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Drug and Device News January 2017

NEW DRUG APPROVALS

Xultophy for Type-2 Diabetes

The FDA has approved Xultophy 100/3.6 (insulin degludec 100 units/mL and liraglutide 3.6 mg/mL injection, Novo Nordisk). The product, a once-daily combination of Tresiba (insulin degludec injection) and Victoza (liraglutide injection), is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes that is in adequately controlled on less than 50 units of basal insulin daily or on less than or equal to 1.8 mg of liraglutide daily. Xultophy 100/3.6 belongs to a new class of diabetes treatments that combine a basal insulin and a glucagon-like peptide-1 receptor agonist in a single, once-daily injection.

The approval of Xultophy 100/3.6 was based on efficacy and safety data from the DUAL clinical development program. In three DUAL trials involving a total of 1,393 adults with type-2 diabetes, patients who were inadequately controlled on liraglutide or basal insulin therapy and switched to Xultophy 100/3.6 achieved reductions in hemoglobin A1c (HbA1c). For adults uncontrolled on basal insulin, Xultophy 100/3.6 demonstrated significant reductions in HbA1c from baseline of 1.67% and 1.94%.

Source: Novo Nordisk, November 21, 2016

Intrarosa for Pain During Sex For Postmenopausal Women

Intrarosa (Endoceutics, Inc.) has received FDA approval for the treatment of women experiencing moderate-to-severe pain during sexual intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA) due to menopause. Intrarosa is the first FDA-approved product containing the active ingredient prasterone, which is also known as dehydroepiandrosterone.

The efficacy of Intrarosa, a once-daily vaginal insert, was established in two 12-week, placebo-controlled trials involving a total of 406 healthy post-menopausal women, 40 to 80 years of age, who identified moderate-to-severe pain during sexual intercourse as their most bothersome symptom of VVA. The women were randomly assigned to receive prasterone or a placebo vaginal insert. Prasterone reduced the severity of pain experienced during sexual intercourse compared with placebo.

Source: Endoceutics, November 17, 2016

Vemlidy for Hepatitis B

The FDA has approved tenofovir alafenamide 25 mg (Vemlidy, Gilead Sciences), a prodrug of tenofovir, as a once-daily treatment for adults with chronic hepatitis B virus (HBV) infection with compensated liver disease. The approval was based on positive 48-week data from two international phase 3 studies involving 1,298 treatment-naïve and treatment-experienced adults.

A total of 425 HBeAg-negative patients and 873 HBeAg-positive patients were treated with either tenofovir alafenamide or tenofovir disoproxil fumarate (TDF) (Viread, Gilead Sciences) in studies 108 and 110, respectively. HBeAg, a hepatitis B viral protein, indicates active viral replication. Both studies met their primary endpoint of noninferiority to TDF, based on the percentage of patients with plasma HBV DNA levels less than 29 IU/mL after 48 weeks of therapy.

Source: Gilead Sciences, November 10, 2016

Generic Approvals and Launches

Armodafinil Tablets

Breckenridge Pharmaceutical, Inc., and its partner Natco Pharma Ltd. have launched armodafinil tablets (CIV) in 50-mg, 150-mg, and 250-mg strengths after receiving final FDA approval. Armodafinil tablets are a generic version of Nuvigil (Cephalon, Inc.), a prescription medication indicated to improve wakefulness in adults with excessive sleepiness associated with obstructive sleep apnea, narcolepsy, or shift work disorder.

Source: Breckenridge Pharmaceutical, November 28, 2016

Metaxalone Tablets

The FDA has approved metaxalone tablets USP, 800 mg (Lannett Company), the therapeutic equivalent of Skelaxin (King Pharmaceuticals/Pfizer). Skelaxin is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions.

Source: Lannett Company, November 28, 2016

Memantine Hydrochloride Tablets

Lannett Company has secured FDA approval to market memantine hydrochloride tablets USP, 5 mg and 10 mg— the therapeutic equivalent to Namenda tablets 5 mg and 10 mg (Forest Laboratories). The product is indicated for the treatment of moderate-to-severe dementia.

Source: Lannett Company, November 14, 2016

NEW INDICATIONS

Avastin for Ovarian Cancer

The FDA has given the nod to bevacizumab (Avastin, Genentech), either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine chemotherapy, followed by bevacizumab alone, for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Previously approved indications for bevacizumab include first- or second-line treatment of patients with meta-static colorectal cancer in combination with intravenous 5–fluorouracil-based chemotherapy; second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line bevacizumab-containing regimen, in combination with fluoropyrimidine/irinotecan- or fluoropyrimidine/oxaliplatin-based chemo therapy; first-line treatment of patients with unresectable, locally advanced, recurrent, or metastatic nonsquamous, non–small-cell lung cancer in combination with carboplatin and paclitaxel chemotherapy; and treatment of metastatic renal cell carcinoma in combination with interferon alfa.

Source: Genentech, December 6, 2016

Jardiance for Diabetes Patients With CVD

The FDA has approved a new indication for empagliflozin (Jardiance, Boehringer Ingelheim) to reduce the risk of cardiovascular death in adults with type-2 diabetes (T2D) and cardiovascular disease (CVD). The FDA’s decision was based on a post-marketing study required by the agency when it approved empagliflozin in 2014 as an adjunct to diet and exercise to improve glycemic control in adults with T2D. Empagliflozin was assessed in more than 7,000 patients with T2D and CVD. In the study, empagliflozin was shown to reduce the risk of cardiovascular death compared with placebo when added to standard-of-care therapies for diabetes and atherosclerotic CVD.

