioxetine in September 2013 for the treatment of adults with major depressive disorder. The CRL does not change the FDA-approved prescribing information for vortioxetine.

The mechanism of the antidepressant effect of vortioxetine is not fully understood. It is an inhibitor of serotonin (5-HT) reuptake, and that is thought to be a mechanism of its action. It is also an agonist at 5-HT1A receptors, a partial agonist at 5-HT1B receptors, and an antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors. The contribution of each of these activities to the antidepressant effect of vortioxetine has not been established.

Source: Lundbeck, June 23, 2017

Neulasta Biosimilar

The FDA has issued a complete response letter (CRL) on the biologics license application for CHS-1701, a biosimilar candidate for pegfilgrastim (Neulasta, Amgen) developed by Coherus Bio-Sciences. The CRL primarily focused on the agency’s request for a reanalysis of a subset of subject samples with a revised immunogenicity assay, and on requests for additional manufacturing-related process information.

Amgen’s pegfilgrastim is a covalent conjugate of recombinant methionyl human granulocyte colony-stimulating factor (G-CSF, filgrastim) and monomethoxypolyethylene glycol. Filgrastim is obtained from the bacterial fermentation of a strain of Escherichia coli transformed with a genetically engineered plasmid containing the human G-CSF gene.

Source: Coherus BioSciences, June 12, 2017

DRUG SAFETY ISSUES

Hospira Injectables Recall May Affect Drug Shortages

A Hospira recall of injectable products may affect critical drug shortages, the FDA says, and three other companies that repackaged or compounded those medications have also issued recalls.

Citing a potential lack of sterility assurance, Hospira (a Pfizer subsidiary) recalled 42 lots of sodium bicarbonate injection 8.4%, 50-mL vials; five lots of Neut (sodium bicarbonate 4% additive solution), 5-mL vials; seven lots of potassium phosphate injection, 45-mM vials; and five lots of Quelicin (succinylcholine chloride injection), 200-mg/10-mL vials. All but Quelicin are in shortage.

Microbial growth was detected during a routine simulation of the manufacturing process. The recall notice cited a “reasonable probability” that patients using impacted products could have adverse effects ranging from fever, chills, and malaise to systemic invasive mycoses or systemic bacterial sepsis. Microorganisms have not been found in any distributed products, and no adverse events have been reported by the companies that issued recalls.

Based on Hospira’s recall, PharMEDium Services recalled 76 lots of compounded potassium phosphate and succinylcholine chloride. Advanced Pharma (doing business as Avella of Houston) recalled 17 lots of repackaged or compounded potassium phosphate and succinylcholine products. Fagron Sterile Services recalled three lots of succinylcholine chloride. Virtually all the products in these three recalls were in bags or syringes.

“FDA is concerned about how this recall will affect ongoing critical shortages and is working closely with Pfizer to resolve them by addressing the underlying causes,” the agency says. Based on stability data provided by Pfizer, the use dates of some other syringe products have been extended.

Due to similar concerns about a lack of sterility assurance, an additional company, Alvogen, recalled seven lots of clindamycin injection ADD-Vantage vials that were manufactured for Alvogen by Hospira. This drug is not in shortage.

Sources: FDA, June 16 and 23, 2017; Hospira, June 15, 2017; Alvogen, June 16, 2017; Advanced Pharma, June 22, 2017; Fagron, June 23, 2017; and PharMEDium, June 27, 2017

Avella Nitroglycerin

Advanced Pharma (Avella) is recalling 31 lots of unexpired nitroglycerin injection in 5% dextrose produced at its Houston, Texas, location between March 3 and May 31, 2017, because of subpotency shown in laboratory tests. An extreme and unexpected reduction in dose could lead to a delay in treatment, disruption of clinical care of the patient, and worsening of the patient’s condition.

Source: FDA and Advanced Pharma, June 15, 2017

Phillips Topical Products

Phillips Company recalled all lots of Tetrastem, Diabecline, Tetracycline-ABC, VenomX, Acneen, StaphWash, StringMed, NoPain, and LidoMed after an FDA inspection found manufacturing practices that call into question the safety, identity, strength, quality, and purity of unexpired drug products made during the past three years. The topical antibiotic products are intended for treatment of minor cuts, scrapes, and burns, or as skin cleansers or hair-growth promoters. All products are distributed in 5-mL dropper bottles for topical application.

