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Drug and Device News October 2016

NEW DRUG APPROVALS

Biosimilar Etanercept (Erelzi)

The FDA has approved etanercept-szzs (Erelzi, Sandoz) for several inflammatory diseases. The product is a biosimilar to etanercept (Enbrel, Amgen), which was originally licensed in 1998.

Etanercept-szzs is administered by injection for the treatment of moderate-to-severe rheumatoid arthritis, either as a stand-alone therapy or in combination with methotrexate (MTX); moderate-to-severe polyarticular juvenile idiopathic arthritis in patients 2 years of age and older; active psoriatic arthritis, including use in combination with MTX in psoriatic arthritis patients who do not respond adequately to MTX alone; active ankylosing spondylitis; and chronic moderate-to-severe plaque psoriasis in adults 18 years of age and older who are candidates for systemic therapy or phototherapy.

Source: FDA, August 30, 2016

Afluria Quadrivalent Flu Vaccine

Afluria Quadrivalent (Seqirus) has been approved by the FDA for use in individuals 18 years of age and older. The product is an inactivated influenza vaccine indicated for active immunization against influenza disease caused by the influenza A subtype viruses and type B viruses contained in the vaccine. Both Afluria Quadrivalent and Afluria Trivalent vaccines are available in the United States for the 2016–2017 influenza season.

The traditional seasonal flu vaccine is a trivalent formula consisting of two strains of influenza A viruses and a single strain of influenza B virus. However, since 1985, two distinct lineages of influenza B virus have cocirculated with varying dominance. The use of a four-strain influenza vaccine, such as Afluria Quadrivalent, may provide protection against both B lineages, according to Seqirus.

Source: Seqirus, August 29, 2016

Troxyca ER for Pain Management

The FDA has approved Troxyca ER capsules (oxycodone hydrochloride and naltrexone hydrochloride, Pfizer) 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.

Troxyca ER extended-release capsules contain pellets that consist of oxycodone hydrochloride, an opioid agonist, which surround sequestered naltrexone hydrochloride, an opioid antagonist. When taken orally as directed, the naltrexone is intended to remain sequestered, and patients receive oxycodone in an extended-release manner. Studies have shown that when the pellets are crushed, the sequestered naltrexone is released and is available to counteract the effects of oxycodone. The drug is classified as a Schedule II substance.

Source: Pfizer, August 19, 2016

Generic Approvals

Doxylamine/Pyridoxine Delayed Release Tablets

The FDA has approved the sale of doxylamine succinate/pyridoxine hydrochloride (10 mg/10 mg) delayed release tablets by Actavis Laboratories FL, Inc. (now part of Teva Pharmaceuticals). This is the first generic version of Diclegis (Duchesnay, Inc.), which is used for the treatment of nausea and vomiting during pregnancy in women who do not respond to conservative management.

Source: FDA, August 19, 2016

Zolpidem Tartrate Sublingual Tablets

The FDA has ruled that zolpidem tartrate sublingual tablets, 5 mg and 10 mg, can be marketed by Par Formulations (now part of Endo International, PLC) and Mylan Pharmaceuticals, Inc. The agency says these are the first generic versions of Edluar sublingual tablets (Meda Pharmaceuticals, Inc.), which are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation.

Source: FDA, August 1 and 8, 2016

Telmisartan Tablets

Jubilant Life Sciences has received final approval of its abbreviated new drug application for telmisartan tablets USP, 20 mg, 40 mg, and 80 mg—the generic version of Micardis (Boehringer Ingelheim), which is used to treat hypertension.

Source: Jubilant Life Sciences, August 24, 2016

Ranitidine Tablets

India-based Strides Shasun, Ltd., has received approval from the FDA for ranitidine tablets USP, 150 mg and 300 mg. The product is being marketed in the U.S. by Strides Pharma, Inc.

Ranitidine is used to treat ulcers of the stomach and intestines and to prevent them from returning after they have healed. The drug is also indicated for certain stomach and throat problems. Ranitidine is a histamine H2-receptor antagonist, commonly known as an acid reducer.

Source: Strides Shasun, August 24, 2016

Temozolomide Capsules

The FDA has granted final approval for temozolomide capsules (Amerigen Pharmaceuticals/Stason Pharmaceuticals) in 5-mg, 20-mg, 100-mg, 140-mg, 180-mg, and 250-mg strengths. The drug, a generic version of Temodar (Merck), is indicated for newly diagnosed glioblastoma multiforme and for refractory anaplastic astrocytoma. Generic temozolomide has been launched and is being manufactured by Stason.

Source: Amerigen Pharmaceuticals, August 18, 2016

NEW INDICATIONS

Blincyto for ALL

The FDA has approved a supplemental biologics license application for blinatumomab (Blincyto, Amgen) to include new data supporting the treatment of pediatric patients with Philadelphia chromosome-negative (Ph−) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). This indication was awarded under accelerated approval, and continued approval may be contingent on verification of clinical benefit in subsequent trials.