Source: FDA, December 2, 2016

FluLaval Quadrivalent Vaccine

The FDA’s Center for Biologics Evaluation and Research has expanded the indication for FluLaval Quadrivalent influenza vaccine (GlaxoSmithKline) to include use in children 6 months of age and older. The vaccine was originally approved in 2013 for patients 3 years of age and older.

Source: GlaxoSmithKline, November 21, 2016

Opdivo for Head-and-Neck Cancer

The FDA has approved nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy. Nivolumab is the only immuno-oncology treatment shown in a phase 3 study to significantly extend overall survival (OS) for these patients.

In the CheckMate-141 trial, nivolumab demonstrated significantly superior OS compared with the investigators’ choice of therapy (i.e., methotrexate, docetaxel, or cetuximab), with a 30% reduction in the risk of death (hazard ratio, 0.70; P = 0.0101) and a median OS of 7.5 months compared with 5.1 months, respectively.

Nivolumab was previously approved for use in patients with non–small-cell lung cancer, metastatic melanoma, renal cell carcinoma, or classic Hodgkin’s lymphoma.

Source: Bristol-Myers Squibb, November 10, 2016

Enbrel for Pediatric Plaque Psoriasis

The FDA has approved a supplemental biologics license application for the expanded use of etanercept (Enbrel, Amgen), making it the first systemic therapy to treat pediatric patients (4–17 years of age) with chronic moderate-to-severe plaque psoriasis.

The approval was based on positive efficacy results from a 48-week, phase 3 study in which significantly more patients who received etanercept than those who received placebo achieved a Psoriasis Area and Severity Index score of at least 75—the study’s primary endpoint—at week 12 (57% versus 11%, respectively; P < 0.001); a significant difference was observed as early as week 4.

Source: Amgen, November 4, 2016

FDA REVIEW ACTIVITIES

Priority Review Designations

Avelumab for Skin Cancer

The FDA has accepted for priority review a biologics license application for avelumab (EMD Serono/Pfizer) as a proposed treatment for patients with metastatic Merkel cell carcinoma (MCC). Avelumab is an investigational, fully human anti-programmed death ligand-1 immunoglobulin G1 monoclonal antibody. If approved, it would be the first treatment indicated for metastatic MCC in the U.S.

The submission was supported by data from the JAVELIN Merkel 200 trial, a phase 2 study involving 88 patients with metastatic MCC whose disease had progressed after at least one chemo therapy treatment. Avelumab was administered at a dose of 10 mg/kg every two weeks. The patients were followed for a median of 10.4 months. An objective response (the trial’s primary endpoint) was achieved in 28 patients (32%), including eight complete responses and 20 partial responses.

Source: Merck, November 29, 2016

Keytruda for MSI-H Cancer

The FDA has accepted for review a supplemental biologics license application (sBLA) for pembrolizumab (Keytruda, Merck Oncology), an anti-programmed death-1 therapy, for the treatment of previously treated patients with advanced microsatellite instability-high (MSI-H) cancer. The FDA granted the application a priority review with a target action date of March 8, 2017.

The sBLA will be reviewed under the FDA’s accelerated approval program based on the tumor response rate and the durability of response. The FDA previously granted breakthrough therapy designations to pembrolizumab for the treatment of patients with un resectable or metastatic MSI-H colorectal or non-colorectal cancer.

Source: Merck, November 28, 2016

Midostaurin for AML

The FDA has granted priority review status to a new drug application for midostaurin (Novartis), an oral, multi-targeted kinase inhibitor, for the treatment of newly diagnosed adults with acute myeloid leukemia (AML) with an FMS-like tyrosine kinase-3 (FLT3) mutation, as well as for the treatment of patients with advanced systemic mastocytosis. In addition, a premarket approval application for a midostaurin FLT3 companion diagnostic, developed by Novartis in collaboration with Invivoscribe Technologies, was accepted for review by the FDA.

The phase 3 RATIFY trial investigated midostaurin plus standard chemotherapy versus placebo plus standard chemo-therapy in adults younger than 60 years of age with FLT3-mutated AML. Those in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in the risk of death compared with the placebo arm (hazard ratio, 0.77; P = 0.0074).

Source: Novartis, November 14, 2016

Fast-Track Designations

IFNα Kinoid Vaccine for SLE

The FDA has granted fast-track status to IFNα Kinoid in Lupus (Neovacs), an investigational vaccine for systemic lupus erythematosus (SLE). Neovacs’ research activities are focused on pathologies associated with an overproduction of endogenous cytokines. Specifically, the company is developing active immunotherapy involving the administration of an immunogenic complex involving the target cytokine (for example, interferon alfa [IFNα]) to a carrier protein. The intramuscular injection of this kinoid induces an immune response and stimulates the production of polyclonal antibodies against the target cytokines, thereby blocking cytokine overproduction and its biologic effects.

Source: Neovacs, December 7, 2016

Velusetrag for Gastroparesis

The FDA has given a fast-track designation to velusetrag (Theravance Biopharma) for the treatment of symptoms associated with idiopathic and diabetic gastroparesis. Velusetrag is an oral, once-daily investigational medication for gastrointestinal motility disorders. It is a highly selective agonist with high intrinsic activity at the human 5-hydroxytryptamine receptor 4.

An ongoing phase 2b, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial is evaluating the efficacy and safety of velusetrag in patients with diabetic (n = 100) or idiopathic (n = 100) gastroparesis. Three dosages of velusetrag (5 mg, 15 mg, and 30 mg once daily for 12 weeks) are being evaluated. The primary endpoint is the effect of velusetrag on symptoms in patients with gastroparesis.

