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Drug and Device News July 2018
NEW DRUG APPROVALS
Andexxa for Reversal Of Anticoagulation
The FDA has approved Andexxa (coagulation factor Xa [recombinant], inactivated-zhzo), the first and only antidote indicated for patients treated with rivaroxaban (Xarelto, Janssen Pharma ceuticals) and apixaban (Eliquis, Bristol-Myers Squibb), when reversal of anti coagulation is needed due to life-threatening or uncontrolled bleeding. It was approved under the FDA’s accelerated approval pathway based on the change from baseline in anti-factor Xa activity in healthy volunteers. Continued approval for this indication may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients.
The use of factor Xa inhibitors is rapidly growing because of their efficacy and safety profile compared to enoxaparin and warfarin in preventing and treating thromboembolic conditions such as stroke, pulmonary embolism, and venous thromboembolism.
The approval of Andexxa is supported by data from two phase 3 studies (ANNEXA-R and ANNEXA-A), which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers. As described in the label, results demonstrated that Andexxa rapidly and significantly reversed anti-factor Xa activity (the anticoagulant mechanism of these medicines). The median decrease in anti-factor Xa activity from baseline was 97% for rivaroxaban and 92% for apixaban.
The labeling for Andexxa contains a boxed warning for thromboembolic risk, ischemic risk, cardiac arrest, and sudden death.
Source: Portola Pharmaceuticals, May 3, 2018
Imvexxy for Dyspareunia
TherapeuticsMD’s Imvexxy (estradiol vaginal inserts) has received FDA approval for the treatment of moderate-to-severe dyspareunia (vaginal pain associated with sexual activity), a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Imvexxy is the only product in its therapeutic class to offer a 4-mcg and 10-mcg dose, the 4-mcg representing the lowest approved dose of vaginal estradiol available.
Imvexxy’s mechanism of action is the re-estrogenization of the tissue in and around the vagina. Its formulation ensures that it dissolves completely without mess, so patients can use it any time of day by placing the softgel capsule in the lower part of the vagina to treat the vulva and vagina. The drug is administered daily for two weeks followed by only twice-a-week dosing.
The FDA approval of Imvexxy is based on the results of a phase 3, randomized, double-blind, placebo-controlled study that evaluated the safety and efficacy of Imvexxy (4 mcg and 10 mcg) compared with placebo from baseline to week 12. The study showed that Imvexxy provided relief of moderate-to-severe dyspareunia due to menopause as early as week 2 for both doses. The most common adverse reaction was headache.
The Imvexxy prescribing information contains a boxed warning for endometrial cancer, cardiovascular disorders, breast cancer, and probable dementia.
Source: TherapeuticsMD, May 30, 2018
Yonsa for Metastatic CRPC
The FDA has approved Yonsa (abiraterone acetate, Sun Pharma), a novel formulation in combination with methylprednisolone, for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).
Yonsa is a cytochrome P450 (CYP) 17 inhibitor that uses proprietary technology to create a micronized formulation of abiraterone acetate tablets. The active ingredient is converted in vivo to abiraterone, an androgen biosynthesis inhibitor that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). The CYP17 enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis.
Yonsa contains the same drug as and will be a competitor to Janssen’s Zytiga (abiraterone acetate). Because Yonsa in combination with methylprednisolone has a novel micronized formulation, it was approved as a new drug under the 505(b)(2) regulatory pathway and will be promoted as a branded product in the U.S.
Source: Sun Pharma, May 23, 2018
Lokelma For Hyperkalemia
Sodium zirconium cyclosilicate (Lokelma, AstraZeneca), formerly ZS-9, has received FDA approval for the treatment of adults with hyperkalemia, a serious condition characterized by elevated potassium levels in the blood associated with cardiovascular, renal, and metabolic diseases.
The risk of hyperkalemia increases significantly for patients with chronic kidney disease and for those who take common medications for heart failure, such as renin–angiotensin–aldosterone system (RAAS) inhibitors, which can increase potassium in the blood. To help prevent the recurrence of hyperkalemia, RAAS-inhibitor therapy is often modified or discontinued, which can compromise cardio-renal outcomes and increase the risk of death.
Sodium zirconium cyclosilicate is a highly selective, oral potassium-removing agent. The FDA approval is supported by data from three double-blind, placebo-controlled trials and two open-label trials, which showed that for patients receiving sodium zirconium cyclosilicate, the onset of action was at 1.0 hour and the median time to achieving normal potassium levels in the blood was 2.2 hours, with 92% of patients achieving normal potassium levels within 48 hours from baseline. The treatment effect was maintained for up to 12 months.
Source: AstraZeneca, May 18, 2018
Jynarque to Slow Kidney Function Decline in ADPKD
The FDA has approved tolvaptan (Jynarque, Otsuka Pharmaceutical Co., Ltd.) as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).
ADPKD is a genetic disease with consequences that can lead to dialysis or kidney transplantation. It is a progressively debilitating and often painful disorder in which fluid-filled cysts develop in the kidneys over time. These cysts enlarge the kidneys and impair their ability to function normally, leading to kidney failure in most patients. ADPKD is diagnosed in approximately 140,000 people in the U.S. and impacts families across multiple generations because a parent with ADPKD has a 50% chance of passing the disease on to each of their children.
Tolvaptan, a selective vasopressin V2-receptor antagonist, was shown to slow the rate of decline in renal function in patients at risk of rapidly progressing ADPKD in two trials: TEMPO 3:4 in patients at earlier stages of disease and REPRISE in patients at later stages. The findings from these trials, when taken together, suggest that tolvaptan slows the loss of renal function progressively through the course of the disease.
Tolvaptan will be sold in a 28-day treatment pack at a wholesale acquisition cost of $13,041.10, according to Otsuka.
Source: Otsuka, April 24, 2018
Plenvu Bowel Prep
The FDA has approved Plenvu (polyethylene glycol 3350, sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride, and potassium chloride for oral solution, Salix Pharmaceuticals, Ltd.), a lower-volume (1-L) polyethylene-glycol–based bowel preparation.