Blinatumomab is a bispecific CD19-directed CD3 T-cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and on CD3 expressed on the surface of T cells.

Source: Amgen, September 1, 2016

Trokendi XR for Migraine and Seizures

The FDA has granted tentative approval to a supplemental new drug application (sNDA) requesting a label expansion for Trokendi XR (extended-release topiramate, Supernus Pharmaceuticals) to include the prophylaxis of migraine headache in adults.

The approval of the sNDA is tentative because the FDA has determined that the drug meets all of the required quality, safety, and efficacy standards for approval but is subject to pediatric exclusivity, which expires in March 2017. Final approval may not become effective until this exclusivity period has expired.

In addition, the FDA has granted final approval to expand the label for Trokendi XR for monotherapy of partial-onset seizures to include adults and pediatric patients 6 years of age and older, rather than 10 years of age and older.

Source: Supernus Pharmaceuticals, August 19, 2016

FDA REVIEW ACTIVITIES

Priority Review Status

Keytruda for NSCLC

The FDA has accepted for priority review a supplemental biologics license application for pembrolizumab (Keytruda, Merck), an anti-programmed death-1 (PD-1) therapy, for the first-line treatment of patients with advanced non–small-cell lung cancer (NSCLC) whose tumors express programmed death ligand-1 (PD-L1), with a target action date of December 24, 2016. In addition, the FDA granted a breakthrough therapy designation for this indication.

Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.

Source: Merck, September 7, 2016

Rucaparib for Ovarian Cancer

The FDA has accepted a new drug application (NDA) for accelerated approval of rucaparib (Clovis Oncology) and has granted priority review status to the application with a Prescription Drug User Fee Act action date of February 23, 2017. Rucaparib is an oral, small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP)-1, -2, and -3.

In June 2016, Clovis completed its NDA submission of rucaparib for the treatment of advanced ovarian cancer in patients with deleterious BRCA-mutated tumors inclusive of both germline and somatic BRCA mutations (as detected by an FDA-approved test), and who have been treated with two or more chemotherapies. Rucaparib was granted breakthrough therapy status for the proposed indication in April 2015.

Source: Clovis Oncology, August 23, 2016

Fast-Track Designation

AZD3293 for Alzheimer’s Disease

The FDA has granted a fast-track designation for the development program in Alzheimer’s disease (AD) of AZD3293 (Eli Lilly/AstraZeneca), an oral beta secretase-cleaving enzyme (BACE) inhibitor currently in phase 3 clinical trials.

AZD3293 has been shown to reduce levels of amyloid beta in the cerebrospinal fluid of people with AD and in healthy volunteers. The progression of AD is characterized by the accumulation of amyloid plaque in the brain. BACE is an enzyme associated with the development of amyloid beta. The inhibition of BACE is expected to prevent the formation and build-up of amyloid plaque, which in turn may help slow the progression of AD.

Source: Eli Lilly, August 22, 2016

Breakthrough Therapy Status

SL-401 for Dendritic-Cell Neoplasm

The FDA has awarded breakthrough therapy status to SL-401 (Stemline Therapeutics), a targeted therapy directed at the interleukin-3 receptor, for the treatment of patients with blastic plasmacytoid dendritic-cell neoplasm (BPDCN).

A phase 2, potentially pivotal trial is assessing SL-401 in patients with BPDCN. Data from this ongoing study have demonstrated high overall response rates with multiple complete responses, according to Stemline. Patients are being followed for response duration and outcomes.

Source: Stemline Therapeutics, August 24, 2016

Intranasal Esketamine for Depression

The FDA has granted a breakthrough therapy designation for intranasal esketamine (Janssen), an investigational antidepressant medication, for the indication of major depressive disorder (MDD) with an imminent risk of suicide. If approved by the FDA, esketamine would be one of the first new approaches to treat MDD available to patients in the last 50 years.

Esketamine for intranasal administration is a noncompetitive and subtype non-selective activity-dependent N-methyl-D-aspartate receptor antagonist.

Source: Janssen, August 16, 2016

Orphan Drug Designations

TXA127 for Genetic Skin Disorder

Tarix Orphan LLC has received an orphan drug designation from the FDA for TXA127 as a potential treatment for a rare genetic skin disorder—recessive dystrophic epidermolysis bullosa (RDEB). TXA127, a pharmaceutical formulation of the natural angiotensin (1–7) peptide, interferes with the transforming growth factor-beta pathway, which is involved in the pathophysiology of RDEB, as well as that of several other serious orphan diseases, including Marfan syndrome and muscular dystrophy. Preclinical studies with TXA127 have demonstrated its ability to reduce the fusion of digits, a symptom in RDEB mice that is analogous to the “mitten” deformity common in patients with severe RDEB.