Source: Theravance Biopharma, December 6, 2016

ASN100 for S. Aureus Pneumonia

The FDA has granted fast-track status to ASN100 (Arsanis, Inc.) for the prevention of Staphylococcus aureus pneumonia in mechanically ventilated patients who are at high risk for S. aureus pneumonia. ASN100 is a combination of two fully human monoclonal antibodies (ASN-1 and ASN-2) that collectively neutralize six important S. aureus cytotoxins associated with pneumonia pathogenesis. ASN-1 neutralizes alpha-hemolysin, a key S. aureus toxin responsible for lung epithelial cell damage, in addition to four S. aureus leukocidins responsible for lysis of human phagocytic (immune) cells. ASN-2 inactivates the remaining S. aureus leukocidin, LukGH, which is a potent human cytotoxin that is also responsible for the lysis of human phagocytes.

Source: Arsanis, December 1, 2016

DS-8201 for Metastatic Breast Cancer

The FDA has granted a fast-track designation to DS-8201 (Daiichi Sankyo Company), an investigational human epidermal growth factor receptor-2 (HER2)-targeting antibody–drug conjugate, for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after treatment with HER2-targeted therapies, including ado-trastuzumab emtansine. DS-8201 consists of a humanized anti-HER2 antibody attached by a peptide linker to a topoisomerase I inhibitor. This linker–payload combination allows a higher drug-to-antibody ratio, according to the product’s developer.

Source: Daiichi Sankyo, December 1, 2016

Tazemetostat for B-Cell Lymphoma

The FDA has granted fast-track status to tazemetostat (Epizyme, Inc.) for the treatment of patients with diffuse large B-cell lymphoma (DLBCL) with EZH2-activating mutations. Tazemetostat inhibits EZH2, a histone methyltransferase that is increasingly understood to play a role in the growth and proliferation of a number of cancers, including DLBCL, the most commonly diagnosed form of non-Hodgkin’s lymphoma.

Tazemetostat is being evaluated as monotherapy and in combination with other agents in multiple cancer indications. Phase 2 studies of tazemetostat as monotherapy are ongoing.

Source: Epizyme, November 28, 2016

Breakthrough Therapy Status

Brentuximab for Cutaneous Lymphoma

The FDA has granted a breakthrough therapy designation to brentuximab vedotin (Adcetris, Seattle Genetics, Inc.) for the treatment of patients with CD30-expressing mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL) who require systemic therapy and have received one prior systemic therapy. MF and pcALCL are the most common subtypes of cutaneous T-cell lymphoma (CTCL), accounting for more than 75% of cases of the disease. Brentuximab vedotin is an antibody–drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL.

Source: Seattle Genetics, November 10, 2016

Orphan Drug Designations

VK0214 for Adrenoleukodystrophy

The FDA has granted orphan drug status to VK0214 (Viking Therapeutics) for the treatment of patients with x-linked adrenoleukodystrophy (X-ALD). VK0214 is an investigational, orally available thyroid receptor-beta agonist that selectively modulates lipoprotein and triglyceride levels in liver tissue. This mechanism has been demonstrated to affect the expression of the genes that are relevant to the manifestation of X-ALD. In X-ALD, mutations in the ABCD1 gene lead to the accumulation of very long-chain fatty acids (VLCFAs), which is believed to be a fundamental cause of the disease. Research has shown that increasing the expression of the ABCD2 gene can counteract this process and lead to normalization of VLCFA levels.

Source: Viking Therapeutics, December 6, 2016

Cellspan Esophageal Implants

The Cellspan esophageal implant (Biostage, Inc.) has received an orphan drug designation from the FDA as a means for restoring the structure and function of the esophagus after damage due to cancer, injury, or congenital abnormalities. The patient’s own stem cells are taken from a simple adipose/fat tissue biopsy, expanded, and banked, and then seeded onto a scaffold that mimics the natural dimensions of the organ being regenerated. The biocompatible scaffold containing the stem cells is then implanted. The proprietary technology was designed to improve outcomes for patients by potentially simplifying surgical techniques and by prompting regeneration of the patient’s own esophagus.

Source: Biostage, December 1, 2016

Risankizumab for Pediatric Crohn’s Disease

The FDA has granted an orphan drug designation to risankizumab (AbbVie) for the investigational treatment of Crohn’s disease in pediatric patients. Crohn’s disease is an incurable chronic inflammatory condition of the gastrointestinal tract that can cause diarrhea, abdominal pain, and weight loss.

Source: AbbVie, November 30, 2016

PRX-OTC for Ornithine Transcarbamylase Deficiency

PRX-OTC (PhaseRx, Inc.) has received an orphan drug designation from the FDA for the treatment of patients with ornithine transcarbamylase deficiency (OTCD). OTCD is a rare liver disorder caused by an inherited single-gene deficiency that results in hyper-ammonemia and can lead to irreversible neurological impairment, coma, and death. PRX-OTC is an intracellular enzyme replacement therapy designed to replace the missing or defective enzyme in patients with OTCD, thereby correcting the disease.

Source: PhaseRx, November 28, 2016

APX001 for Fungal and Mold Infections

The FDA’s Office of Orphan Products Development has granted orphan drug status to APX001 (Amplyx Pharmaceuticals) for the treatment of invasive candidiasis, invasive aspergillosis, coccidioidomycosis, and rare mold infections caused by Scedosporium spp., Fusarium spp., and Mucorales fungi (including Mucor spp. and Rhizopus spp.). APX001 is a first-in-class small-molecule drug candidate that targets and inhibits the conserved fungal enzyme Gwt1, thereby compromising the growth of major fungal pathogens, including Candida and Aspergillus.