According to patients’ experiences and reported barriers to colonoscopy, most patients perceived the bowel preparation to be the most burdensome part of colonoscopy. Complaints regarding bowel preparation typically relate to the large volumes necessary to consume and the unpleasant taste. By reducing the volume of solution patients must consume for effective bowel cleansing to only 1 L of active solution, the manufacturer hopes to improve the patient colonoscopy preparation experience.
The approval was based on multiple phase 3 clinical trials, including the NOCT study, which compares Plenvu with a trisulfate bowel cleansing solution (Suprep [sodium sulfate, potassium sulfate, and magnesium sulfate, Braintree Laboratories, Inc.]) using a two-day split-dosing regimen in adults. Both primary endpoints were met, achieving non-inferior overall bowel cleansing success and “excellent-plus-good” cleansing of the ascending colon. Plenvu is the only FDA-approved bowel cleanser to offer split dosing on the same day as the colonoscopy procedure.
Plenvu was licensed by Salix from Norgine in August 2016 for introduction to the U.S. market and will be available in the U.S in the third quarter of 2018. In Europe, Plenvu is approved and available through Norgine.
Source: Valeant, May 7, 2018
Doptelet for Chronic Liver Disease and Thrombocytopenia
Avatrombopag tablets (Doptelet, AkaRx, Inc.) have received FDA approval to treat thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure. This is the first drug approved by the agency for this use.
The safety and efficacy of avatrombopag was studied in two trials involving 435 patients with chronic liver disease and severe thrombocytopenia who were scheduled to undergo a procedure that would typically require platelet transfusion. The trials investigated two dose levels of avatrombopag administered orally over five days compared with placebo. The trial results showed that for both dose levels of avatrombopag, a higher proportion of patients had increased platelet counts and did not require platelet transfusion or any rescue therapy on the day of the procedure and up to seven days following the procedure compared with those treated with placebo.
The most common side effects reported by clinical trial participants who received avatrombopag were fever, abdominal pain, nausea, headache, fatigue, and edema. People with chronic liver disease and people with certain blood-clotting conditions may have an increased risk of developing blood clots when taking avatrombopag.
Source: FDA, May 21, 2018
Aimovig for Preventive Treatment for Migraine
The FDA has approved erenumabaooe (Aimovig, Amgen, Inc.) for the preventive treatment of migraine in adults. The treatment is given by once-monthly self-injection. Erenumab is the first FDA-approved preventive migraine treatment in a new class of drugs that work by blocking the activity of calcitonin gene-related peptide, a molecule that is involved in migraine attacks.
The effectiveness of erenumab for the preventive treatment of migraine was evaluated in three clinical trials. The first study included 955 participants with a history of episodic migraine and compared erenumab with placebo. Over the course of six months, erenumab-treated patients experienced, on average, one to two fewer monthly migraine days than those on placebo. The second study included 577 patients with a history of episodic migraine and compared erenumab with placebo. Over the course of three months, erenumab-treated patients experienced, on average, one fewer migraine day per month than those on placebo. The third study evaluated 667 patients with a history of chronic migraine and compared erenumab with placebo. In that study, over the course of three months, patients treated with erenumab experienced, on average, 2.5 fewer monthly migraine days than those receiving placebo.
The most common side effects that patients in the clinical trials reported were injection-site reactions and constipation.
Source: FDA, May 17, 2018
Lucemyra for Opioid Withdrawal Symptoms
The first nonopioid drug for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults—lofexidine hydrochloride (Lucemyra, US WorldMeds LLC)—has been approved by the FDA. While lofexidine may lessen the severity of withdrawal symptoms, it may not completely prevent them and is only approved for treatment for up to 14 days. Lofexidine is not a treatment for opioid use disorder (OUD), but it can be used as part of a broader, long-term treatment plan for managing OUD.
Lofexidine is an oral, selective alpha 2-adrenergic receptor agonist that reduces the release of norepinephrine. The actions of norepinephrine in the autonomic nervous system are believed to play a role in many of the symptoms of opioid withdrawal.
The safety and efficacy of lofexidine was supported by two randomized, double-blind, placebo-controlled clinical trials of 866 adults meeting Diagnostic and Statistical Manual of Mental Disorders (IV) criteria for opioid dependence who were physically dependent on opioids and undergoing abrupt opioid discontinuation. Withdrawal symptom severity was significantly lesser for patients treated with lofexidine compared with placebo, and more patients completed the treatment period in the lofexidine group compared with placebo.
The most common side effects from treatment with lofexidine include hypotension, bradycardia, somnolence, sedation, and dizziness. Lofexidine was also associated with a few cases of syncope. Lofexidine affects the heart’s electrical activity, which can increase the risk of abnormal heart rhythms. When lofexidine is stopped, patients can experience a marked increase in blood pressure. The safety and efficacy of lofexidine have not been established in children or adolescents younger than 17 years of age. After a period of not using opioid drugs, patients may be more sensitive to the effects of lower amounts of opioids if relapse does occur, and taking opioids in amounts that were used before withdrawing from opioids can lead to overdose and death.
Fifteen post-marketing studies, including both animal and human studies, are being required by the FDA.
Source: FDA, May 16, 2018
Retacrit for Anemia
The FDA has approved Retacrit (epoetin alfa-epbx, Hospira, Inc.) as the first biosimilar to Epogen (epoetin alfa, Amgen) and Procrit (epoetin alfa, Janssen) for the treatment of anemia caused by chronic kidney disease, chemotherapy, or use of zidovudine in patients with human immuno deficiency virus infection. Retacrit is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during surgery.
The FDA’s approval is based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharma cokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Retacrit is biosimilar to Epogen and Procrit. Retacrit has been approved as a biosimilar, not as an interchangeable product.
The most common side effects of epoetin alfa-treated patients in clinical studies of the reference product were high blood pressure, joint pain, muscle spasm, fever, dizziness, medical device malfunction, blood vessel blockage, respiratory infection, cough, rash, injection-site irritation, nausea, vomiting, muscle pain, inflammation of the mouth and lips, weight decrease, reduction in white blood cells, bone pain, high blood sugar, insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots, itching, and chills.
The prescribing information for Retacrit contains a boxed warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.