Source: Tarix Orphan, September 7, 2016

NovaDerm Cultured Skin Substitute

The FDA has granted orphan drug status to NovaDerm cultured skin substitute (Regenicin, Inc.) for the treatment of burns requiring skin grafting. NovaDerm is believed to be the only autologous cultured skin substitute prepared from the patient’s own skin cells that consists of both epidermal and dermal layers.

With the NovaDerm system, a small section of the patient’s skin is harvested and is grown to graft an area more than 100 times its size within four weeks. These living tissues are intended to form permanent skin grafts that will not be rejected by the patient’s immune system.

Source: Regenicin, August 29, 2016

BTT1023 for Liver Disease

The FDA has granted an orphan drug designation for BTT1023 (Biotie Therapies Corp.) for the treatment of patients with primary sclerosing cholangitis (PSC). PSC is a chronic, progressive fibrotic liver disease for which there is no FDA-approved treatment.

BTT1023 is a fully human monoclonal antibody targeting vascular adhesion protein-1. It is being studied as a treatment for PSC in a phase 2a study in the United Kingdom. Interim results are expected in the first half of 2017.

Source: Biotie Therapies, August 26, 2016

Ublituximab for Neuromyelitis Disorders

Ublituximab (TG Therapeutics), a glycoengineered anti-CD20 monoclonal antibody, has received orphan drug status for the treatment of patients with neuromyelitis optica and neuromyelitis optica spectrum disorder. There are no FDA-approved treatments for these disorders.

Source: TG Therapeutics, August 26, 2016

Dusquetide for Macrophage Activation Syndrome

The FDA has granted an orphan drug designation to dusquetide (Soligenix, Inc.) for the treatment of patients with macrophage activation syndrome. Dusquetide was previously granted orphan drug status for the treatment of patients with acute radiation syndrome. Dusquetide is an innate defense regulator (IDR)—a new class of short, synthetic peptides that accelerate bacterial clearance and the resolution of tissue damage while modulating inflammation after exposure to a variety of agents, including bacterial pathogens, trauma, radiation, and chemotherapy. IDRs have no direct antibiotic activity but, by modulating the host’s innate immune-system responses, they can increase survival after infections with bacterial gram-negative and gram-positive pathogens.

Source: Soligenix, August 18, 2016

ZW33 for Ovarian Cancer

The FDA has granted an orphan drug designation for the investigational product ZW33 (Zymeworks, Inc.) for the treatment of ovarian cancer. ZW33 is a drug-conjugated version of ZW25 that is currently in preparation for an investigational new drug filing in early 2017. Both products target cancers expressing human epidermal growth factor receptor-2.

Source: Zymeworks, August 18, 2016

Complete Response Letter

AndexXa for Reversal Of Anticoagulation

Portola Pharmaceuticals has received a complete response letter from the FDA regarding its biologics license application for andexanet alfa (AndexXa), a modified human factor Xa molecule. The FDA requested that Portola provide additional information primarily related to manufacturing. The agency also asked for additional data to support the inclusion of edoxaban and enoxaparin on the label.

Andexanet alfa is in development for patients treated with a direct (apixaban [Eliquis, Bristol-Myers Squibb/Pfizer], rivaroxaban [Xarelto, Janssen], or edoxa-ban [Savaysa, Daiichi Sankyo]) or indirect (enoxaparin [Lovenox, Sanofi-Aventis]) factor Xa inhibitor when the reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding. There is no FDA-approved antidote for factor Xa inhibitors.

Source: Portola Pharmaceuticals, August 18, 2016

Advisory Committee Meeting

Solithromycin for Pneumonia

The FDA’s Antimicrobial Drugs Advisory Committee has scheduled a meeting on November 4 in Silver Spring, Maryland, to discuss the safety and efficacy of solithromycin (Cempra, Inc./Merck) for the treatment of patients with community-acquired bacterial pneumonia (CABP).

Solithromycin is a next-generation macrolide antibiotic with activity against most macrolide-resistant CABP pathogens. The FDA has set action dates of December 27 and December 28, respectively, for the product’s oral and intravenous formulations.

Source: Cempra, August 30, 2016

New or Revised Applications

Darzalex for Multiple Myeloma

Janssen Biotech has submitted a supplemental biologics license application for daratumumab (Darzalex) to the FDA. The application seeks to expand the current indication, using daratumumab in combination with lenalido-mide (an immunomodulatory agent) and dexamethasone, or with bortezomib (a proteasome inhibitor [PI]) and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Daratumumab, a human CD38-directed monoclonal antibody, won breakthrough therapy status for this pending indication in July 2016.

Daratumumab is currently indicated for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent.

Source: Janssen Biotech, August 18, 2016

L-Glutamine for Sickle Cell Disease

Emmaus Life Sciences has submitted a new drug application (NDA) to the FDA requesting marketing approval for its orally administered pharmaceutical-grade L-glutamine treatment for patients with sickle cell disease. The NDA represents the first potential treatment for pediatric patients with sickle cell disease and the first potential new treatment in nearly 20 years for adult patients. Emmaus requested a priority review of the application.