Source: Amplyx Pharmaceuticals, November 16, 2016

Napabucasin for Pancreatic Cancer

Napabucasin (Boston Biomedical) has received an orphan drug designation from the FDA for the treatment of patients with pancreatic cancer. This is the second such designation for napabucasin, an orally administered agent designed to inhibit cancer stemness pathways by targeting STAT3; the first designation was for gastric cancer, including gastroesophageal junction cancer.

Source: Boston Biomedical, November 14, 2016

ELX-02 for Mucopolysaccharidosis

The FDA has granted an orphan drug designation to ELX-02 (Eloxx Pharmaceuticals) for the treatment of patients with mucopolysaccharidosis type-1 (MPS-1). ELX-02 is a synthetic amino-glycoside that has been developed as a translational read-through drug for the treatment of genetic diseases caused by nonsense mutations.

MPS-1 is a chronic, progressive genetic disorder caused by an enzymatic deficiency of alpha-L-iduronidase, which disrupts the glycosaminoglycan catabolic pathway, leading to an intralysosomal accumulation of the substrates heparan sulfate and dermatan sulfate. The accumulation of these substrates disrupts the movement of intracellular molecules, resulting in the dysfunction of cells, tissues, and organs.

Source: Eloxx Pharmaceuticals, November 7, 2016

Rare Pediatric Disease Designation

VTS-270 for Niemann–Pick Disease

The FDA has granted a rare pediatric disease designation to VTS-270 (Vtesse, Inc.), an investigational drug for children with Niemann–Pick type-C1 disease (NPC). NPC is a progressive, irreversible, chronically debilitating, and ultimately lethal genetic disease.

In early 2016, the FDA granted breakthrough therapy status for VTS-270, which is currently in a pivotal phase 2b/3 clinical trial in NPC. The FDA also previously granted orphan drug status to the medication.

VTS-270 is a mixture of hydroxypropyl betacyclodextrin (HPβCD) with a specific compositional fingerprint that distinguishes it from other HPβCD mixtures.

Source: Vtesse, November 29, 2016

New Applications

Semaglutide for Type-2 Diabetes

Novo Nordisk has submitted a new drug application to the FDA for semaglutide, a glucagon-like peptide-1 (GLP-1) analogue administered once weekly for the treatment of adults with type-2 diabetes (T2D).

The submission was based on results from the SUSTAIN clinical trial program, which included eight phase 3a studies involving more than 8,000 adults with T2D. In that program, once-weekly semaglutide was administered in combination with oral antidiabetic agents and basal insulin and demonstrated statistically significant and sustained blood glucose control compared with that of sitagliptin, extended-release exenatide, once-daily insulin glargine U100, and placebo. In addition, semaglutide was associated with significantly greater reductions in mean body weight than the comparators.

Source: Novo Nordisk, December 5, 2016

Abilify Maintena for Bipolar I Disorder

The FDA has determined that the supplemental new drug application for expanded labeling of Abilify Maintena (Otsuka/Lundbeck) for the maintenance treatment of adults with bipolar I disorder is sufficiently complete to permit a substantive review. The agency has set a target action date of July 28, 2017.

Abilify Maintena, an atypical anti-psychotic, is an intramuscular depot formulation of aripiprazole. It is a sterile lyophilized powder that, when re constituted with sterile water for injection, forms an injectable suspension that can be administered monthly. The product was approved in the U.S. in 2013 for the treatment of adults with schizophrenia.

Source: Otsuka, December 1, 2016

Abuse-Deterrent Oxaydo for Pain

Egalet Corporation has submitted to the FDA a supplemental new drug application for Oxaydo (oxycodone hydrochloride, USP) tablets CII to support an abuse-deterrent label claim for the intravenous route of abuse. The application includes in vitro data demonstrating that Oxaydo resists the extraction of oxycodone and, based on its gelling properties, is more difficult to draw into a syringe compared with a non–abuse-deterrent immediate-release (IR) oxycodone comparator. Oxaydo is an IR oral formulation indicated for the management of acute and chronic moderate-to-severe pain for which the use of an opioid analgesic is appropriate.

Source: Egalet Corporation, December 1, 2016

Valbenazine for Tardive Dyskinesia

The FDA’s Psychopharmacologic Drugs Advisory Committee has agreed to review data included in the new drug application (NDA) for valbenazine (Ingrezza, Neurocrine Biosciences) for the treatment of patients with tardive dyskinesia on February 16, 2017. The FDA has granted priority review status to the NDA, with a target action date of April 11, 2017.

VMAT2 is a protein in the human brain that is primarily responsible for repackaging and transporting monoamines (dopamine, norepinephrine, serotonin, and histamine) in pre synaptic neurons. Valbenazine is a highly selective VMAT2 inhibitor that modulates dopamine release during nerve communication.

Source: Neurocrine Biosciences, November 29, 2016

OxyContin Bioequivalent

Intellipharmaceutics International, Inc., has filed a new drug application with the FDA seeking authorization to market Rexista abuse-deterrent oxycodone hydrochloride extended-release tablets in 10-mg, 15-mg, 20-mg, 30-mg, 40-mg, 60-mg, and 80-mg strengths.

Rexista is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The submission was supported by data from pivotal pharmacokinetic studies, which demonstrated that Rexista is bio-equivalent to OxyContin (oxycodone hydrochloride extended release, Purdue Pharma).