Source: FDA, June 14, 2017

CLINICAL TRIAL NEWS

Adcetris for Hodgkin’s Lymphoma

The phase 3, randomized, multicenter ECHELON-1 trial met its primary endpoint of a statistically significant improvement in modified progression-free survival (mPFS) with brentuximab vedotin (Adcetris, Takeda Pharmaceutical Company) compared with the control arm as part of a first-line combination chemotherapy regimen in 1,334 patients with previously untreated, advanced classical Hodgkin’s lymphoma (HL). Brentuximab vedotin is an antibody–drug conjugate directed to CD30, a defining marker of classical HL.

Patients in the ECHELON-1 study were randomly assigned to receive either a combination of brentuximab vedotin plus AVD (adriamycin, vinblastine, and dacarbazine) or ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), a standard of care for patients with first-line HL. The trial results demonstrated that combination treatment with brentuximab vedotin resulted in a statistically significant improvement in mPFS compared with the control arm (hazard ratio, 0.77; P = 0.035). The two-year modified mPFS rate for patients in the brentuximab vedotin arm was 82.1% compared with 77.2% in the control arm.

Source: Takeda, June 26, 2017

Eptinezumab for Migraine

Eptinezumab (Alder BioPharmaceuticals), an investigational monoclonal antibody for migraine prevention, met the primary and key secondary endpoints in a pivotal phase 3 study involving patients with frequent episodic migraine.

The primary endpoint––the average duration of statistically significant reductions in monthly migraine days from baseline during weeks 1 through 12—was 4.3 monthly migraine days for 300 mg (P = 0.0001) and 3.9 days for 100 mg (P = 0.0179) compared with 3.2 days for placebo. The rates of a 75% reduction in monthly migraine days achieved from weeks 1 through 12—a key secondary endpoint—were 29.7% for 300 mg (P = 0.0007) and 22.2% for 100 mg (not statistically significant) compared with 16.2% for placebo.

Source: Alder BioPharmaceuticals, June 27, 2017

Rubraca for Ovarian Cancer

The confirmatory phase 3 ARIEL3 trial of rucaparib (Rubraca, Clovis Oncology) has achieved its primary endpoint of improved progression-free survival (PFS), as determined by investigator review, in each of the three populations studied. PFS also improved in the rucaparib group compared with the placebo group by blinded independent central review, a key secondary endpoint. Based on these findings, Clovis plans to submit a supplemental new drug application to the FDA by October 2017 for a second-line and later maintenance treatment indication for women with platinum-sensitive ovarian cancer who have responded to their most recent platinum therapy.

In December 2016, rucaparib was the first poly ADP-ribose polymerase inhibitor approved by the FDA as monotherapy for patients with BRCA mutation-associated (germline and/or somatic) advanced ovarian cancer who have been treated with two or more chemotherapies.

Source: Clovis Oncology, June 19, 2017

Simponi Aria for Psoriatic Arthritis

Results from the pivotal phase 3 GO-VIBRANT trial demonstrated the efficacy of the intravenously administered anti-tumor necrosis factor-alpha therapy golimumab (Simponi Aria, Janssen) in the treatment of active psoriatic arthritis. In the study, 75.1% of patients treated with golimumab 2 mg/kg achieved at least a 20% improvement in arthritis signs and symptoms, as measured by American College of Rheumatology criteria (ACR20), at week 14 (the study’s primary endpoint) compared with 21.8% of patients given placebo (P < 0.001). Golimumab also achieved significant improvements across all secondary endpoints, which evaluated improvements in skin symptoms, joint damage, and health-related quality-of-life measures.

Source: Janssen, June 14, 2017

Alecensa for Lung Cancer

In a phase 3 study, alectinib (Alecensa, Roche) significantly reduced the risk of disease worsening or death (progression-free survival [PFS]) by more than half (53%) compared with crizotinib (Xalkori, Pfizer) when administered as a first-line treatment in patients with anaplastic lymphoma kinase-positive advanced non–small-cell lung cancer (hazard ratio [HR], 0.47; P < 0.0001). Investigator-reported median PFS, the study’s primary endpoint, was not reached in patients treated with alectinib compared with 11.1 months in those who received crizotinib.