Source: Emmaus Life Sciences, September 8, 2016

Ozenoxacin Cream for Impetigo

The FDA has accepted for review a new drug application for ozenoxacin cream 1% (Medimetriks Pharmaceuticals), a nonfluorinated quinolone in development for the treatment of impetigo. The Prescription Drug User Fee Act date for the completion of the agency’s review is June 22, 2017.

In two phase 3 studies, ozenoxacin demonstrated superior bacteriological cure compared with placebo as early as visit 2 (days 3 to 4) and showed excellent antibacterial activity against a broad range of bacteria. The studies indicated that ozenoxacin was safe and well tolerated in both adult and pediatric populations (2 months of age and older).

Source: Medimetriks Pharmaceuticals, August 31, 2016

Edaravone for ALS

The FDA has accepted a new drug application for edaravone (Mitsubishi Tanabe Pharma Corporation), an intravenous treatment for patients with amyotrophic lateral sclerosis (ALS). A decision on the application is expected in June 2017. If approved, the medication will be commercialized under the brand name Radicava through MT Pharma America, Inc.

Edaravone is a free radical scavenger that relieves the effects of oxidative stress—a factor in the onset and progression of ALS. Oxidative stress is thought to be an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects. Patients with ALS show consistent increases in oxidative stress biomarkers.

Source: Mitsubishi Tanabe Pharma, August 30, 2016

CSL830 for Angioedema Attacks

The FDA has accepted for review a biologics license application for low-volume subcutaneous C1-esterase inhibitor (C1-INH) replacement therapy, CSL830 (CSL Behring), as prophylaxis to prevent hereditary angioedema (HAE) attacks. HAE is a rare genetic disorder caused by a deficiency of C1-INH, one of the proteins that work with the body’s immune system to control inflammation. Symptoms of HAE include episodes of swelling in the face, abdomen, larynx, and extremities, and the disorder can be fatal if untreated.

Source: CSL Behring, August 30, 2016

Brigatinib for Lung Cancer

Ariad Pharmaceuticals has completed its rolling submission of a new drug application (NDA) for brigatinib, an investigational anaplastic lymphoma kinase (ALK) inhibitor. The company is seeking marketing approval of brigatinib from the FDA for the treatment of patients with metastatic ALK-positive non–small-cell lung cancer who are resistant to or intolerant of crizotinib (Xalkori, Pfizer/EMD Serono). The company has also requested priority review of the application, which, if granted, would allow the approval of brigatinib eight months after the NDA submission, as opposed to 12 months for a standard review.

Source: Ariad Pharmaceuticals, August 30, 2016

Insulin Glargine/Lixisenatide Pen for Diabetes

Sanofi has submitted updated information on a pen delivery device as part of its new drug application (NDA) for the investigational once-daily, fixed-ratio combination of basal insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide for the treatment of adults with type-2 diabetes. The additional information, submitted at the FDA’s request, constitutes a major amendment to the NDA, resulting in an extension of the Prescription Drug User Fee Act goal date by three months to November 2016.

On May 25, 2016, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 12 to two in favor of approval of the NDA for the fixed-ratio combination.

Source: Sanofi, August 19, 2016

CLINICAL TRIAL NEWS

JCAR014 for Non-Hodgkin’s Lymphoma

Researchers at the Fred Hutchinson Cancer Research Center have reported data from an early-phase study of patients with advanced non-Hodgkin’s lymphoma who received JCAR014 (Juno Therapeutics), a chimeric antigen receptor (CAR) T-cell treatment, and chemotherapy. CAR T cells consist of the patient’s own immune cells that are genetically engineered to better identify and kill cancer cells.

Half of the 18 patients who were evaluable for efficacy after receiving CAR T cells and the chemotherapy agents fludarabine and cyclophosphamide experienced a complete response, which compared favor-ably with the 8% complete response rate in patients who received JCAR014 plus cyclophosphamide-based chemotherapy without fludarabine.

Source: Juno Therapeutics, September 7, 2016

Naldemedine for OIC

Positive results have been reported from a 52-week, placebo-controlled, phase 3 study (COMPOSE III) of naldemedine (Shionogi), an investigational, once-daily, oral, peripherally acting mu-opioid receptor antagonist for the treatment of opioid-induced constipation (OIC) in patients with chronic non-cancer pain (CNCP). Treatment with naldemedine demonstrated a statistically significant improvement in the frequency of bowel movements per week at each time point measured throughout the study compared with placebo (P ≤ 0.0001).

The FDA has accepted a new drug application for naldemedine with the proposed indication of OIC in adults with CNCP. The target action date under the Prescription Drug User Fee Act is March 23, 2017.

