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Drug and Device News March 2018
NEW DRUG APPROVALS
Lutathera for GEP-NETs
The FDA has approved lutetium Lu 177 dotatate (Lutathera, Advanced Accelerator Applications S.A.) to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults, including foregut, midgut, and hindgut neuroendocrine tumors.
Lutathera, which received an orphan drug designation, is the first FDA-approved peptide receptor radionuclide therapy, a targeted treatment comprising a targeting molecule that carries a radioactive component. The company radio-labeled the same targeting molecule with gallium 68 for diagnostic purposes.
The approval is based mainly on the randomized, pivotal, phase 3 NETTER-1 trial, which compared Lutathera plus best standard of care (octreotide LAR 30 mg every four weeks) with 60 mg of octreotide LAR alone (also every four weeks) in patients with inoperable midgut NETs progressing under standard-dose octreotide LAR treatment and overexpressing somatostatin receptors. Patients in the Lutathera arm had a 79% reduction in risk of disease progression or death compared with patients in the 60-mg octreotide LAR arm. A preplanned interim overall survival analysis showed that treatment with Lutathera versus 60-mg octreotide LAR led to a 48% reduction in the estimated risk of death.
The most common grade 3–4 adverse reactions occurring with greater frequency among Lutathera patients were lymphopenia, increased gamma-glutamyl transferase, vomiting, nausea, elevated aspartate aminotransferase, increased alanine aminotransferase, hyperglycemia, and hypokalemia.
Source: Advanced Accelerator Applications S.A., January 26, 2018
Mikart, Inc., has received approval to market butalbital/acetaminophen capsules, 50 mg/300 mg, the first generic version of Phrenilin Forte capsules, 50 mg/650 mg. The drug is indicated for the relief of the symptom complex of tension (muscle contraction) headache.
Source: FDA, December 27, 2017
The FDA has approved marketing of efavirenz capsules USP, 50 mg, 100 mg, and 200 mg, by Aurobindo Pharma Ltd. This is the first generic formulation of Sustiva (Bristol-Myers Squibb), which is indicated for the treatment of human immunodeficiency virus-1 infection.
Source: FDA, December 15, 2017
Triamcinolone Acetonide Suspension
Amneal Pharmaceuticals has received approval to market the first generic triamcinolone acetonide injectable suspension USP in 40 mg/mL vials, 200 mg/5 mL (40 mg/mL) multidose vials, and 400 mg/10 mL (40 mg/mL) multidose vials. The injectable corticosteroid was branded as Kenalog (Apothecon) and is indicated as adjunctive therapy for short-term administration for acute episodes or exacerbations of rheumatoid arthritis.
Source: FDA, December 13, 2017
Trulance for IBS With Constipation
The FDA has approved plecanatide (Trulance, Synergy Pharmaceuticals, Inc.) for once-daily treatment of irritable bowel syndrome with constipation (IBS-C) in adults. Plecanatide was previously approved to treat adults with chronic idiopathic constipation.
Except for a single amino acid substitution for greater binding affinity, plecanatide is structurally identical to human uroguanylin and is thought to replicate the pH-sensitive activity of uroguanylin. The 3-mg tablet can be taken with or without food at any time of day.
The phase 3 IBS-C program for plecanatide included two randomized, 12-week, double-blind, placebo-controlled trials. More than 2,100 patients received once-daily plecanatide (3 mg or 6 mg) or placebo. Patients met Rome III IBS-C criteria for abdominal pain and stool changes. The primary endpoint for both trials was the percentage of patients who, during the 12-week treatment period, had both a 30% or more reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement from baseline, in the same week, for at least 50% of the 12 treatment weeks.
In both trials, plecanatide met the primary endpoint versus placebo (Study 1, 30.2% versus 17.8%; Study 2, 21.5% versus 14.2%). The most common adverse event was diarrhea, but discontinuation rates were low.
Plecanatide is contraindicated in patients younger than 6 years of age and should be avoided in patients 6 to 18 years of age.
Source: Synergy Pharmaceuticals, Inc., January 25, 2018
Gilotrif for More Lung Cancer
The FDA has expanded the indication for afatinib (Gilotrif, Boehringer Ingelheim) to include first-line treatment of metastatic non–small-cell lung cancer (NSCLC) with three additional nonresistant epidermal growth factor receptor (EGFR) mutations: L861Q, G719X, and S768I.