Source: FDA, May 15, 2018
Palynziq for Phenylketonuria
Pegvaliase-pqpz (Palynziq, BioMarin Pharmaceutical, Inc.) has received FDA approval for the treatment of adults with a rare and serious genetic disease known as phenylketonuria (PKU). Patients with PKU are born with an inability to break down phenylalanine (Phe), an amino acid present in protein-containing foods and high-intensity sweeteners used in a variety of foods and beverages. Pegvaliase is a novel enzyme therapy for adult PKU patients who have uncontrolled blood Phe concentrations on current treatment.
The safety and efficacy of pegvaliase were studied in two clinical trials in adult patients with PKU with blood phenyl alanine concentrations greater than 600 μmol/L on existing management. Most PKU patients in the pegvaliase trials were on an unrestricted diet prior to and during the trials. The first trial was a randomized, open-label trial in patients treated with increasing doses of pegvaliase administered as a subcutaneous injection up to a target dose of either 20 mg once daily or 40 mg once daily. The second trial was an eight-week, placebo-controlled, randomized withdrawal trial in patients who were previously treated with pegvaliase. Patients treated with pegvaliase achieved statistically significant reductions in blood phenylalanine concentrations from their pretreatment baseline blood Phe concentrations.
The most common adverse events reported in the pegvaliase trials included injection-site reactions, joint pain, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus, nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough, and diarrhea. Hypersensitivity reactions occurred in most patients, likely due to formation of antibodies to the product.
The most serious adverse reaction in the pegvaliase trials was anaphylaxis, which occurred most frequently during upward titration of the dose within the first year of treatment. Because of this serious risk, the labeling for pegvaliase includes a boxed warning, and the product is available only through a restricted program under a risk evaluation and mitigation strategy (REMS) called the Palynziq REMS Program.
Source: FDA, May 24, 2018
Leukine for Acute Radiation Syndrome
Partner Therapeutics, Inc., has received FDA approval for Leukine (sargramostim) for the treatment of adult and pediatric patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome, or H-ARS). Leukine is the first drug for H-ARS to demonstrate an improvement in survival when initiated 48 hours after radiation exposure.
Acute radiation syndrome (ARS) is an acute illness caused by irradiation of the body by a high dose of penetrating radiation. H-ARS occurs when the radiation exposure results in the destruction of the stem cells resident in the bone marrow that generate and maintain the body’s immune system increasing the risk of infection, bleeding, and death. Leukine has the potential to improve survival in patients with H-ARS by facilitating recovery of blood cells that are important in helping the body’s immune system fight infection.
Efficacy studies of Leukine could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons and approval of this use was based on government-sponsored efficacy studies conducted in animals. Leukine (7 mcg/kg per day) or placebo was initiated 48 hours after exposure to myelosuppressive doses of radiation expected to be fatal to 50% to 60% of nonhuman primates at day 60, without requiring supportive whole blood transfusions or individualized antibiotics (36 animals per group). Leukine improved survival by 85% (78% versus 42%; P = 0.0018) at day 60. In addition, in an exploratory cohort that received higher radiation exposures, myelosuppressive doses to be fatal in 70% to 80% of nonhuman primates at day 60, Leukine was also shown to improve survival: 61% survival (11 of 18) in the Leukine group compared to 17% survival (three of 18) in the control group.
Clinical studies of Leukine in patients undergoing autologous or allogeneic bone marrow transplantation who showed improvements in recovery of white blood cells, reduced incidence of severe and life-threatening infections, and improved survival were included as supportive data for this indication. In clinical studies of Leukine, the most commonly reported side effects were fever, nausea, diarrhea, and vomiting. Hypersensitivity reactions and infusion-related reactions have been reported with Leukine injection. Patients, particularly those with pre-existing lung disease, should be closely observed for such events.
Source: Partner Therapeutics, June 6, 2018
Olumiant for Rheumatoid Arthritis
The FDA has approved the 2-mg dose of baricitinib (Olumiant, Eli Lilly and Company), a once-daily oral medication for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) inhibitor therapies. Baricitinib may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).
The baricitinib clinical trial program included the RA-BEACON study, a randomized, double-blind, placebo-controlled study in which patients were randomly assigned to receive baricitinib 2 mg, baricitinib 4 mg, or placebo, in addition to conventional DMARDs that they were currently using. This study included 527 patients who had an inadequate response or intolerance to one or more TNF inhibitor therapies. Patients could have had prior therapy with other DMARDs.
The study results showed that significantly higher American College of Rheumatology 20% improvement criteria (ACR20) response rates and improvement in all individual ACR20 component scores were observed at week 12 with baricitinib. The study found that patients treated with baricitinib had significantly higher rates of ACR20 response versus placebo-treated patients at week 12 (49% of baricitinib-treated patients versus 27% of placebo-treated patients). Baricitinib also demonstrated early symptom relief, with ACR20 responses seen as early as week 1. Patients treated with baricitinib reported significant improvements in physical function based on the Health Assessment Questionnaire Disability Index, recording an average score of 1.71 before treatment and 1.31 at week 12 (compared with placebo-treated patients who recorded an average score of 1.78 before treatment and 1.59 at week 12).
Baricitinib is approved with a boxed warning for the risk of serious infections, malignancies, and thrombosis.
According to Lilly, baricitinib will launch in the U.S. by the end of the second quarter of 2018. The price of baricitinib will be 60% less than the leading TNF inhibitor.
Source: Eli Lilly and Company, June 1, 2018
Ertapenem for Bacterial Infections
ACS DOBFAR has received FDA approval to market ertapenem for injection, 1 g (base)/single-dose vial, the generic form of Ivanz (Merck). Ertapenem is a penem antibacterial used to treat moderate-to-severe infections, including complicated intra-abdominal, skin and skin structure, urinary tract, and pelvic infections, and community-acquired pneumonia. It is also indicated for prophylaxis of surgical-site infection following elective colorectal surgery.
Source: FDA, April 16, 2018
Everolimus for Organ Rejection
West-Ward Pharmaceuticals has received FDA approval for everolimus tablets, 0.25 mg, 0.5 mg, and 0.75 mg. Everolimus is used for organ rejection prophylaxis in renal transplant patients with low-to-moderate immunologic risk, in combination with basiliximab induction and reduced doses of cyclosporine and corticosteroids. Everolimus is the generic version of Zortress (Novartis).