Source: Shionogi, September 7, 2016

Lasmiditan for Migraine

A pivotal phase 3 study of lasmiditan (CoLucid Pharmaceuticals) has achieved its primary and key secondary efficacy endpoints in patients with migraine headache pain. Twenty-eight percent and 32% of patients treated with lasmiditan 100 mg or 200 mg, respectively, were migraine headache pain free at two hours after dosing compared with 15% of placebo-treated patients (P < 0.001 for both lasmiditan groups). Similarly, in both lasmiditan groups, 41% of patients were free of the most bothersome associated symptom of migraine (i.e., nausea, phonophobia, or photophobia) at two hours after dosing compared with 30% of the placebo-treated group (P < 0.001).

Lasmiditan selectively targets 5-hydroxy tryptamine 1F (5-HT1F) receptors expressed in the trigeminal pathway.

Source: CoLucid Pharmaceuticals, September 6, 2016

Fostamatinib for Thrombocytopenia

Fostamatinib (Rigel Pharmaceuticals), an oral investigational spleen tyrosine kinase inhibitor, has met the primary endpoint in the first of two phase 3, double-blind studies involving adults with chronic/persistent immune thrombocytopenia. Eighteen percent of patients receiving fostamatinib achieved a stable platelet response compared with none receiving placebo (P = 0.0261). Results from the second phase 3 study are expected in October or November 2016. Rigel plans to submit a new drug application for fostamatinib to the FDA in the first quarter of 2017.

Source: Rigel Pharmaceuticals, August 30, 2016

Pacritinib for Myelofibrosis

Mixed results were reported from a phase 3 trial comparing pacritinib (CTI BioPharma Corp.), an investigational oral multikinase inhibitor, with physician-specified best available therapy (BAT) for the treatment of patients with myelofibrosis whose platelet counts were less than 100,000/mcL—a patient population with high-risk advanced disease.

The PERSIST-2 trial met one of its co primary endpoints, showing a statistically significant response rate in spleen volume reduction in the patients treated with pacritinib compared with BAT (P < 0.01). The other coprimary endpoint of a reduction of greater than 50% in the total symptom score compared with BAT (P = 0.0791) was not met.

In February, the FDA placed studies of pacritinib on full clinical hold based on interim survival results from the PERSIST-2 trial. In the study’s early data, deaths resulting from intracranial hemorrhage, cardiac failure, and cardiac arrest were reported in pacritinib-treated patients.

Source: CTI BioPharma, August 29 and February 9, 2016

BioChaperone PDGF for Diabetic Foot Ulcers

Disappointing results have been reported from a phase 3 trial of Bio-Chaperone PDGF (Adocia) in the treatment of diabetic foot ulcers. In the study, which was conducted in India, BioChaperone PDGF did not meet the primary endpoint of a statistically significant improvement over placebo in complete wound closure after 20 weeks of treatment.

The randomized, double-blind, multi center outpatient study enrolled 252 patients with chronic diabetic foot ulcers. In addition to standard of care, the patients were treated every two days for a maximum of 20 weeks with either a spray containing BioChaperone PDGF or a placebo saline spray.

Source: Adocia, August 25, 2016

Siponimod for Multiple Sclerosis

A phase 3 study evaluating the efficacy and safety of oral, once-daily siponimod (BAF312, Novartis) in patients with secondary progressive multiple sclerosis (SPMS) has met its primary endpoint of a reduction in the risk of disability progression compared with placebo. The study represents the largest randomized, controlled trial in SPMS to date.

Siponimod is a selective modulator of specific types of the sphingosine-1-phosphate receptor. This receptor is commonly found on the surface of specific cells in the central nervous system (CNS) that are responsible for causing the CNS damage that drives the loss of function in SPMS. Siponimod enters the brain and, by binding to these specific receptors, may prevent the activation of these harmful cells, helping to reduce the loss of physical and cognitive function associated with SPMS.

Source: Novartis, August 25, 2016

Keyzilen for Tinnitus

Disappointing results were reported from a phase 3 study of Keyzilen (Auris Medical Holding AG) in patients with acute inner-ear tinnitus. The study did not meet its two coprimary efficacy endpoints of statistically significant changes in tinnitus loudness and tinnitus burden compared with placebo.

Keyzilen is a small-molecule N-methyl-D-aspartate (NMDA) receptor antagonist formulated in a biocompatible gel for intratympanic injection. Evidence suggests that NMDA receptors in the cochlea play a major role in the occurrence of tinnitus after acute injury to the inner ear, such as from exposure to excessive noise, infections, disturbances in the inner-ear blood supply, or the administration of certain ototoxic drugs.

Source: Auris Medical, August 18, 2016

Buprenorphine Monthly Depot For Opioid Use Disorder

Positive results have been reported from a pivotal phase 3 study of RBP-6000 (buprenorphine monthly depot, Indivior PLC), an investigational drug for the treatment of opioid use disorder as part of a complete treatment plan that includes counseling and psychosocial support. If RBP-6000 receives FDA approval within the assumed six-month priority review timeline, a marketing authorization could be granted in the fourth quarter of 2017.