Afatinib, an oral, once-daily tablet, was previously approved in the U.S. for the first-line treatment of patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, afatinib is approved in the U.S. for patients with squamous-cell lung carcinoma whose disease has progressed after treatment with platinum-based chemotherapy.
The new approval is based on a pooled analysis of three studies from the LUX-Lung trial program that examined afatinib in NSCLC patients whose tumors have EGFR mutations, including L861Q, G719X, or S768I. The analysis showed that afatinib was active in these EGFR mutations based on objective response rate, duration of response, disease control, progression-free survival, and overall survival.
To see if a patient is eligible for afatinib, physicians must conduct a test for genetic mutations to determine the type of EGFR mutation present.
Source: Boehringer Ingelheim, January 16, 2018
Fluarix for Children 6 Months Old
The indicated minimum age for use of Fluarix Quadrivalent (influenza vaccine, GlaxoSmithKline) has been lowered from 3 years to 6 months. The vaccine is approved for active immunization against influenza A subtype viruses and type B viruses. Providers can use the same dose of Fluarix Quadrivalent (15 mcg of hemagglutinin per virus strain in 0.5 mL) to cover all eligible patients.
The supplemental biologics license application was based on a phase 3 pivotal study of the vaccine’s efficacy in children 6 months through 35 months of age and on two supportive studies.
Source: GlaxoSmithKline, January 11, 2018
Lynparza for Breast Cancer
The FDA has approved olaparib (Lynparza, AstraZeneca/Merck) for use in patients with deleterious or suspected deleterious germline BRCA-mutated human epidermal growth factor receptor-2–negative metastatic breast cancer who have been treated previously with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Patients are selected for therapy based on an FDA-approved diagnostic test.
The approval was based on the randomized, open-label, phase 3 OlympiAD trial, which investigated olaparib versus physician’s choice of chemotherapy (capecitabine, eribulin [Halaven, Eisai, Inc.], or vinorelbine). Olaparib significantly prolonged progression-free survival to 7.0 months compared with 4.2 months for chemotherapy, reducing the risk of disease progression or death by 42%. Patients with measurable disease taking olaparib experienced an objective response rate of 52%, double the 23% response rate for those in the chemotherapy arm.
The most common adverse reactions with olaparib in the OlympiAD trial were nausea, anemia, fatigue, vomiting, neutropenia, respiratory tract infection, leukopenia, diarrhea, and headache.
Olaparib is the first poly (ADP-ribose) polymerase inhibitor approved beyond ovarian cancer.
Source: AstraZeneca/Merck, January 12, 2018
Xgeva to Prevent Skeletal Events in Multiple Myeloma
The FDA has approved denosumab (Xgeva, Amgen) for the prevention of skeletal-related events in multiple myeloma patients with bone metastases. Xgeva was previously approved to prevent skeletal events in patients with bone metastases from solid tumors.
Denosumab is a fully human monoclonal antibody that binds to and neutralizes RANK ligand—a protein essential for the formation, function, and survival of osteoclasts—thereby inhibiting osteoclast-mediated bone destruction.
The international, phase 3, randomized, double-blind, multicenter ‘482 study compared denosumab with zoledronic acid for the prevention of skeletal-related events in 1,718 patients (859 in each arm) with newly diagnosed multiple myeloma and bone disease. The study demonstrated denosumab’s noninferiority to zoledronic acid in delaying the time to first on-study skeletal-related event (pathological fracture, radiation to bone, surgery to bone, or spinal cord compression).
Overall survival was comparable between the two drugs; progression-free survival favored denosumab by 10.7 months. Adverse events in patients treated with denosumab, such as diarrhea and nausea, were generally consistent with denosumab’s known safety profile.
Source: Amgen, January 5, 2018
FDA REVIEW ACTIVITIES
Breakthrough Therapy Status
Lenvima and Keytruda For Kidney Cancer
Eisai and Merck have received a breakthrough therapy designation for Eisai’s multiple receptor tyrosine kinase inhibitor lenvatinib (Lenvima) in combination with Merck’s anti-programmed death-1 therapy pembrolizumab (Keytruda) for the potential treatment of patients with advanced and/or metastatic renal cell carcinoma (RCC).