Source: Intellipharmaceutics International, November 25, 2016

Guselkumab for Plaque Psoriasis

Janssen Biotech has submitted a biologics license application to the FDA seeking approval of guselkumab for the treatment of adults with moderate-to-severe plaque psoriasis. Guselkumab is a human monoclonal antibody that targets interleukin-23, a protein that plays a key role in the development of immune-mediated inflammatory diseases.

Source: Janssen Biotech, November 17, 2016

L-Glutamine for Sickle Cell Disease

The FDA has accepted for review a new drug application for orally administered pharmaceutical-grade L-glutamine (Emmaus Life Sciences) for the treatment of patients with sickle cell disease. Data from a phase 3 study demonstrated a reduction in the frequency of sickle cell crises and hospitalizations, a reduction in cumulative days hospitalized, and a lower incidence of life-threatening acute chest syndrome in 230 adult and pediatric patients. If approved, the product would be the first potential new treatment for adults with sickle cell disease in nearly 20 years.

Source: Emmaus Life Sciences, November 8, 2016

Biosimilar Herceptin

Mylan and Biocon Ltd. have submitted a biologics license application for MYL-14010, a proposed biosimilar trastuzumab, to the FDA. The product is a proposed biosimilar to Herceptin (Genentech), which is indicated to treat certain human epidermal growth factor receptor-2-positive breast and gastric cancers. Mylan and Biocon believe it to be the first submission of a proposed biosimilar trastuzumab in the U.S.

Source: Mylan, November 8, 2016

Stivarga for Liver Cancer

Bayer has submitted a supplemental new drug application to the FDA to have its cancer medication regorafenib (Stivarga) approved for the second-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). Regorafenib, an oral multikinase inhibitor, is currently indicated for patients with metastatic colorectal cancer or locally advanced, unresectable, or metastatic gastrointestinal stromal tumors.

The submission was based on positive data from the phase 3, placebo-controlled RESORCE trial, which investigated regorafenib in 573 patients with uHCC whose disease had progressed during treatment with sorafenib (Nexavar, Bayer). The patients were randomly assigned to receive regorafenib or placebo plus best supportive care.

The study met its primary endpoint of a statistically significant improvement in overall survival (OS) with regorafenib. Median OS was 10.6 months for regorafenib compared with 7.8 months for placebo.

Source: Bayer, November 7, 2016

Complete Response Letter

Heplisav-B Vaccine

Dynavax Technologies Corporation has received a complete response letter (CRL) from the FDA regarding its biologics license application for Heplisav-B (hepatitis B vaccine, recombinant [adjuvanted]) for the immunization of adults 18 years of age and older against hepatitis B infection. The CRL seeks information on several topics, including clarification of specific adverse events of special interest; a numerical imbalance in the number of cardiac events in one study; new analyses of the integrated safety database across different time periods; and post-marketing commitments. The vaccine was previously the subject of a CRL in 2012.

Heplisav-B is an investigational hepatitis B vaccine for adults that combines hepatitis B surface antigen with a Toll-like receptor 9 agonist to enhance the immune response. The vaccine is administered in two doses over one month.

Source: Dynavax Technologies, November 14, 2016

CLINICAL TRIAL NEWS

Tagrisso for Lung Cancer

Promising results have been reported from a phase 3 study of osimertinib (Tagrisso, AstraZeneca) in the second-line treatment of patients with epidermal growth factor receptor T790M mutation-positive locally advanced or metastatic non–small-cell lung cancer. Osimertinib improved progression-free survival (PFS) by 5.7 months compared with standard platinum-based doublet chemo therapy (10.1 months versus 4.4 months, respectively; hazard ratio [HR], 0.30; P < 0.001). Moreover, in the 34% of patients with central nervous system metastases at baseline, PFS was significantly greater with osimertinib than with platinum-based doublet chemotherapy (8.5 months versus 4.2 months, respectively; HR, 0.32).

Source: AstraZeneca, December 6, 2016

Bosulif for CML

Positive results have been reported from a phase 3 comparison of bosutinib (Bosulif, Pfizer/Avillion) and imatinib as first-line treatments in patients with chronic-phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). The study met its primary endpoint of a superior major molecular response at 12 months with bosutinib compared with imatinib. Bosutinib is currently indicated in the U.S. for the treatment of adults with Ph+ CML who were resistant to or intolerant of prior therapy.

Bosutinib is an oral, once-daily tyrosine kinase inhibitor that inhibits the Bcr-Abl kinase, which promotes CML; it is also an inhibitor of Src-family kinases. Bosutinib was approved by the FDA in September 2012 for the treatment of adults with Ph+ CML who were resistant to or intolerant of prior therapy.

Source: Pfizer, December 5, 2016

Jakafi for Myelofibrosis

A pooled analysis of five-year follow-up data from the phase 3 COMFORT-I and COMFORT-II trials has suggested that earlier treatment with ruxolitinib (Jakafi, Incyte Corporation), a first-in-class Janus kinase-1 (JAK1) and JAK2 inhibitor, may result in an improved survival advantage for patients with intermediate- or high-risk myelo fibrosis compared with best available therapy or placebo. The findings showed prolonged survival in patients treated with ruxolitinib, with the risk of death reduced by 30% compared with the control groups. Ruxolitinib also showed an overall survival advantage in various patient subgroup analyses, including age, gender, disease type, risk status, JAK2V617F mutation status, baseline spleen length, anemia, white blood cell count, and platelet count.