Source: FDA, April 12, 2018
New Tafinlar–Mekinist Uses
The FDA has approved dabrafenib (Tafinlar) in combination with trametinib (Mekinist), both Novartis products, for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutation, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. In addition, the agency approved the combination for the treatment of anaplastic thyroid cancer (ATC) that cannot be removed by surgery or has spread to other parts of the body, and is BRAF V600E mutation-positive.
Adverse events (AEs) in the clinical trials were consistent with other dabrafenib-plus-trametinib studies, and no new safety signals were reported. Of patients treated with the combination, 97% experienced an AE, 41% had grade 3–4 AEs, and 26% had AEs leading to treatment discontinuation (versus 88%, 14%, and 3%, respectively, with placebo).
Dabrafenib plus trametinib is also approved for BRAF V600E mutation-positive non–small-cell lung cancer.
Source: Novartis, April 30, 2018; and FDA, May 4, 2018
Fingolimod for MS in Children
An expanded indication for fingolimod (Gilenya, Novartis) has been approved by the FDA for the treatment of relapsing multiple sclerosis (MS) in children and adolescents 10 years of age and older. This is the first FDA approval of a drug to treat MS in pediatric patients.
Most people with MS experience their first symptoms, such as vision problems or muscle weakness, between the ages of 20 and 40 years. Two to five percent of people with MS have symptom onset before 18 years of age and estimates suggest that 8,000 to 10,000 children and adolescents in the U.S. have this disease.
The clinical trial evaluating the effectiveness of fingolimod in treating pediatric patients with MS included 214 evaluated patients 10–17 years of age and compared fingolimod with another MS drug, interferon beta-1a. In the study, 86% of patients receiving fingolimod remained relapse-free after 24 months of treatment, compared with 46% of those receiving interferon beta-1a.
The side effects of fingolimod in pediatric trial participants were similar to those seen in adults. The most common side effects were headache, liver enzyme elevation, diarrhea, cough, flu, sinusitis, back pain, abdominal pain, and pain in extremities.
Fingolimod was approved by the FDA in 2010 to treat adults with relapsing MS.
Source: FDA, May 11, 2018
First-Line Darzalex For Multiple Myeloma
The FDA has approved the use of daratumumab (Darzalex, Genmab) in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for auto logous stem cell transplant (ASCT).
The approval was based on data from a phase 3 study that showed a reduction of the risk of disease progression or death by 50% (hazard ratio, 0.50; 95% confidence interval, 0.38–0.65; P < 0.0001) in patients with newly diagnosed multiple myeloma ineligible for ASCT when daratumumab is combined with VMP. The safety of daratumumab combination therapy was consistent with the known safety profiles of daratumumab monotherapy and of therapy with bortezomib, melphalan, and prednisone, respectively.
Daratumumab is the first monoclonal antibody to receive FDA approval to treat multiple myeloma and is the first human CD38 monoclonal antibody to reach the market. In August 2012, Genmab granted Janssen Biotech, Inc., an exclusive worldwide license to develop, manufacture, and commercialize daratumumab.
Source: Genmab, May 8, 2018
Xeljanz for Ulcerative Colitis
The FDA has expanded the approval of tofacitinib (Xeljanz, Pfizer) to include adults with moderately to severely active ulcerative colitis (UC). Tofacitinib is the first oral medication approved for chronic use in this indication. Other FDA-approved treatments for the chronic treatment of moderately to severely active UC must be administered through an intra venous infusion or subcutaneous injection.
The efficacy of tofacitinib for the treatment of moderately to severely active UC was demonstrated in three controlled clinical trials. This included two eight-week placebo-controlled trials that demonstrated that 10 mg of tofacitinib given twice daily induces remission in 17% to 18% of patients by week 8. In a placebo-controlled trial among patients who achieved a clinical response by week 8, tofacitinib, at a 5-mg or 10-mg dose given twice daily, was effective in inducing remission by week 52 in 34% and 41% of patients, respectively. Among patients who achieved remission after eight weeks of treatment, 35% and 47% achieved sustained corticosteroid-free remission when treated with 5 mg and 10 mg, respectively.
The safety of chronic use of tofacitinib for UC was studied in the 52-week placebo-controlled trial. Additional supportive safety information was collected from patients who received treatment in an open-label long-term study.
The most common adverse events associated with tofacitinib treatment for UC were diarrhea, elevated cholesterol levels, headache, herpes zoster, increased blood creatine phosphokinase, naso pharyngitis, rash, and upper respiratory tract infection. Less common serious adverse events included malignancy and serious infections such as opportunistic infections. Tofacitinib has a boxed warning for serious infections and malignancy. Patients treated with tofacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. Lymphoma and other malignancies have been observed in patients treated with tofacitinib.
Tofacitinib was previously approved in 2012 for rheumatoid arthritis and in 2017 for psoriatic arthritis.
Source: FDA, May 30, 2018
FDA REVIEW ACTIVITIES
Breakthrough Therapy Status
Pitolisant for Narcolepsy
Harmony Biosciences has received FDA breakthrough therapy and fast-track designations for pitolisant for the treatment of cataplexy in patients with narcolepsy. Fast-track designation was granted for pitolisant for the treatment of excessive daytime sleepiness in patients with narcolepsy and treatment of cataplexy in patients with narcolepsy.
About one in 2,000 Americans has narcolepsy, a neurological disease of sleep–wake state instability, characterized by excessive daytime sleepiness and elements of REM sleep (e.g., cataplexy, sleep paralysis, hallucinations) intruding into wakefulness. In most patients, it is caused by the loss of hypocretin, a neuropeptide in the brain that supports sleep–wake state stability.
Pitolisant, the first selective histamine H3-receptor antagonist/inverse agonist, enhances the activity of histaminergic neurons in the brain, which function to improve a patient’s wakefulness and inhibit attacks of cataplexy.
Harmony has opened enrollment for the Pitolisant Expanded Access Clinical Evaluation (PEACE) program for adult patients in the U.S.