RBP-6000 is a buprenorphine sustained- release formulation using Indivior’s Atrigel delivery system, which consists of a polymeric solution of a biodegradable poly-(DL-lactide-co-glycolide) co-polymer dissolved in N-methyl pyrrolidone (NMP), a water-miscible biocompatible solvent. After subcutaneous injection, NMP diffuses out of the polymer matrix and the polymer precipitates, trapping the drug inside and forming an amorphous solid depot in situ. The depot releases buprenorphine over a one-month period by diffusion as the polymer biodegrades.

Source: Indivior, August 17, 2016

Abaloparatide for Osteoporosis

Positive results have been announced from a phase 3 study of self-administered subcutaneous abaloparatide (Radius Health, Inc.) for the treatment of postmenopausal women with osteoporosis. The study showed that patients treated with daily abaloparatide for 18 months had a significantly greater reduction in the incidence of new vertebral fractures (P < 0.001) and nonvertebral fractures (P = 0.049) compared with placebo.

Abaloparatide is a synthetic peptide that engages the parathyroid hormone 1 receptor. It was designed for the potential treatment of women with postmenopausal osteoporosis who are at an increased risk for fractures.

Source: Radius Health, August 16, 2016

Custirsen for Prostate Cancer

OncoGenex Pharmaceuticals has announced the results from the final analysis of its phase 3 AFFINITY study of custirsen in men with metastatic castration-resistant prostate cancer whose disease had progressed after treatment with docetaxel. The international, randomized, open-label trial did not meet its primary endpoint of demonstrating a statistically significant improvement in overall survival for patients treated with custirsen in combination with cabazitaxel/prednisone compared with cabazitaxel/prednisone alone.

Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer by disabling a fundamental cellular repair mechanism used by tumor cells.

Source: OncoGenex, August 16, 2016

VX-661/Ivacaftor For Cystic Fibrosis

Based on a futility analysis conducted by an independent data safety monitoring board (DSMB), Vertex Pharmaceuticals has terminated a phase 3 study of VX-661 and ivacaftor in subjects with cystic fibrosis (CF) with one copy of the F508del mutation and one copy of a mutation that results in minimal CF transmembrane conductance regulator protein function (F508del het/min).

The DSMB conducted a planned interim futility analysis after at least eight weeks of dosing to determine whether to stop the study or continue enrollment. The analysis showed that the combination of VX-661 and ivacaftor did not provide a prespecified improvement in lung function.

The study findings suggest that a triple combination regimen may provide this group of CF patients with the best chance of obtaining a meaningful clinical benefit, according to Vertex.

Source: Vertex Pharmaceuticals, August 15, 2016

Sublingual Sufentanil For ER Pain

Positive results have been reported from a phase 3, single-arm, open-label study of sufentanil sublingual tablets, 30 mcg (ARX-04, AcelRx Pharmaceuticals) in patients who presented to the emergency room (ER) with moderate-to-severe acute pain associated with trauma or injury. The 76 adults treated with sublingual sufentanil experienced a mean reduction in pain intensity of 2.9 from a baseline value of 8.1—a 35% reduction—on a 0 to 10 numeric rating scale at 60 minutes.

ARX-04 is a noninvasive investigational product candidate consisting of 30-mcg sufentanil tablets delivered sublingually via a disposable, prefilled, single-dose applicator.

Source: AcelRx Pharmaceuticals, August 15, 2016

Baremsis for PONV

Positive results have been reported from a pivotal phase 3 study of low-dose amisulpride injection (Baremsis, Acacia Pharma Group) for the treatment of established postoperative nausea and vomiting. In Europe, amisulpride is indicated for the management of psychoses and is given at high doses in oral form. The treatment is not available for any use in the United States.

In the pivotal trial, two doses of amisulpride, a dopamine D2/D3 antagonist antiemetic, significantly improved (P < 0.025) the complete response rate compared with placebo in patients with established nausea and/or vomiting after surgery who had not received prophylactic antiemetics. A complete response was defined as no recurrence of vomiting or a need for further antiemetic rescue within 24 hours after treatment.

Source: Acacia Pharma Group, August 12, 2016

Somavaratan for Pediatric GHD

Enrollment has been completed in the phase 3 VELOCITY trial of somavaratan (Versartis, Inc.) in pediatric growth hormone deficiency (GHD). Somavaratan is a novel, long-acting form of recombinant human growth hormone (rhGH). The trial is designed to demonstrate the non-inferiority of twice-monthly somavaratan compared with daily rhGH in pediatric patients with GHD. A total of 137 patients will be followed for the primary endpoint of height velocity at 12 months, as well as for safety and pharmacodynamic secondary endpoints. Preliminary results are expected in the third quarter of 2017.

Source: Versartis, August 22, 2016

Dolutegravir/Lamivudine For HIV-1

ViiV Healthcare has initiated a phase 3 clinical trial program to support regulatory filing for a two-drug regimen of dolutegravir (Tivicay) and lamivudine (Epivir) as a treatment for human immunodeficiency virus (HIV)-1 infection in adults who have not received prior antiretroviral therapy.