Source: Incyte Corporation, December 4, 2016

Vonvendi for Blood Loss in Surgery

Positive results have been reported from a phase 3 trial of Vonvendi (von Willebrand factor [recombinant], Shire) to treat bleeds in elective surgical settings for adults with severe von Willebrand disease (VWD), the most common inherited bleeding disorder. Vonvendi is an on-demand recombinant treatment for adults with VWD and replaces von Willebrand factor, one of several types of proteins in the blood that are needed to facilitate proper blood clotting missing in patients with VWD. The study met its primary endpoint, indicating that Vonvendi effectively controlled bleeding and blood loss during an operation in adults undergoing major, minor, and oral elective surgical procedures. The results from this study will form the basis of a supplemental new drug application to the FDA, in which Shire will request an expanded indication for Vonvendi.

Source: Shire, December 2, 2016

Lyrica for Pediatric Epilepsy

Pfizer has announced positive results from a phase 3 study that evaluated the use of pregabalin (Lyrica) capsules CV and oral solution CV as adjunctive therapy for pediatric epilepsy patients 4 to 16 years of age with partial-onset seizures. Adjunctive treatment with pregabalin 10 mg/kg per day resulted in a statistically significant reduction in seizure frequency compared with placebo (the primary efficacy endpoint). The 12-week, double-blind, placebo-controlled, randomized, parallel-group study involved 295 pediatric patients in 18 countries.

In the United States, pregabalin is indicated for the treatment of fibromyalgia, diabetic nerve pain, spinal cord injury nerve pain, and pain after shingles in adults. The medication is also indicated for the treatment of partial-onset seizures in adults with epilepsy who take one or more drugs for seizures. Pregabalin is not approved as adjunctive therapy for pediatric epilepsy patients with partial-onset seizures.

Source: Pfizer, December 1, 2016

Psilocybin for Anxiety and Depression in Cancer Patients

When combined with psychological counseling, a single dose of a mind-altering compound contained in psychedelic mushrooms significantly lessened mental anguish in distressed cancer patients for months at a time, according to the results of a clinical study led by researchers at the New York University Langone Medical Center.

Published online in December in the Journal of Psychopharmacology, the study showed that one-time treatment with the hallucinogenic drug psilocybin—the use of which requires federal waivers because it is a banned substance— brought relief from distress that lasted for more than six months in 80% of the 29 study patients monitored, based on clinical evaluation scores for anxiety and depression.

Source: NYU Langone Medical Center, December 1, 2016

Pulmaquin for Lung Infection

Pulmaquin (Aradigm Corporation), a once-daily inhaled formulation of ciprofloxacin, has failed to meet the primary endpoint in a late-stage study involving patients with non-cystic fibrosis bronchiectasis (non-CF BE) who had chronic lung infections with Pseudomonas aeruginosa. In another study, however, Pulmaquin was deemed to have had a statistically significant benefit over placebo.

The primary endpoint in both trials was an increase in the median time to the first mild, moderate, or severe pulmonary exacerbation (PE). The key secondary efficacy endpoint in both studies was the frequency of PEs during the 48-week, double-blind treatment period.

In the ORBIT-3 trial, the median time to the first PE was 221 days in the Pulmaquin group compared with 136 days in the placebo group (P = 0.8488). Pulmaquin-treated patients showed a 13% reduction in the frequency of PEs during the 48-week treatment period compared with those given placebo (P = 0.3125).

In the ORBIT-4 trial, the median time to the first PE was 230 days in the Pulmaquin group compared with 163 days in the placebo group (P = 0.0462). In addition, there was a 37% reduction in the frequency of PEs during the 48-week treatment period in the Pulmaquin group compared with the placebo group (P = 0.0007).

Source: Aradigm Corporation, December 1, 2016

Herceptin Biosimilar For Breast Cancer

Pfizer has announced that its pivotal REFLECTIONS B3271002 trial, a comparative safety and efficacy study of PF-05280014 versus Herceptin (trastuzumab, Genentech), met its primary endpoint. PF-05280014 is a monoclonal antibody that is in development as a potential biosimilar for all approved indications of Herceptin. Currently, Herceptin is indicated for the treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer and gastric cancer.

The randomized, double-blind trial demonstrated equivalence in the primary endpoint of the objective response rates for PF-05280014 and Herceptin administered in combination with paclitaxel in first-line patients with HER2-positive metastatic breast cancer after 25 weeks of treatment.

Source: Pfizer, November 29, 2016

Cosentyx for Psoriatic Arthritis

New data have shown that secukinumab (Cosentyx, Novartis), a fully human interleukin-17A inhibitor, delivered sustained improvements in the signs and symptoms of psoriatic arthritis (PsA)—including patient-reported pain—during three years of treatment. In the first year of a three-year open-label extension study, 77% of PsA patients achieved at least 20% improvement in American College of Rheumatology response criteria. The new data also showed that response rates were consistent from year 1 (69%) to year 3 (77%).

Source: Novartis, November 14, 2016

Baricitinib for RA

New data analyses of two phase 3 studies have shown that treatment with baricitinib (Eli Lilly/Incite Corporation) resulted in improvements in rheumatoid arthritis (RA) symptoms regardless of the patients’ age, body mass index, or previous treatment with conventional synthetic disease-modifying antirheumatic drugs. At week 12, in the baricitinib 4-mg group, 67% of patients less than than 65 years of age and 68% of patients 65 years of age or older showed at least a 20% improvement according to American College of Rheumatology criteria (ACR20). In the group that received placebo, 40% of patients less than 65 years of age and 43% of patients 65 years or age or older achieved an ACR20 response.

Baricitinib is a once-daily oral selective Janus kinase-1 (JAK1) and JAK2 inhibitor currently in late-stage clinical studies for the treatment of inflammatory and autoimmune diseases.