Source: Harmony Biosciences, May 21, 2018
Xalkori for NSCLC and ALCL
The FDA has granted crizotinib (Xalkori, Pfizer) two breakthrough therapy designations. One is for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) with MET exon 14 alterations whose disease progressed on or after platinum-based chemotherapy, and the other is for the treatment of patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive.
MET exon 14 alterations occur in approximately 3% of NSCLC tumors. Anaplastic large cell lymphoma is a rare type of non-Hodgkin’s lymphoma, divided into ALK-positive or ALK-negative disease. Despite the activity of chemotherapy, many patients with ALCL relapse or require alternative treatment approaches.
Crizotinib is currently approved for patients with metastatic NSCLC whose tumors are ALK-positive or ROS1-positive. Crizotinib became a first-line standard of care for ALK-positive metastatic NSCLC in its first approved indication. It is the only FDA-approved treatment indicated for both ALK-positive and ROS1-positive metastatic NSCLC. If approved in patients with metastatic NSCLC with MET exon 14 alterations, crizotinib will be the only tyrosine kinase inhibitor with demonstrated efficacy in three separate biomarker-driven indications in NSCLC.
The designation for patients with metastatic NSCLC with MET exon 14 alterations was supported by results from two studies that showed compelling anti tumor activity in pediatric and adult patients who received crizotinib.
Source: Pfizer, May 29, 2018
Tafamidis for Transthyretin Cardiomyopathy
Pfizer’s Tafamidis has received a breakthrough therapy designation for the treatment of patients with transthyretin cardiomyopathy, a rare, fatal, and underdiagnosed condition associated with progressive heart failure.
The prevalence of transthyretin cardiomyopathy is unknown; however, it is estimated that fewer than 1% of people with the disease are diagnosed. The average life expectancy is three to five years from diagnosis. There are no approved pharmacological treatments specifically indicated for this disease.
The FDA’s decision is supported by topline results from the phase 3 transthyretin cardiomyopathy study, in which tafamidis demonstrated a statistically significant reduction in the combination of all-cause mortality and frequency of cardiovascular-related hospitalizations.
Source: Pfizer, May 23, 2018
Lenti-D for CALD
The FDA has granted a breakthrough therapy designation to Bluebird Bio for Lenti-D, a treatment for patients with cerebral adrenoleukodystrophy (CALD), a life-threatening hereditary neurological disorder.
Also known as Lorenzo’s oil disease, CALD affects an estimated one in every 21,000 boys worldwide; in 40% of them, the disease progresses to the cerebral form. In CALD, the protective sheath of the nerve cells in the brain responsible for thinking and muscle control breaks down.
Currently, the only therapeutic option for patients with CALD is allogeneic hemato poietic stem cell transplant (HSCT); a beneficial effect has been reported if HSCT is performed early in the course of CALD progression. Potential complications, which can be fatal, include graft failure, graft-versus-host disease, and opportunistic infections, particularly when cells from a donor who is not a matched, unaffected sibling are used.
Treatment with Lenti-D modifies a patient’s own immature bone marrow cells to include a functional copy of the ABCD1 gene to express functional ALD protein (ALDP), which is lacking in patients with CALD. When the modified cells are provided back to the patient, they develop into different cell types, including brain cells. Expression of ALDP in the brain may reduce the accumulation of very-long-chain fatty acids, which are thought to contribute to neurodegeneration.
The breakthrough therapy designation is supported by preliminary data from the ongoing phase 2/3 Starbeam Study. The study found that 15 of 17 patients infused with Lenti-D remained alive and free of major functional disabilities two years post-treatment. The safety profile of Lenti-D is consistent with that of myeloablative chemotherapy. No engraftment failure, graft-versus-host disease, or treatment-related mortality occurred, nor was there any evidence of insertional oncogenesis. Patients who complete the Starbeam study subsequently enroll in LTF-304, a long-term follow-up study.
Source: Bluebird Bio, May 23, 2018
Priority Review Designations
Gilteritinib for R/R AML
The FDA has granted priority review to the new drug application (NDA) for gilteritinib (Astellas) for the treatment of adults who have relapsed/refractory (R/R) acute myeloid leukemia (AML) with an FLT3 mutation.
Approximately 30% of AML patients have FLT3 mutations, which are often associated with poor outcomes. Many patients with this condition relapse after treatment or don’t respond to available treatments. Currently, no FLT3-targeting agents are approved for FLT3 mutation-positive R/R AML.
Gilteritinib is an investigational compound with demonstrated inhibitory activity against FLT3 internal tandem duplication as well as FLT3 tyrosine kinase domain, two common types of FLT3 mutations found in approximately one-third of patients with AML. Gilteritinib has also demonstrated inhibition of the AXL receptor in AML cell lines.
The NDA is based on an ongoing phase 3 trial comparing gilteritinib or salvage chemotherapy in adults with FLT3 mutation-positive R/R AML.
The FDA’s Prescription Drug User Fee Act goal date is November 29, 2018.
Source: Astellas, May 29, 2018
Larotrectinib for TRK Fusion Cancer
Larotrectinib (Bayer/Loxo Oncology) has been granted priority review by the FDA for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. The agent is an investigational tropomyosin receptor kinase (TRK) inhibitor.
TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein. The altered protein becomes active and triggers a signal cascade. These proteins become the primary oncogenic drivers of the spread and growth of tumors. NTRK gene fusion has been identified in various adult and pediatric solid tumors with varying frequencies.
The FDA has set a Prescription Drug User Fee Act target action date of November 26, 2018.
Source: Bayer/Loxo, May 29, 2018
Keytruda Combo for Metastatic Nonsquamous NSCLC
The FDA has granted priority review to a supplemental biologics license application for pembrolizumab (Keytruda, Merck), an anti-programmed death-1 therapy. The application seeks approval for pembrolizumab in combination with pemetrexed (Alimta, Lilly USA) and platinum chemotherapy (carboplatin or cisplatin) as a first-line treatment for patients with metastatic nonsquamous non–small-cell lung cancer (NSCLC). A Prescription Drug User Fee Act date has been set for September 23, 2018.