The designation was based on results of the RCC cohort in Study 111, a multicenter, open-label phase 1b/2 clinical study being carried out in the U.S. and European Union in patients with select solid tumors. The primary objective of the phase 1b part was to determine the maximum tolerated dose. The phase 2 part, now under way, involves patients with select solid tumors and up to two prior lines of systemic therapy. The primary endpoint is objective response rate at 24 weeks after treatment.
Source: Eisai/Merck, January 9, 2018
Promacta for Severe Aplastic Anemia
The FDA has granted a breakthrough therapy designation to eltrombopag (Promacta, Novartis) as first-line therapy in combination with standard immunosuppressive therapy for severe aplastic anemia (SAA). Eltrombopag is already approved as a second-line SAA therapy in the refractory setting. It is also approved for patients with chronic immune thrombocytopenia refractory to other treatments.
SAA is a rare blood disorder in which bone marrow fails to produce enough red blood cells, white blood cells, and platelets. Up to one-third of patients do not respond to current therapies or they relapse.
Data supporting the designation showed that more than half of treatment-naïve SAA patients achieved a complete response with eltrombopag along with standard immunosuppressive therapy, for an overall response rate of 85%.
Source: Novartis, January 4, 2018
Kisqali for Advanced Breast Cancer
Novartis has received a breakthrough designation for ribociclib (Kisqali) in combination with oral endocrine therapy for premenopausal or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2–negative advanced or metastatic breast cancer.
The designation is based on positive results of the phase 3 MONALEESA-7 trial, which found ribociclib in combination with tamoxifen or an aromatase inhibitor significantly prolonged progression-free survival compared with endocrine therapy alone (median 23.8 months versus 13 months).
This is the second breakthrough therapy designation granted to ribociclib. The first was granted in August 2016 based on results of the phase 3 MONALEESA-2 trial.
Source: Novartis, January 3, 2018
Priority Review Designations
Apalutamide for Prostate Cancer
The FDA has granted a priority review designation for apalutamide (Janssen Biotech, Inc.), an investigational, next-generation oral androgen receptor inhibitor for nonmetastatic castration-resistant prostate cancer (CRPC).
Prostate cancer patients eventually become resistant to androgen deprivation therapy, developing CRPC. Patients with nonmetastatic CRPC are at high risk for developing metastatic disease. Apalutamide inhibits the action of androgen in prostate cancer cells. It prevents binding of androgen to the androgen receptor and translocation of the androgen receptor to the nucleus of the cancer cell.
The new drug application was based on phase 3 data from the SPARTAN clinical trial, which compared apalutamide with placebo. The FDA has assigned a Prescription Drug User Fee Act target date in April 2018.
Source: Janssen Biotech, Inc., December 21, 2017
Tafinlar, Mekinist for Melanoma Positive for BRAF V600 Mutation
The FDA has granted Novartis priority review for dabrafenib (Tafinlar) in combination with trametinib (Mekinist) for the adjuvant treatment of patients with stage III melanoma with BRAF V600E or BRAF V600K mutations. In October, the FDA also granted breakthrough therapy designation to this combination for the adjuvant treatment of patients with stage III melanoma with a BRAF V600 mutation following complete resection.
The priority review designation is based on phase 3 findings showing a 53% reduction in risk of recurrence or death with dabrafenib plus trametinib compared with placebo. The study also showed improvements in key secondary endpoints, including overall survival, distant metastasis-free survival, and freedom from relapse.
Dabrafenib plus trametinib is approved in the U.S. for patients with unresectable or metastatic melanoma with a BRAF V600E/K mutation as detected by an FDA-approved test and non–small-cell lung cancer with a BRAF V600E mutation. The two drugs target different kinases—BRAF and MEK1/2, respectively—in the RAS/RAF/MEK/ERK pathway. The combination has been shown to slow tumor growth more than either drug alone.
Source: Novartis, December 22, 2017
Inotersen for Hereditary ATTR Amyloidosis
The FDA has accepted for priority review a new drug application for inotersen (Ionis), an investigational drug to treat hereditary transthyretin amyloidosis (hATTR). The FDA has set a Prescription Drug User Fee Act date of July 6, 2018.
ATTR is a severe, progressive, and fatal disease in which both the mutant and wild-type TTR build up as fibrils in tissues. As the TTR protein fibrils enlarge, more tissue is damaged and the disease worsens.