The randomized ALEX trial, which included 303 patients in 31 countries, also demonstrated that alectinib reduced the risk of disease progression in the central nervous system (CNS) by 84% compared with crizotinib (HR, 0.16; P < 0.0001). The 12-month cumulative rates of CNS progression for subjects with or without existing CNS metastases at baseline were 9.4% for those treated with alectinib and 41.4% for those receiving crizotinib.

Source: Roche, June 5, 2017

Sirukumab for RA

Long-term results from SIRROUND-T, a pivotal phase 3 trial, have shown that sirukumab (Janssen/Cilag International) improved the signs and symptoms of moderately to severely active rheumatoid arthritis (RA) through 52 weeks of treatment in adults with an inadequate response to and/or intolerance of anti-tumor necrosis factor-alpha treatments. More than half of the patients receiving either sirukumab 50 mg or 100 mg achieved at least a 20% improvement in the signs and symptoms of disease (the American College of Rheumatology’s ACR20 criteria) at week 52 (54.3% for sirukumab 50 mg; 59.3% for sirukumab 100 mg).

Sirukumab is a fully human mono clonal immunoglobulin G1 kappa antibody that selectively blocks circulating interleukin 6, a naturally occurring protein that is believed to play a role in autoimmune conditions such as RA.

Source: Janssen, June 14, 2017

Bronchitol for Cystic Fibrosis

An international phase 3 trial of Bronchitol (mannitol, Pharmaxis Ltd.) in adults with cystic fibrosis met its primary endpoint. The study was designed to gain U.S. marketing approval, and an FDA submission is expected in 2018. Bronchitol is a spray-dried form of mannitol, delivered to the lungs by a portable inhaler.

The randomized, double-blind, parallel-group study demonstrated the superiority of Bronchitol versus the comparator on the change from baseline in forced expiratory volume in one second during the 26-week treatment period (the study’s primary endpoint), with an effect of 54 mL (P = 0.020), corresponding to a 2.2% relative change (P = 0.025).

Source: Pharmaxis, June 13, 2017

Ertugliflozin for Diabetes

Two phase 3 studies of ertugliflozin (Merck) have met their primary endpoints. Ertugliflozin is an investigational oral sodium glucose cotransporter 2 inhibitor in development to help improve glycemic control in adults with type-2 diabetes. In the two studies, both dosages of ertugliflozin (5 mg daily and 15 mg daily) achieved statistically significant reductions in hemoglobin A1C when added to metformin or in initial coadministration with sitagliptin (Januvia, Merck).

Marketing applications for ertugliflozin and for two fixed-dose combination products (ertugliflozin plus sitagliptin, and ertugliflozin plus metformin) are under review at the FDA. The Prescription Drug User Fee Act action date is December 2017 for the three drugs.

Source: Merck, June 10, 2017

Upadacitinib for RA

Positive results have been reported from the phase 3 SELECT-NEXT trial, which evaluated upadacitinib (AbbVie), an investigational, oral Janus kinase 1–selective inhibitor, in patients with moderate-to-severe rheumatoid arthritis who did not adequately respond to treatment with conventional synthetic disease-modifying antirheumatic drugs.

The results showed that, after 12 weeks of treatment, both doses of upadacitinib (15 mg and 30 mg) met the study’s primary endpoints of a 50% improvement in tender or swollen joint counts and a 50% percent improvement in three of five other criteria (the American College of Rheumatology’s ACR50 standard), along with low disease activity. Of the patients treated with a 15-mg or 30-mg oral, once-daily dose of upadacitinib, 38% and 43% achieved ACR50, respectively, compared with 15% of patients given placebo.