The application is based on overall survival and progression-free survival data from KEYNOTE-189, the confirmatory trial for KEYNOTE-021 (Cohort G).
Source: Merck, April 30, 2018
Tecentriq Combo for Metastatic Nonsquamous NSCLC
The supplemental biologics license application for Genentech’s atezolizumab (Tecentriq) in combination with bevacizumab (Avastin, Genentech), paclitaxel, and carboplatin for first-line treatment of metastatic nonsquamous non–small-cell lung cancer (NSCLC) has been granted priority review by the FDA.
Atezolizumab is currently approved for patients with metastatic NSCLC whose disease progressed during or following platinum-containing chemotherapy, and has progressed on a targeted therapy if their tumor has ALK or EGFR gene abnormalities.
The supplemental application is based on results from the phase 3, multicenter, open-label, randomized IMpower150 trial of atezolizumab in combination with carbo platin and paclitaxel with or without bevacizumab in people with stage IV nonsquamous NSCLC who had not been treated with chemotherapy.
Source: Genentech, May 7, 2018
Cemiplimab for Advanced CSCC
The FDA has granted priority review to cemiplimab (Sanofi/Regeneron), a treatment for patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for surgery. The target action date for the FDA decision is October 28, 2018.
Although CSCC has a good prognosis when caught early, the cancer can prove especially difficult to treat and is deadly when it is advanced. There are no FDA-approved treatments for advanced CSCC.
Cemiplimab is an investigational human monoclonal antibody targeting the checkpoint inhibitor programmed death-1. The submission is based on a phase 2, single-arm, open-label clinical trial of cemiplimab for advanced CSCC and on phase 1 data from two advanced CSCC expansion cohorts. Both trials enrolled patients with metastatic CSCC and patients with locally advanced CSCC who were not candidates for surgery.
Source: Sanofiand Regeneron, April 30, 2018
SCY-078 for Vulvovaginal Candidiasis
The FDA has granted both qualified infectious disease product and fast-track designations for the oral formulation of SCY-078 (Scynexis, Inc.), a novel anti-fungal agent for the treatment of vulvovaginal candidiasis (VVC) and for the prevention of recurrent VVC. VVC, commonly known as a yeast infection, is usually caused by Candida albicans, and typical symptoms include pruritus, vaginal soreness, irritation, and abnormal vaginal discharge.
SCY-078 is an investigational anti-fungal agent that is a semisynthetic derivative of the natural product enfumafungin. The agent is the first representative of a novel class of structurally distinct glucan synthase inhibitors called triterpenoids. It combines the well-established activity of glucan synthase inhibitors with the potential flexibility of having intravenous and oral formulations. SCY-078 is currently in development for the treatment of fungal infections caused primarily by Candida (including C. auris) and Aspergillus species. It has demonstrated a broad spectrum of antifungal activity in vitro and in vivo against multidrug resistant pathogens, including azole- and echino-candin-resistant strains. The FDA has granted QIPD and fast-track designations for the formulations of SCY-078 for the indications of invasive candidiasis (IC) (including candidemia), invasive aspergillosis (IA), and VVC, and has granted orphan drug designation for the IC and IA indications.
Source: Scynexis, Inc., May 1, 2018
ACE-083 for FSHD
Acceleron Pharma, Inc., has received fast-track designation for ACE-083, a treatment for patients with facioscapulohumeral muscular dystrophy (FSHD).
FSHD is a serious neuromuscular disorder for which there are currently no approved therapies. The disease is typically diagnosed by a characteristic pattern: debilitating skeletal muscle weakness and loss, beginning with the face and upper body and progressing to the lower body in a muscle-by-muscle fashion.
ACE-083 is based on the naturally occurring protein follistatin, which uses the “myostatin+” approach to inhibit multiple transforming growth factor-beta ligands. It is designed to have a concentrated effect along targeted muscles to maximize growth and strength.
ACE-083 is being evaluated in two phase 2 trials: one in FSHD and one in Charcot–Marie–Tooth disease.
Source: Acceleron, May 1, 2018
5F9 for Specific Lymphomas
The FDA has granted two fast-track designations to 5F9 (Forty Seven, Inc.) for the treatment of two forms of B cell non-Hodgkin’s lymphoma (NHL): relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL) and follicular lymphoma (FL).
The natural progression of B cell NHL varies widely across multiple forms, including aggressive forms, such as DLBCL, and slower-growing or indolent forms, such as FL. Without treatment, survival of aggressive NHL is only a few months. 5F9 is a monoclonal antibody against CD47 designed to block the “don’t-eat-me” signal used by cancer cells to avoid being ingested by macrophages.
The designations were based on data from an open-label, multicenter phase 1b/2 clinical trial of 5F9 in combination with rituximab (Rituxan, Genentech) in patients with R/R B cell NHL, including DLBCL and FL. 5F9 is also being evaluated as a monotherapy in a phase 1 trial in patients with ovarian cancer and other solid tumors; in combination with azacitidine in a phase 1/1b trial in patients with refractory acute myeloid leukemia; and in combination with cetuximab (Erbitux, Lilly USA) in a phase 1b/2 trial in patients with advanced R/R solid tumors, including colorectal cancer.
Source: Forty Seven, Inc., May 3, 2018
RGX-121 for MPS II
Regenxbio, Inc., has been granted an FDA fast-track designation for RGX-121, a novel, one-time investigational treatment for mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome.
MPS II is a rare x-linked recessive genetic disease caused by deficiency of I2S, an enzyme required for the breakdown of polysaccharides in the lysosomes. These polysaccharides, called glycosaminoglycans, accumulate in tissues of MPS II patients, resulting in characteristic storage lesions and diverse clinical signs and symptoms, such as neural cell death, excess fluid in the brain, spinal cord compression, and cognitive impairment.
The current disease-modifying therapy for MPS II is enzyme replacement therapy with a recombinant form of human I2S administered intravenously (IV). However, IV enzyme therapy does not treat the central nervous system (CNS) manifestations of MPS II. RGX-121 is being developed as a one-time, direct-to-CNS treatment for MPS II that includes the NAV AAV9 vector encoding for human I2S. Direct delivery of the enzyme could provide a permanent source of secreted I2S beyond the blood–brain barrier, allowing for long-term cross-correction of cells throughout the CNS. This strategy could also provide rapid I2S delivery to the brain, potentially preventing the progression of cognitive deficits common in MPS II patients.