Inotersen is an antisense drug designed to reduce the production of transthyretin. In a phase 3 study (NEURO-TTR) of patients with polyneuropathy due to hATTR, inotersen demonstrated a benefit compared with placebo at both eight and 15 months of treatment. Consistent and significant benefit was observed independent of disease stage, types of mutation, previous treatment with TTR protein stabilizers, or presence of cardiomyopathy at the beginning of the study. The overall mortality rate in the NEURO-TTR study was 2.9%, lower than rates reported in other studies with hATTR patients.
Source: Ionis Pharmaceuticals, Inc., January 8, 2018
Kymriah for Relapsed/Refractory Diffuse Large B-Cell Lymphoma
The FDA has granted priority review status to tisagenlecleucel suspension for intravenous infusion (Kymriah, Novartis) as a treatment for patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who are ineligible for or relapse after autologous stem cell transplant.
In August 2017, tisagenlecleucel became the first chimeric antigen receptor T-cell (CAR-T) therapy to receive FDA approval for the treatment of patients up to 25 years of age with B-cell precursor acute lympho-blastic leukemia (ALL) that is refractory or in second or later relapse. Tisagenlecleucel is a one-time immunocellular therapy that uses a patient’s own T cells to fight cancer. T cells drawn from the patient’s blood are reprogrammed in the laboratory to create T cells genetically coded to recognize and fight the patient’s cancer cells and other B cells expressing a particular antigen.
The new review is based on data from a global clinical trial program of tisagenlecleucel in children and young adults with r/r B-cell ALL and adults with r/r DLBCL, and results from two pivotal, phase 2, multicenter, global registration studies (JULIET and ELIANA).
Source: Novartis, January 17, 2018
Adcetris for Advanced Hodgkin’s
The FDA has accepted for filing a supplemental biologics license application for brentuximab vedotin (Adcetris, Seattle Genetics, Inc.) in combination with chemotherapy for the first-line treatment of patients with advanced classical Hodgkin’s lymphoma (HL). The FDA granted priority review and set a Prescription Drug User Fee Act target action date of May 1, 2018.
Adcetris is an antibody–drug conjugate directed to CD30, a defining marker of classical HL. The application is based on positive results from the phase 3 clinical trial ECHELON-1 in previously untreated advanced classical HL patients. The study found combining Adcetris and AVD (adriamycin, vinblastine, dacarbazine) resulted in a statistically significant improvement in modified progression-free survival versus ABVD (AVD plus bleomycin), with a 23% reduction in the risk of progression, death, or need for additional anticancer therapy.
Source: Seattle Genetics, Inc., January 2, 2018
Tafenoquine to Prevent Malaria
The FDA has granted a fast-track designation to 60 Degrees Pharmaceuticals to investigate tafenoquine for prevention of malaria in adults. The company has a cooperative research and development agreement with the U.S. Army Medical Materiel Development Activity to develop tafenoquine as a weekly prophylactic drug. Submission of the new drug application culminates more than 30 years of research and development with the Army.
In five clinical trials, tafenoquine appeared to be safe and well tolerated when the anticipated clinical regimen was administered. The majority of adverse events were mild or considered unrelated to the study drug.
Source: 60 Degrees Pharmaceuticals, January 4, 2018
Ulimorelin for Enteral Feeding Intolerance
Lyric Pharmaceuticals has received a fast-track designation for ulimorelin (LP101) for the treatment of enteral feeding intolerance (EFI) in critically ill patients.
In EFI, impaired gastric emptying prevents delivery of adequate enteral nutrition. EFI is associated with significant morbidity and mortality. No drug is approved for EFI. Ulimorelin is a macro-cyclic agonist of the hormone ghrelin. Ghrelin agonists may offer both gastrointestinal pro-motility and pro-metabolic effects, and may mitigate muscle loss associated with EFI.
Lyric has completed two phase 1 trials of LP101 demonstrating gastrointestinal prokinetic activity. PROMOTE, a phase 2, randomized, multinational, multicenter trial, is under way, with data expected in mid-2018.
Source: Lyric Pharmaceuticals, January 17, 2018
SOBI003 for MPS IIIA
The FDA has accepted the investigational new drug application for SOBI003 (Swedish Orphan Biovitrum AB) and given it fast-track status. SOBI003 is a chemically modified human recombinant sulfamidase for the treatment of muco-polysaccharidosis type IIIA (MPS IIIA), a rare metabolic disorder also known as Sanfilippo syndrome type A.