Dolutegravir is an integrase strand transfer inhibitor for use in combination with other antiretroviral agents for the treatment of HIV infection. Integrase inhibitors block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection.

Lamivudine is a nucleoside analogue used in combination with other antiretroviral agents for the treatment of patients with HIV infection.

Source: ViiV Healthcare, August 16, 2016

TransCon Growth Hormone

Ascendis Pharma has initiated a global phase 3 study of TransCon growth hormone in children with growth hormone deficiency (GHD). The company decided to conduct the study after holding discussions with the FDA and other regulatory agencies worldwide.

The TransCon growth hormone trial is a randomized, open-label, active-controlled registration study designed to enroll approximately 150 children with untreated GHD. The patients will receive either once-weekly TransCon growth hormone (0.24 mg/kg/week) or daily injections of somatropin (Genotropin, Pfizer) at 34 mcg/kg/day (0.24 mg/kg/week). The study’s primary endpoint is height velocity after 12 months of treatment.

Source: Ascendis Pharma, August 12, 2016

Voclosporin for Lupus Nephritis

Mixed results have been reported from a phase 2b trial of voclosporin (Aurinia Pharmaceuticals) in patients with active lupus nephritis (LN). The trial achieved its primary endpoint, demonstrating a significantly greater complete remission (CR) rate in patients treated with voclosporin 23.7 mg twice daily plus current standard of care compared with placebo plus standard of care (P = 0.045). However, 13 deaths occurred during the six-month study—12 in voclosporin-treated patients.

Aurinia Pharmaceuticals’ stock dropped on news of the patients’ deaths and the unexpectedly low response rates. The company explained that the deaths were due to the severe underlying nature of LN and not to its drug, even though only one of the 13 deaths occurred during placebo treatment.

Sources: Aurinia Pharmaceuticals and FierceBiotech, August 15, 2016

Venclexta for AML

Patients with acute myelogenous leukemia (AML) whose disease had relapsed or was resistant to chemotherapy and those who were unable to tolerate chemotherapy have shown clinical responses to venetoclax (Venclexta, AbbVie/Genentech), with complete remissions in some, according to phase 2 data published in Cancer Discovery. Venetoclax is a small-molecule B-cell lymphoma 2 homology 3 mimetic.

The investigators enrolled 32 adults (median age, 71 years) with AML into a multicenter, single-arm trial evaluating oral venetoclax (800 mg/day). Twenty-six patients received at least four weeks of therapy. The overall response rate was 19%; two patients experienced a complete response (CR), and four had a CR with incomplete blood-count recovery. The median duration of therapy in responders was 144.5 days, and the median duration of CRs was 48 days. All of the patients discontinued therapy because of progressive disease, an adverse event, or for other reasons.

In April 2016, the FDA approved venetoclax for the treatment of certain patients with chronic lymphocytic leukemia. It is not indicated for patients with AML.

Source: American Association for Cancer Research, August 12, 2016

Tazemetostat for Mesothelioma

An international phase 2 study is evaluating tazemetostat (Epizyme, Inc.) for the treatment of adults with mesothelioma characterized by BRCA1-associated protein-1 loss-of-function. Tazemetostat is a first-in-class, small-molecule enhancer of zeste homolog 2 (EZH2) inhibitor. Aberrant EZH2 activity results in mis-regulation of genes that control cell proliferation and has been associated with human cancers.

The 12-week, open-label trial will evaluate tazemetostat as monotherapy in a total of 67 patients at sites in the United States, the United Kingdom, and France. Tazemetostat is orally administered at a dosage of 800 mg twice daily.

Source: Epizyme, August 12, 2016

BCX7353 for Angioedema

BioCryst Pharmaceuticals is conducting a two-part, phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of BCX7353 as a preventive treatment to eliminate or reduce the frequency of angioedema attacks in patients with hereditary angioedema (HAE). Up to 50 patients will be enrolled.

BCX7353 is a once-daily, selective inhibitor of plasma kallikrein in development for the prevention of angioedema attacks in patients with HAE.

In part 1 of the study, patients with HAE will be randomly assigned to receive either oral BCX7353 (350 mg) once daily or placebo once daily for four weeks. In part 2, 14 additional patients with HAE will be randomly assigned to receive BCX7353 (250 mg) once daily (n = 6), BCX7353 (125 mg) once daily (n = 6), or placebo once daily (n = 2). The trial’s primary efficacy endpoint is the number of angioedema attacks. The attack rate per week, counts of attacks, the proportion of subjects with no attacks, and the number of attack-free days will also be analyzed.

Source: BioCryst Pharmaceuticals, August 12, 2016

DEVICE APPROVALS

Angel Catheter for Pulmonary Embolism

The FDA has granted 510(k) clearance for the Angel catheter (Bio2 Medical), which includes a first-ever prophylactic indication for a medical device to protect critically ill patients at high risk for pulmonary embolism (PE) and contra indicated for anticoagulation. The catheter provides an alternative to inferior vena cava (IVC) filters for PE protection. The device is designed for bedside placement, without the need for fluoroscopic guidance, and can be retrieved once it is no longer indicated.