Source: Regenxbio, Inc., May 2, 2018
Rare Pediatric Disease Designation
Diacerein Ointment for Epidermolysis Bullosa
Castle Creek Pharmaceuticals has received a rare pediatric disease designation for CCP-020 (diacerein 1% ointment) for the treatment of epidermolysis bullosa (EB), a genetic condition that leads to extremely fragile skin resulting in mild-to-severe blistering, skin erosion, and peeling of the epidermis layers in response to minor injury. There are currently no approved treatment options for any form of EB.
CCP-020 is an ointment formulation of 1% diacerein developed for topical application. Diacerein is hydrolyzed to rhein in the epidermis and dermis following administration and is believed to block an inflammatory signaling pathway associated with EB simplex (EBS), a subtype of EB, strengthening epidermal tissue and healing skin blisters.
Source: Castle Creek Pharmaceuticals, May 16, 2018
DRUG SAFETY ISSUES
Benzocaine Teething Products
The FDA has warned consumers that over-the-counter (OTC) teething products containing benzocaine pose a serious risk to infants and children. The agency has announced that OTC oral health products containing the pain reliever benzocaine for the temporary relief of sore gums due to teething in infants or children should no longer be marketed and is asking companies to stop selling these products for such use. If companies do not comply, the FDA will initiate a regulatory action to remove these products from the market. In addition, the agency is requesting that companies add new warnings to all other benzocaine oral health products to describe certain serious risks.
This new warning builds on the agency’s previous warnings about risks associated with benzocaine products for methemoglobinemia. This dangerous condition is the result of elevated levels of methemoglobin in the blood and it can lead to death. It causes the amount of oxygen carried through the blood to be greatly reduced. The FDA also outlined these safety concerns in letters that the agency sent to manufacturers of these products. The agency made specific recommendations to manufacturers in order to protect patients and make sure the most up-to-date drug safety information will appear on drug labels.
Source: FDA, May 23, 2018
Dolutegravir and Risk of Neural Tube Birth Defects
The FDA is alerting the public that serious cases of neural tube birth defects involving the brain, spine, and spinal cord have been reported in babies born to women treated with dolutegravir used to treat human immunodeficiency virus (HIV). Preliminary results from an ongoing observational study in Botswana found that women who received dolutegravir at the time of becoming pregnant or early in the first trimester appear to be at higher risk for these defects.
The agency is investigating this new safety issue and will update the public when more information is available.
Dolutegravir is an FDA-approved antiretroviral medicine used in combination with other antiretroviral medicines to treat HIV. Dolutegravir is available as a single-ingredient product under the brand name Tivicay and as a fixed dose combination tablet with other HIV medicines under the brand names Juluca and Triumeq. All are products from ViiV Healthcare.
Source: FDA, May 18, 2018
First Artificial Iris in U.S
The FDA has approved the first stand-alone prosthetic iris (CustomFlex, HumanOptics AG) in the U.S., a surgically implanted device to treat adults and children whose iris is completely missing or damaged due to congenital aniridia or other damage to the eye.
Congenital aniridia is a rare genetic disorder in which the iris is completely or partially absent. It affects approximately one in 50,000 to 100,000 people in the U.S. The iris controls the amount of light entering the eye, and those with aniridia have sensitivity to light and other severe vision problems. In addition to congenital aniridia, the artificial iris is indicated to treat iris defects due to other reasons or conditions, such as albinism, traumatic injury, or surgical removal due to melanoma.
The artificial iris is made of thin, foldable medical-grade silicone and is custom-sized and colored for each individual patient. A surgeon makes a small incision, inserts the device under the incision, unfolds it, and smooths out the edges using surgical instruments. The prosthetic iris is held in place by the anatomical structures of the eye or, if needed, by sutures.
The CustomFlex artificial iris was approved through a pre-market approval application and was granted a breakthrough device designation.
Source: FDA, May 30, 2018
Hemospray for GI Bleeding
The FDA has permitted marketing of Hemospray (Wilson-Cook Medical, Inc.), a new device used to help control certain types of bleeding in the gastrointestinal (GI) tract.
The Hemospray device is intended to treat most types of upper or lower GI bleeding. The device is an aerosolized spray that delivers a mineral blend to the bleeding site. The device is applied during an endoscopic procedure and can cover large areas, such as large ulcers or tumors. The device is not intended for use in patients with variceal bleeding, which is bleeding that comes from enlarged veins that develop in certain medical conditions such as alcoholic liver disease.
The FDA reviewed the Hemospray device through the de novo pre-market review pathway.
Source: FDA, May 7, 2018
Diagnosis Software For Wrist Fractures
Imagen has received marketing permission from the FDA for OsteoDetect, a type of computer-aided detection and diagnosis software designed to detect wrist fractures in adults.
OsteoDetect analyzes wrist radiographs using an artificial intelligence algorithm to identify and highlight regions of distal radius fracture during the review of posterior–anterior and medial–lateral x-ray images of adult wrists. It is intended for use by clinicians in various settings, including primary care, emergency medicine, urgent care, and specialty care, such as orthopedics. It is an adjunct tool and is not intended to replace a clinician’s review of the radiograph or his or her clinical judgment.
The FDA reviewed the OsteoDetect device through the de novo pre-market review pathway.
Source: FDA, May 24, 2018
Synojoynt Injection For Osteoarthritis
Synojoynt (Teva Pharmaceuticals USA, Inc.) has received FDA approval for the treatment of knee pain associated with osteoarthritis. The product is provided in a single-use syringe prefilled with a thick substance made of sodium hyaluronate in saline solution for injection in the osteoarthritic knee joint. This substance is similar to hyaluronic acid found in the knee joint space.
Synojoynt is injected by a physician directly into the intra-articular space inside the knee. The treatment consists of three weekly 3-mL doses.
The product is indicated for the treatment of pain in osteoarthritis of the knee in patients who have failed conservative noninvasive treatments, such as physical therapy and simple pain medicines, such as acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen.