MPS IIIA is an inherited, progressive, life-threatening disorder in which the body is unable to break down heparan sulfate, resulting in its accumulation in lysosomes. MPS IIIA mainly affects the central nervous system, where it causes severe progressive degeneration. There is no treatment for MPS IIIA.
SOBI003 is an enzyme replacement therapy to reduce heparan sulfate storage materials in affected cells. SOBI003 is taken up by cells and transported into the lysosomal compartment, where heparan sulfate is degraded. Modification of the molecule results in an extended half-life.
A clinical study with SOBI003 is expected to start during 2018.
Source: Swedish Orphan Biovitrum AB, January 23, 2018
RT-100 AC6 Gene Transfer For Heart Failure
Renova Therapeutics has been granted a fast-track designation for RT-100 AC6 gene transfer (Ad5.hAC6) for the treatment of heart failure (HF) with reduced ejection fraction.
RT-100 AC6 gene transfer involves infusing an inactivated adenovirus vector encoding human adenylyl cyclase type 6 (Ad5.hAC6) into the arteries that feed the heart during cardiac catheterization. AC6 is a protein found in heart muscle cells that regulates heart function and appears to be downregulated in HF patients.
Results of a phase 2 clinical trial indicate that, through a one-time administration, RT-100 safely increased heart function beyond optimal HF therapy. The treatment also lowered the HF hospitalization rate at 12 months. A phase 3 trial, FLOURISH, is planned for 2018.
Source: Renova Therapeutics, December 14, 2017
VAL-083 for Recurrent Glioblastoma
The FDA has granted fast-track designation for VAL-083 (DelMar Pharmaceuticals) in recurrent glioblastoma (rGBM).
VAL-083 (dianhydrogalactitol) is a first-in-class DNA-targeting agent that has demonstrated clinical activity against a range of cancers in clinical trials sponsored by the National Cancer Institute. According to study findings, VAL-083’s antitumor activity is unaffected by common mechanisms of chemoresistance in vitro.
DelMar is conducting a phase 2 study in bevacizumab-naïve MGMT-unmethylated GBM patients and a phase 3 study of patients whose disease has progressed following prior treatment with temozolomide and bevacizumab (the STAR-3 trial). Outside of rGBM, DelMar has initiated a phase 2 clinical trial of VAL-083 in newly diagnosed MGMT-unmethylated GBM and plans a phase 1/2 trial of VAL-083 in patients with recurrent platinum-resistant ovarian cancer.
Source: DelMar Pharmaceuticals, Inc., December 26, 2017
CTP-543 for Alopecia Areata
The FDA has given Concert Pharmaceuticals a fast-track designation for CTP-543, a novel oral Janus kinase (JAK) inhibitor for the treatment of moderate-to-severe alopecia areata.
Alopecia areata, an autoimmune disease, results in partial or complete loss of hair on the scalp and body. There are no FDA-approved drugs for its treatment.
CTP-543 was discovered by applying Concert’s deuterium chemistry technology to modify ruxolitinib (Jakafi, Incyte Corp.), which selectively inhibits JAK1 and JAK2 and is available in the U.S. for the treatment of certain blood disorders. Ruxolitinib has been used to treat alopecia areata in academic settings and has been reported to promote hair growth in individuals with moderate-to-severe disease. Concert is conducting a phase 2a trial to evaluate CTP-543’s safety and efficacy in adults with moderate-to-severe alopecia areata.
Source: Concert Pharmaceuticals, January 12, 2018
CNTX-4975 for Knee Osteoarthritis Pain
Centrexion Therapeutics has been granted a fast-track designation for CNTX-4975, a therapy for pain associated with knee osteoarthritis. In the phase 2b TRIUMPH trial, treatment with CNTX-4975 resulted in one of the largest reductions of pain associated with knee osteoarthritis reported in any placebo-controlled clinical trial.
CNTX-4975 is a highly potent, synthetic form of transcapsaicin, a medicine traditionally derived from the chili plant. It is injected directly into the site of pain to provide rapid onset and pain relief without affecting touch sensibility or position sense.
CNTX-4975 targets the capsaicin receptor (TRPV1) to selectively and rapidly inactivate local pain fibers transmitting signals to the brain. With a short half-life, CNTX-4975 is cleared from the body within 24 hours. This approach is designed to provide pain relief that can last for months until the ends of the local pain fibers regenerate, without the risks associated with nonsteroidal anti-inflammatory drugs, injected corticosteroids, or opioid treatments.