Source: AbbVie, June 7, 2017

DEVICE APPROVALS

Symjepi Auto-Injector For Allergic Reactions

The FDA has approved Symjepi (epinephrine injection, USP, 1:1,000 [0.3 mg], Adamis Pharmaceuticals) for the emergency treatment of allergic reactions (type I), including anaphylaxis. Symjepi provides two prefilled, single-dose syringes of epinephrine (adrenaline), considered the drug of choice for immediate administration in acute anaphylactic reactions to insect stings or bites; in allergic reaction to foods (such as nuts), drugs, and other allergens; and in idiopathic or exercise-induced anaphylaxis.

Adamis Pharmaceuticals said it intends Symjepi to be a lower-cost rival to Mylan’s EpiPen. The company is looking for a marketing partner and plans to set a price for the product before its launch in the second half of this year.

Source: Adamis Pharmaceuticals, June 15, 2017

Portable Emergency Life-Support System

Thornhill Medical’s MOVES SLC portable emergency life-support system has received 510(k) clearance from the FDA. This approval expands the capabilities of the current system, which now include pediatric settings, expanded patient-monitoring modes, new ventilator modes, and a remote monitoring and control interface.

MOVES SLC is the world’s only portable emergency life-support system with a built-in oxygen concentrator. It extracts oxygen from the air to deliver 85% FiO2 concentrations for ventilated patients, without oxygen tanks. This helps make the MOVES SLC system 50% smaller and 60% lighter than standard portable life-support systems.

Source: Thornhill Medical, June 8, 2017

VNS Therapy for Drug-Resistant Epilepsy in Children From Age 4

The FDA has approved the use of the VNS Therapy system (LivaNova PLC) in patients as young as 4 years of age with partial onset seizures that are refractory to antiepileptic medications.

VNS Therapy is the only FDA approved device for drug-resistant epilepsy in this pediatric population. Previously, VNS Therapy was FDA-approved for patients ages 12 and older. Studies show that earlier use of VNS Therapy offers better long-term outcomes for children.

VNS Therapy is delivered through an implanted device that sends mild pulses to the vagus nerve at regular intervals throughout the day in an effort to stop seizures before they start. An additional dose of therapy may stop or shorten a seizure, decrease its intensity, and shorten recovery time. VNS Therapy includes a short outpatient procedure that takes about an hour. Most people go home the same day.

Sources: LivaNova PLC, June 29, 2017; LivaNova.com

HIV Antigen–Antibody Assay

The FDA has approved the Elecsys HIV combi PT assay (Roche)—a fourth-generation human immunodeficiency virus (HIV) combination antigen–antibody test. The immunoassay is designed for the in vitro qualitative determination of HIV-1 p24 antigen and antibodies to HIV-1 (HIV-1 groups M and O) and HIV-2 in human serum and plasma. Intended for use as an aid in the diagnosis of HIV-1 and/or HIV-2 infection, including acute and primary HIV-1 infection, the test is able to detect both the antigen and antibodies simultaneously.

Source: Roche, June 23, 2017

Blood Test for Latent TB

The FDA has approved QuantiFERON-TB Gold Plus (Qiagen), the fourth generation of the market-leading blood test for detecting latent tuberculosis infection. Qiagen submitted the test in a premarket-approval supplement in late 2016. U.S. commercialization of the test is planned later this year.

Source: Qiagen, June 8, 2017

DEVICE SAFETY ISSUES

MedWatch Safety Alerts

The FDA has posted MedWatch Safety Alerts for the following devices:

Venture catheters by Vascular Solutions: All unexpired RX, OTW, and CS versions recalled because excess material may split or separate during use. Material in the patient’s bloodstream can result in serious adverse health consequences, such as the development of blood clots. Updated on June 23, 2017.

System CS100, CS100i, and CS300 intra-aortic balloon pumps by Datascope: Field correction—potential electrical failure test code. Report of failure of the device to initiate therapy. A complaint involving a CS300 was associated with a patient death. An electrical test failure code #58 is caused by a solenoid valve requiring more power than the solenoid driver board can deliver to open the valve. Posted on June 19, 2017.

LeadCare testing systems (with blood obtained from a vein) by Magellan Diagnostics: The class I recall was expanded because of the risk of inaccurate results. Falsely lower test results may lead to improper patient management and treatment for lead exposure or poisoning. Updated on June 6, 2017.