Synojoynt is intended to relieve pain associated with osteoarthritis in the knee for up to six months.
In a clinical study with 396 patients, the 197 patients who received Synojoynt had an average reduction in pain scores of 36 mm (on a 500-mm scale) greater than for the 199 patients receiving the saline control. In addition, the average percentage changes in stiffness scores were significantly better for patients receiving Synojoynt (47.4% reduction in stiffness score) in comparison to those patients that received the saline control (35.8% reduction in stiffness score).
The product should not be used in patients who have a known hypersensitivity to hyaluronan preparations or in those with infections or skin disease around the injection site.
Source: FDA, May 8, 2018
DEVICE SAFETY ISSUES
Class I Recalls
HeartWare Ventricular Assist System
Medtronic is recalling the HeartWare HVAD because of the possibility for an interruption to occur in the electrical connection between the system’s power source (battery, AC adapter, or DC adapter) and the HVAD controller. This interruption to the electrical connection, which occurs when the power source is still physically connected, is caused by oxidation on the connecting surfaces between the power source connector and the controller’s power source socket. The FDA has designated this as a class I recall.
Interruptions to the electrical connection could cause unintended intermittent electrical disconnection, which could result in a pump stop. A pump stop could cause patient harm such as exacerbation of heart failure symptoms, or symptoms such as mild weakness, dizziness, anxiety, nausea, loss of consciousness, or death.
The manufacturing and distribution dates included in the recall are from March 2006 to May 2018. All of the more than 204,000 devices in the U.S. are affected and include the following model numbers: controller/controller kits 1400, 1401, 1403, 1407, 1420; DC adapters 1435, 1440; AC adapters 1425, 1430; and battery packs 1650.
This HVAD is indicated for use as a bridge to cardiac transplantation in patients who are at risk of death from end-stage left ventricular heart failure. It functions as a pump that helps the heart deliver blood to the rest of the body. The HeartWare System is designed for in-hospital and out-of-hospital settings, including transportation via fixed-wing aircraft or helicopter. These indications have been expanded to include HVAD use for myocardial recovery, or as destination therapy in patients for whom subsequent transplantation is not planned.
Source: FDA, June 1, 2018
HeartMate 3 Left Ventricular Assist System
Abbott is recalling the HeartMate 3 left ventricular assist system due to a malfunction in the device’s outflow graft assembly that may cause the outflow graft to twist and close up (occlusion) over time. Occlusion of the outflow graft can reduce or stop pump flow and set off a persistent low-flow alarm in the system. A reduction in pumping can lead to serious adverse events such as blood clots and death. The FDA has designated this as a class I recall.
The recall applies to all devices distributed from September 2, 2014, to the present. The model/item numbers include: catalog 106524US (U.S. commercial), 106524 (U.S. Investigational Device Exemption number), and 10652INT (international).
The HeartMate 3 left ventricular assist system helps deliver blood from the heart to the rest of the body. It is used for short-term support of patients who are at risk of death from end-stage left ventricular heart failure, such as patients awaiting a heart transplant. The system includes a blood pump that is implanted in the space around the heart (pericardium) along with an outflow graft that connects the pump to the aorta.
Source: FDA, May 22, 2018
MindFrame Capture LP Revascularization Device
Medtronic is recalling the MindFrame Capture LP revascularization device because there is a risk of the delivery wire breaking or separating during use. The clot retriever could be left inside the patient’s bloodstream, and this or the attempts made to retrieve the device, can lead to further complications including bleeding, additional blockage of blood vessels, more severe stroke symptoms, or death. The FDA has designated this as a class I recall.
The recall affects devices manufactured from February 3, 2016, to January 14, 2018, and distributed from March 18, 2016, to January 17, 2018. The product lots numbers include: 300010, 300011, 300012, 300013, 300014, 300015, 300016, 300017, and 300018.
The MindFrame Capture LP revascularization device is intended to restore blood flow or remove blood clots within a blood vessel in the brain during an acute ischemic stroke in patients who are ineligible for or fail intravenous tissue plasminogen activator therapy.
Source: FDA, May 18, 2018
AirLife Resuscitation Devices And Broselow Convenience Kits
Vyaire Medical is recalling the AirLife resuscitation device and Broselow convenience kit due to an error in its product design that may result in difficulty or the inability to disconnect the mask from the elbow of the resuscitator. The FDA has designated this as a class I recall.
The AirLife resuscitation device and Broselow convenience kit comes fully assembled and ready to use with a cushioned mask, which can be removed to provide continuous ventilation after placement of an advanced airway device. However, the cushioned mask component has the possibility of sticking to the elbow of the resuscitator, making removal of the mask difficult, or unattainable. Difficulty disconnecting the mask from the resuscitator could result in a delay in or inability to provide necessary ventilation to the patient and potentially result in serious patient injury, such as hypoxia or death.
The products being recalled were manufactured from January 2016 to January 2017 and distributed from March 2016 to January 2017. More than 350,000 of these devices are in use in the United States.
The Vyaire Medical AirLife resuscitation device and Broselow convenience kit are manual resuscitation devices used together as one pair to provide constant ventilation to adults and children who are not breathing or cannot adequately breathe on their own following placement of an advanced airway device (tracheal or tracheostomy tube).
Source: FDA, May 11, 2018
Fabius Anesthesia Machines
Dräger Medical is recalling Fabius anesthesia machines due to excessive oil that was not removed at the time of production. Such excess oil may interfere with the position detector of the ventilation motor during operation and may cause ventilation to fail. A halt in ventilation may lead to serious adverse health consequences, including patient injury or death.
The recalled products include the Fabius GS Premium, Fabius Tiro, Fabius Tiro M, and Fabius MRI anesthesia machines. The devices were manufactured June 1, 2017, to November 30, 2017, and distributed July 14, 2017, to December 13, 2017.
Fabius anesthesia machines are inhalation anesthesia machines for use in operating, induction, and recovery rooms at hospitals and in magnetic resonance imaging settings with patients of all ages. They may be used with oxygen, nitrous oxide, and air supplied by a medical gas pipeline system or by externally mounted gas cylinders.
Source: FDA, May 9, 2018