Source: Centrexion Therapeutics Corporation, January 16, 2018
VNRX-5133 for Gram-Negative Infections
The FDA has granted fast-track status to VNRX-5133 (VenatoRx Pharmaceuticals), an injectable broad-spectrum beta-lactamase inhibitor combined with a marketed beta-lactam antibiotic. Designations were granted for complicated urinary tract infections and complicated intra-abdominal infections.
VNRX-5133 is a novel beta-lactamase inhibitor with potent and selective direct inhibitory activity against both serine-and metallo-beta-lactamases. Combined with a marketed beta-lactam antibiotic, VNRX-5133 has the potential to address the serious unmet medical need for a safe and effective treatment of infections caused by multidrug-resistant gram-negative bacteria, particularly carbapenem-resistant Enterobacteriaceae and multidrug-resistant Pseudomonas aeruginosa.
Source: VenatoRx Pharmaceuticals, January 3, 2018
Orphan Drug Desigations
EC-18 for Acute Radiation Syndrome
The FDA has granted an orphan drug designation to EC-18 (Enzychem Life-sciences Corp.) for the treatment of acute radiation syndrome (ARS).
Caused by a critical exposure to radiation, ARS includes neutropenia, nervous system damage, and pneumonia, with a high fatality rate. The U.S. government encourages development of new ARS drugs in response to an increasing threat of bioterrorism. EC-18 could also have a role in treating immune and inflammatory-related diseases, including psoriasis, rheumatoid arthritis, asthma, atopic dermatitis, and sepsis.
EC-18 is a small-molecule compound designed for oral administration. Phase 2 clinical trials on indications for chemotherapy-induced neutropenia and chemo-radiotherapy-induced oral mucositis are under way.
Source: Enzychem Lifesciences Corp., January 19, 2018
BB-301 for Oculopharyngeal MD
Benitec Biopharma Ltd. has been granted an orphan drug designation for BB-301 for the treatment of oculopharyngeal muscular dystrophy (OPMD).
BB-301 is a single-vector (gene therapy construct) system that uses DNA-directed RNA interference to silence expression of the mutant gene associated with OPMD, while simultaneously returning a copy of the normal gene to restore its function. Benitec intends to file an investigational new drug application in late 2018.
Source: Benitec Biopharma Ltd., January 16, 2018
Complete Response Letters
Linhaliq for Lung Infections
The FDA has rejected the new drug application for Linhaliq (Aradigm Corp.) as a treatment for patients with non-cystic fibrosis bronchiectasis (NCFBE) who have chronic lung infections with Pseudomonas aeruginosa.
In a complete response letter, the FDA requested third-party verification of existing phase 3 data, an additional phase 3 trial, another human factors study, and additional product quality information. Aradigm will meet with the FDA to discuss the requests and expects to move forward with the application.
The Linhaliq application was based on data from two phase 3 studies (ORBIT-3 and -4) and a phase 2b study (ORBIT-2).
Source: Aradigm, January 29, 2018
CAM2038 for Opioid Use Disorder
The FDA has sent a complete response letter to Braeburn Pharmaceuticals requesting additional information on its new drug application for CAM2038, an investigational buprenorphine weekly and monthly depot injection for the treatment of adults with opioid use disorder (OUD). There is no need for additional clinical studies, Braeburn said; the company did not specify what information the FDA is seeking.
CAM2038 was previously granted fast-track and priority review designations by the FDA. If approved, it would be the first injectable for OUD that can be administered by health care professionals from day 1 of OUD treatment.
Source: Braeburn, January 21, 2018
DRUG SAFETY ISSUES
Anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions—some requiring hospitalization—have been reported during or soon after infusion of rolapitant injectable emulsion (Varubi, Tesaro, Inc.), the FDA says. Most reactions have occurred within the first few minutes of administration. Symptoms can include wheezing or difficulty breathing; swelling of the face or throat; hives or flushing; itching; abdominal cramping, abdominal pain, or vomiting; back pain or chest pain; hypotension; or shock.
Rolapitant injectable emulsion is approved to prevent delayed-phase chemotherapy-induced nausea and vomiting. It is approved in adults in combination with antiemetic agents that prevent nausea and vomiting associated with initial and repeat courses of emetogenic and highly emetogenic cancer chemotherapy.