Source: Eli Lilly, November 14, 2016

Simponi Aria for Ankylosing Spondylitis

A pivotal phase 3 study has demonstrated the efficacy of the intravenous anti-tumor necrosis factor (TNF)-alpha therapy golimumab (Simponi Aria, Janssen) in patients with active ankylosing spondylitis (AS). Data from the GO-ALIVE trial showed that 73% of patients with active AS receiving golimumab 2 mg/kg achieved the primary endpoint of at least a 20% improvement in the Assessment in Ankylosing Spondylitis criteria at week 16, compared with 26% of patients receiving placebo (P ≤ 0.001). In July 2013, golimumab received FDA approval as a 30-minute infusion for the treatment of adult patients with moderately to severely active rheumatoid arthritis in combination with methotrexate.

Source: Janssen, November 14, 2016

Long-Acting Buprenorphine For Opioid Addiction

Positive results have been reported from a pivotal phase 3, randomized, double-blind, double-dummy, active-controlled trial of weekly and monthly subcutaneous injections of buprenorphine (Braeburn Pharmaceuticals/Camurus) for the treatment of patients with moderate-to-severe opioid use disorder. Long-acting buprenorphine achieved the study’s primary endpoint of statistical noninferiority compared with daily sublingual buprenorphine/naloxone (the current standard of care) in terms of the response to treatment.

Buprenorphine maintenance therapy is currently considered the “gold standard” for the treatment of opioid use disorder, with more than one million patients receiving buprenorphine in the U.S. and Europe. Currently, most patients receiving buprenorphine take daily doses.

Source: Braeburn Pharmaceuticals, November 14, 2016

Romosozumab for Decreased Bone Mineral Density in Men

Results from the phase 3 BRIDGE trial have shown that, in men with osteoporosis, treatment with the investigational agent romosozumab (Amgen/UCB) resulted in a significant 12.1% gain in bone mineral density (BMD) at the lumbar spine compared with placebo at 12 months (the study’s primary endpoint) (P < 0.01). Both secondary endpoints were also met, with romosozumab showing a statistically significant increase in BMD at the total hip (2.5%) and the femoral neck (2.2%) at 12 months (both P < 0.01 compared with placebo). Romosozumab is a bone-forming monoclonal agent that inhibits the activity of the protein sclerostin.

Source: Amgen, November 14, 2016

Ibalizumab for HIV

A 24-week phase 3 study has confirmed the safety and efficacy results with ibalizumab (Theratechnologies, Inc./TaiMed Biologics) observed in a previously completed phase 2b trial, despite the fact that the patient population in the phase 3 investigation had higher levels of multi-drug-resistant human immunodeficiency virus-1 (HIV-1) and more advanced disease at the time of enrollment. Ibalizumab is a humanized monoclonal antibody.

The results indicated that 33 of the 40 patients (83%) met the primary endpoint of a reduction of at least 0.5 log10 in the viral load after seven days of treatment with ibalizumab. After 24 weeks of treatment, the mean reduction in the viral load was 1.6 log10, and 48% of the patients showed a viral load reduction of more than 2.0 log10.

Source: Theratechnologies, November 10, 2016

Binimetinib/Encorafenib For Melanoma

A pivotal phase 3 trial of binimetinib plus encorafenib (Array BioPharma/Pierre Fabre) in patients with BRAF-mutant melanoma has met its primary endpoint, with the combination significantly improving progression-free survival (PFS) compared with vemurafenib, a BRAF inhibitor, alone. The median PFS for patients treated with binimetinib/encorafenib was 14.9 months compared with 7.3 months for patients treated with vemurafenib (hazard ratio, 0.54; P < 0.001). Binimetinib is a late-stage small-molecule MEK inhibitor, and encorafenib is a late-stage small-molecule BRAF inhibitor, both of which target key enzymes in this pathway.

Source: Array BioPharma, November 9, 2016

Spinraza for Spinal Muscular Atrophy

Spinraza (nusinersen, Biogen/Ionis Pharma) provided a significant improvement in motor function compared with placebo (the primary endpoint) in a phase 3 study of patients with later-onset spinal muscular atrophy (SMA). SMA is characterized by the loss of motor neurons in the spinal cord and lower brain stem. This results in severe, progressive muscular atrophy and weakness. Over time, patients with the most severe form of SMA can become paralyzed and have difficulty in breathing and swallowing. Patients with SMA do not produce enough survival motor neuron (SMN) protein, which is caused by a defect in the SMN1 gene. Spinraza is an antisense oligonucleotide that alters the splicing of SMN2, a gene almost identical to SMN1, which results in the increased production of fully functional SMN protein.

Source: Biogen, November 7, 2016

Orkambi in Children With CF

Positive results have been reported from a phase 3 study of Orkambi (lumacaftor/ivacaftor, Vertex Pharmaceuticals) in children 6 through 11 years of age with cystic fibrosis (CF) who have two copies of the F508del mutation. The study met its primary endpoint of an absolute change in the lung clearance index (LCI2.5) after 24 weeks of treatment, demonstrating a statistically significant improvement in LCI2.5 among patients treated with Orkambi compared with those given placebo. At baseline, the mean LCI2.5 was 10.28. Children treated with Orkambi experienced an improvement in lung function of −1.09 compared with placebo after 24 weeks (P < 0.0001).

Source: Vertex Pharmaceuticals, November 7, 2016

Minocycline Foam for Acne

Foamix Pharmaceuticals has completed patient enrollment in two phase 3 trials designed to evaluate the efficacy and safety of FMX101, a topical 4% minocycline foam, in the treatment of patients with moderate-to-severe acne. The two pivotal studies are being conducted simultaneously, and results are expected in the first half of 2017.