The Angel catheter has a temporary IVC filter that is permanently attached to a central venous catheter. The catheter has been designed to reduce the rates of PE-related morbidity and mortality by trapping clinically significant pulmonary emboli.

Source: Bio2 Medical, August 24, 2016

Transcatheter Heart Valves

The FDA has approved an expanded indication for the Sapien XT and Sapien 3 transcatheter heart valves (Edwards Lifesciences) for patients with aortic valve stenosis who are at intermediate risk of death or complications associated with open-heart surgery. These devices were previously approved for use only in patients at high or greater risk for death or complications during surgery.

As part of the approval, the FDA is requiring the manufacturer to conduct a post-approval study to follow the patients treated with either device for 10 years to further monitor safety and effectiveness.

Source: Edwards Lifesciences, August 18, 2016

DEVICE SAFETY ISSUES

Aortic Valve Insertion Device Linked to 19 Deaths

Minnesota-based heart device maker Medtronic PLC has warned doctors worldwide to be especially careful when using the EnVeo R delivery system to insert the Evolut R aortic valve after 19 patients died from severe blood-vessel trauma, according to an article in the Minneapolis Star Tribune. Medtronic also informed doctors that it is voluntarily updating its instructions for using the EnVeo R delivery system.

Technically, the FDA classified Medtronic’s announcement as a medium-severity (class II) recall, but no product is actually being sent back to the company because the device isn’t considered defective. Medtronic transcatheter valves that have been successfully implanted are not affected by the recall.

Source: Minneapolis Star Tribune, August 18, 2016

FDA Warning on Syringe Pumps

The FDA has informed health care professionals that when using programmable syringe pumps to infuse therapies at low rates (e.g., less than 5 mL per hour, and especially at flow rates of less than 0.5 mL per hour), a lack of flow continuity (i.e., an inconsistent rate of delivery) can result in serious clinical consequences, including delayed therapy, overinfusion, or underinfusion.

Reports of serious adverse events, such as abnormal or unstable blood pressure, anxiety from loss of sedation, and increased pain indicators in critically ill infants, have been associated with the lack of flow continuity. The FDA believes that these concerns may extend to all programmable syringe pumps while infusing at low rates. Based on current information, the FDA believes that the overall benefits of programmable syringe pumps outweigh their risks.

Source: FDA, August 25, 2016

OTHER DEVICE NEWS

NeuroBlate for Glioblastoma Multiforme

The FDA has approved an investigational device exemption (IDE) to evaluate the NeuroBlate system (Monteris Medical) in patients with newly diagnosed glioblastoma multiforme (GBM). With this approval, Monteris will initiate the prospective, open-label Feasibility Study on Laser Interstitial Thermal Ablation for the Treatment of Newly Diagnosed GBM (FLAG) trial at five sites in the United States.

The NeuroBlate system, a type of magnetic resonance imaging–guided laser interstitial thermal therapy, is used by surgeons to destroy and coagulate soft-tissue lesions in the brain. Monteris previously conducted an IDE-approved study to evaluate the system in patients with recurrent GBM and recently announced an additional IDE approval to study the system in patients with medically refractory epilepsy.

Source: Monteris Medical, September 8, 2016

Exablate Neuro System For Essential Tremor

The New England Journal of Medicine has published the results from a pivotal study of the Exablate Neuro system (InSightec) in the noninvasive treatment of patients with essential tremor. The study met its primary endpoint, with patients in the Exablate Neuro cohort demonstrating a clinically significant improvement (47%) in composite tremor score at three months compared with no change in the sham-treatment cohort.

The Exablate Neuro system uses high-intensity focused ultrasound waves to ablate targeted tissue through an intact skull with no incisions. During planning and treatment, the patient is fully conscious, lying on the treatment bed in a magnetic resonance imaging scanner.

Source: InSightec, August 25, 2016

Ready-to-Use Rescue Pen For Diabetes Patients

Encouraging results have been reported from a phase 2 trial of a single-dose version of dasiglucagon (Zealand Pharma) as rescue treatment for severe hypoglycemia in insulin-dependent patients with type-1 diabetes. Dasiglucagon, formerly known as ZP4207, is a glucagon peptide analogue with physical and chemical stability in liquid solution. Current hypoglycemia rescue treatments are based on native glucagon and are available only as a lyophilized powder, which requires reconstitution with sterile water before use.

The study results showed that all patients treated with one of the three highest doses of dasiglucagon or with an approved glucagon product achieved a blood glucose concentration greater than 70 mg/dL within 30 minutes of dosing. In the same dose groups, the time to clinically relevant plasma glucose increases greater than 20 mg/dL was similar for dasiglucagon and approved glucagon, with a median time of nine to 10 minutes.

Source: Zealand Pharma, August 11, 2016