The agency warned health care professionals to be vigilant for signs of hypersensitivity or anaphylaxis in all patients receiving rolapitant injectable emulsion, both during and following its administration. Health care professionals should determine if the patient is hypersensitive to any component of the product, including soybean oil. Patients with known allergies to legumes or other related allergens should be monitored closely. Appropriate treatment should be available for immediate use in the event of an anaphylactic reaction.
Source: FDA, January 16, 2018
Cough and Cold Products
The FDA is requiring safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone to limit their use to adults 18 years of age and older after concluding that the risks of these medicines outweigh their benefits in children younger than 18. The agency is also requiring the addition of safety information about the risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing to the boxed warning of the products’ labels.
The change was based on an extensive review and the advice of a panel of outside experts. Health care professionals should reassure parents that cough due to a cold or upper respiratory infection is self-limited and generally does not need treatment. For children in whom cough treatment is necessary, alternative medicines are available.
Source: FDA, January 11, 2018
Flawless Beauty Recall
Under court order, Flawless Beauty, LLC, is recalling all lots of 19 products sold individually or as part of multiunit kits that the FDA alleges to be misbranded or unapproved drugs.
The products were sold and distributed over the Internet: Relumins Advanced Glutathione kits with 900-mg vials; Relumins Advanced Glutathione kits with 1,500-mg vials; Relumins Advanced Glutathione kits with 3,000-mg vials; Relumins Vitamin C Solvent ampules; Tatiomax Gluatathione Whitening kits with 1,400-mg vials; Saluta Glutathione Whitening kits with 600-mg vials; Saluta Glutathione Whitening kits with 1,200-mg vials; Saluta Glutathione Whitening kits with 1,800-mg vials; Laroscorbine Platinum Vitamin C with Collagen 1,100 mg; Tationil Glutathione Whitening 10-vial kits; Tationil Glutathione Whitening (five sets of 10-vial kits); Laennec Human Placenta Whitening kits 2-mL vials; Reiki Glutathione Whitening kits; TAD Glutathione Whitening kits with 600-mg vials; TP Drug Laboratories Vitamin C ampules; Sterile water ampules; and Ling Zhi capsules.
Source: FDA, January 19, 2018
Centric Foot and Ankle System
The Centric Medical Foot and Ankle Plating System and Centric Medical Cannulated Screw Internal Fixation System have secured FDA 510(k) clearance.
The plating system includes a variety of plates and screws intended to stabilize and fixate bone for a myriad of procedures. The low-profile plates and self-drilling and self-tapping screws were designed to minimize soft tissue disruption and irritation. They are offered in many sizes and shapes that include plates specifically designed for metatarsal phalangeal fusions, lapidus fusions, midfoot fusions, and calcaneal slide osteotomies.
The cannulated screws are made of titanium alloy in a variety of diameters and lengths. The new options, specifically indicated for the forefoot, complement previously cleared products indicated for the midfoot and hindfoot.
Source: Centric Medical, January 16 and 23, 2018
GammaCore for Migraine
The FDA has cleared expanded labeling for gammaCore (electroCore, LLC) that includes acute treatment of pain associated with migraine in adults. Gamma-Core is a noninvasive neuromodulation treatment delivered by a hand-held unit that stimulates the vagus nerve through the skin. GammaCore received initial FDA clearance for the acute treatment of pain associated with episodic cluster headache in adults in April 2017.
The new clearance was supported mainly by results of the multicenter, randomized, double-blind, sham-controlled PRESTO trial, which demonstrated that for the acute treatment of pain associated with migraine, gammaCore enabled patients to reach pain freedom more frequently by 30, 60, and 120 minutes compared with sham treatment.
Source: electroCore, LLC, January 29, 2018
TechLab Campylobacter Tests
The FDA has cleared Campylobacter Quik Chek and Campylobacter Chek (TechLab, Inc.), tests intended to aid diagnosis of campylobacteriosis.
Campylobacter Quik Chek is a rapid diagnostic test that detects Campylobacter jejuni and C. coli in less than 30 minutes. Campylobacter Chek is a 96-well plate format for laboratories testing large numbers of specimens and can be used with or without automation. The two tests’ accuracy surpasses culture with the highest positive predictive values among available Campylobacter immunoassays, the company says.