A total of 961 patients were enrolled in the two trials. Patients who complete the 12-week double-blind portion of the studies will have the option to continue in a long-term open-label safety extension, which will evaluate the safety of intermittent use of FMX101 for up to an additional nine months.

Source: Foamix Pharmaceuticals, November 28, 2016

Daprodustat for Anemia Associated With Renal Disease

GlaxoSmithKline has begun a phase 3 development program investigating daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, as a treatment for anemia associated with chronic kidney disease (CKD). The program includes two clinical trials. The first trial, ASCEND-D, will enroll approximately 3,000 dialysis-dependent patients with CKD-associated anemia who are switching from an erythropoietin-stimulating agent (ESA). The second trial, ASCEND-ND, will enroll approximately 4,500 non–dialysis-dependent patients with CKD-associated anemia and will include patients who are either switching from or naïve to an ESA. For both studies, the coprimary endpoints are the time to the first occurrence of major adverse cardiovascular events and the mean change in hemoglobin levels between baseline and the efficacy period (i.e., the mean during weeks 28 to 52). The studies will assess whether daprodustat is noninferior to recombinant human erythropoietin on these endpoints.

Source: GlaxoSmithKline, November 25, 2016

DEVICE APPROVALS

TroClose1200 Trocar

The FDA has cleared the TroClose1200 (Gordian Surgical), a new trocar with an integrated closure system for suturing abdominal-wall incisions during laparoscopic surgical procedures. The device acts as both a trocar, through which surgical instruments enter the abdomen, and a device to close internal incisions made during surgery. The sutures are inserted into the tissue at the beginning of the procedure and anchored to remain in place throughout the operation, allowing the incisions to be closed quickly upon removal of the device.

Source: Gordian, December 7, 2016

Insulia Diabetes-Management Software

Paris-based company Voluntis has received FDA 510(k) clearance for the Insulia Diabetes Management Companion, a global digital device for patients with type-2 diabetes who are being treated with insulin. The prescription-only medical device works with Sanofi’s Lantus (insulin glargine injection) and Novo Nordisk’s Levemir (insulin detemir [rDNA origin] injection). A patient may use the application via a Web portal, on a smartphone, or on a tablet. The device will be available in the first half of 2017.

The Insulia device provides patients with insulin dose recommendations and educational coaching messages in response to blood glucose values and other diabetes-related data. The device also supports a variety of treatment plans and evidence-based insulin adjustment rules used in routine clinical practice.

Source: Voluntis, December 6, 2016

Xonrid Gel for Dermatitis Induced by Radiotherapy

Xonrid gel (Helsinn Integrative Care), a topical gel for radiotherapy-induced dermatitis—classified as a medical device in the European Union—has received 510(k) FDA clearance. This allows the product to be marketed in the U.S. for the management of the burning and itching associated with radiation dermatitis.

The nonsterile water-based gel forms a protective barrier on skin to increase moisture and to reduce water loss. Its contents include emollients, preservatives, skin-conditioning agents, viscosity-increasing agents, emulsifying agents, and binders. The gel is applied three times per day or as needed.

Source: Helsinn Integrative Care, December 1, 2016

PolyPlex Wound Dressing

The FDA has approved PolyPlex wound dressing (Global Health Solutions), a first-of-its-kind, petrolatum-based topical gel indicated for the management of acute and chronic wounds. The gel provides protection against bacteria, fungi, and yeasts without irritating fragile, healing tissue, according to the manufacturer. It will be available in January 2017 through McKesson Medical-Surgical.

Source: Global Health Solutions, November 28, 2016

XEN Glaucoma Treatment System

The FDA has cleared the XEN glaucoma treatment system (Allergan), consisting of the XEN45 gel stent and the XEN injector, for use in the United States. The system reduces intraocular pressure (IOP) and is indicated for the management of refractory glaucoma for which previous surgical treatment has failed or in patients with primary open-angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy. XEN is implanted through an ab-interno approach and reduces IOP by creating a new drainage channel with a permanent implant that becomes flexible.

Source: Allergan, November 22, 2016

Ofirmev IV Bag

The FDA has given the OK to a prior approval supplement (PAS) for Ofirmev (acetaminophen, Mallinckrodt Pharmaceuticals) injection available in an intra venous (IV) bag, which will provide health care providers with an additional delivery option. The PAS to the approved new drug application for Ofirmev included the addition of a new container closure and manufacturer. The polypropylene bags will be manufactured by Fresenius Kabi. Mallinckrodt anticipates product availability in the second quarter of 2017.

Ofirmev injection is the only IV formulation of acetaminophen to be approved and marketed in the United States. The FDA approved the drug in November 2010. Ofirmev is indicated for the management of mild-to-moderate pain; the management of moderate-to-severe pain with adjunctive opioid analgesics; and the reduction of fever.

Source: Mallinckrodt, November 8, 2016

Propeller Platform For Ellipta Inhaler

The FDA has cleared the Propeller platform (Propeller Health) for use with the Ellipta inhaler (GlaxoSmith-Kline). The digitally guided platform is designed to help patients and their physicians better understand asthma and chronic obstructive pulmonary disease and to help improve the symptoms and outcomes of these chronic respiratory diseases. With proprietary sensor technology, software, and services, the platform integrates information from multiple sources, including connected medications, and then uses machine intelligence to help individuals manage their condition.

Source: Propeller Health, November 7, 2016