Source: TechLab, Inc., January 23, 2018
Flex Robotic System
The FDA has approved marketing of the Flex Robotic System (Medrobotics Corp.) for robot-assisted visualization in general surgical, gynecological, and thoracic procedures. With this new indication, the use of Medrobotics’ flexible robotic technology extends beyond natural orifices. The Flex system provides access to hard-to-reach anatomy in otolaryngology and colorectal procedures; the company is pursuing expansion of applications to other areas.
Source: Medrobotics Corp., January 22, 2018
The Telemark 0.014-inch coronary and peripheral support microcatheter (Surmodics, Inc.) has received FDA 510(k) clearance. The microcatheter offers superior crossability for complex coronary and peripheral lesions. The microcatheter combines Surmodics’ Xtreme composite shaft technology with a high-performance Pristyne hydrophilic to provide exceptional deliverability, kink resistance, and lesion crossing.
Source: Surmodics, January 22, 2018
DEVICE SAFETY ISSUES
Enteral Access Systems
The FDA received 51 reports from January 2012 to July 2017 about pneumothorax events related to the Cortrak 2 Enteral Access System (Corpak Medsystems) during feeding tube placements. The reports included 11 deaths, but their relationship to the pulmonary events “cannot be concluded definitively in all cases,” the FDA said. Most pulmonary events required urgent intervention, including needle decompression or chest tube placement, and several were associated with cardiopulmonary arrest.
An enteral access system (EAS) is designed to aid in the placement of nasoenteric feeding tubes by transmitting real-time positional information to an external visible screen or console. The Cortrak 2 EAS uses electromagnetic sensors in a stylet to provide a visual representation of the tip of the tube relative to an external receiving unit placed over the patient’s xiphoid process.
Pneumothorax is a known rare complication of blind insertion of feeding tubes, typically less than 0.5%. The FDA cannot determine how the rate of EAS complications compares to that estimated for blind insertion.
During that same 5.5-year period, the FDA received one report of a nonfatal pneumothorax event associated with a different EAS technology, Kangaroo Feeding Tube with IRIS Technology. That event occurred following blind placement of the tube without use of the video console.
The FDA recommends EAS devices be used only by appropriately trained and credentialed clinical staff. The devices should not be used in patients with contraindications for nasoenteric feeding tubes. If resistance is met during placement or the patient demonstrates signs of respiratory distress, the tube should be withdrawn and the patient reassessed.
For the Cortrak device, the FDA also recommends that users ensure that the receiver is properly aligned and immobile; observe the real-time tracing to ensure the proper path of the tube; and use the device with caution in proximity to other electrical equipment, as readings may be impacted.
Source: FDA, January 12, 2018
Zoll LifeVest 4000
Zoll is recalling its LifeVest 4000 because the wearable defibrillator may fail to deliver a life-saving shock to patients who don’t heed a device-generated message telling them to call for service. The FDA says one such patient died.
About 25,000 of the devices have been distributed in the U.S. The FDA is working with Zoll to identify a solution.
The Zoll LifeVest 4000 is a wearable defibrillator used to treat life-threatening arrhythmias in people at risk for sudden cardiac arrest who are not candidates for, or refuse, an implantable defibrillator. It continuously monitors the patient’s heart and, if a life-threatening heart rhythm is detected, delivers a shock to restore normal heart rhythm.
However, a fault in the LifeVest 4000 can prevent the device from charging its high-energy capacitors. The device screen will display, “Call for service: Device has a problem that may require service. Call ZOLL for service, Message Code 102.” The device may fail to function if the device is not replaced soon. “Message Code 102” does not explicitly tell the patient that the device cannot be used and that the patient should call Zoll immediately.
The FDA advises providers to teach patients to identify and respond to the “Message Code 102” alert. Otherwise, patients should continue to use the Life-Vest 4000 as prescribed.
Source: FDA, January 17, 2018
Vyaire Humidification Chamber
Vyaire Medical is recalling 16,670 AirLife Humidification Chamber and Heated Breathing Circuit Kits because a manufacturing error may cause parts of the chamber to split into layers, allowing water to overflow the chamber and back up into the patient breathing circuit. This could cause an excessive amount of water to enter the airway or lungs of a ventilated patient and lead to serious consequences, including injury or death.
The kits are used with invasive and noninvasive ventilation systems to provide constant humidified breathing gasses for adults and children. This class 1 recall covers lots AH290, AH132, AH265, AH202, and AH280, distributed from July 3, 2017, to November 10, 2017.
Source: FDA, January 31, 2018