Drug and Device News June 2017
NEW DRUG APPROVALS
Imfinzi for Bladder Cancer
The FDA has granted accelerated approval to durvalumab (Imfinzi, Astra-Zeneca/MedImmune), a human mono-clonal antibody that blocks programmed death ligand-1 (PD-L1), for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or after platinum-containing chemotherapy or whose disease has progressed within 12 months after receiving platinum-containing chemotherapy before or after surgery.
In a phase 1/2 study, durvalumab demonstrated rapid and durable responses, with an objective response rate of 17% in all evaluable patients regardless of PD-L1 status and 26% in patients with PD-L1 high-expressing tumors. In addition, approximately 14% of all evaluable patients achieved a partial response, and 3% achieved a complete response.
Source: AstraZeneca, May 2, 2017
Alunbrig for Lung Cancer
Brigatinib (Alunbrig, Takeda Pharmaceuticals) has received accelerated approval from the FDA for the treatment of patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non–small-cell lung cancer (NSCLC) who have progressed on or are intolerant of crizotinib (Xalkori, Pfizer). The accelerated approval was based on positive data from the phase 2, open-label ALTA trial, which enrolled 222 adults with locally advanced or metastatic ALK+ NSCLC who had progressed during treatment with crizotinib. The patients received either 90 mg brigatinib once daily (n = 112) or 180 mg brigatinib once daily (n = 110) after a seven-day lead-in of 90 mg once daily. The primary efficacy endpoint was the confirmed overall response rate (ORR).
With a median follow-up period of 8.0 months (range, 0.1–20.2 months), the results demonstrated a confirmed ORR of 53% (as assessed by an independent review committee [IRC]) or 54% (as assessed by the investigator) among the patients who received the recommended brigatinib dosing regimen of 90 mg once daily, increased to 180 mg once daily. In this group, the median duration of response was 13.8 months by IRC assessment or 11.1 months by investigator assessment.
Source: Takeda, April 28, 2017
Tymlos for Osteoporosis
The FDA has given a “thumbs-up” to abaloparatide injection (Tymlos, Radius Health) for the treatment of post-menopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed on or are intolerant of other available osteoporosis therapies.
An 18-month, phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of abaloparatide (80 mcg) in reducing the risk of vertebral and nonvertebral fractures in 2,463 postmenopausal women with osteoporosis. Compared with placebo, abaloparatide reduced the relative risks of new vertebral and nonvertebral fractures by 86% and 43%, respectively.
Source: Radius Health, April 28, 2017
Rydapt for AML and Blood Disorders
The FDA has cleared midostaurin (Rydapt, Novartis) for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who have the FLT3 gene mutation, in combination with chemotherapy. The drug is approved for use with a companion diagnostic, the LeukoStrat CDx FLT3 mutation assay (Invivoscribe Technologies), which is used to detect the FLT3 mutation in patients with AML.
Midostaurin, a kinase inhibitor, blocks several enzymes that promote cell growth. If the FLT3 mutation is detected in blood or bone marrow samples using the LeukoStrat CDx FLT3 mutation assay, the patient may be eligible for treatment with midostaurin in combination with chemotherapy.
Midostaurin was also approved for the treatment of adults with the following rare blood disorders: aggressive systemic mastocytosis, systemic mastocytosis with associated hematologic neoplasm, and mast cell leukemia.
Source: Novartis, April 27, 2017
Brineura for Pediatric Brain Disorder
Cerliponase alfa (Brineura, BioMarin Pharmaceuticals) has secured FDA approval to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency. Cerliponase alfa is the first treatment indicated for children with CLN2 disease, a form of Batten disease.
CLN2 affects fewer than one in one million United States residents, many of whom are undiagnosed. Each year, approximately 20 children are born in the U.S. with CLN2 disease. These affected children lose the ability to walk and talk completely around 6 years of age. During the later stages of the disease, feeding and tending to everyday needs becomes very difficult, with death often occurring between 8 and 12 years of age.
Cerliponase alfa is a recombinant form of TPP1, the enzyme that is deficient in patients with CLN2 disease. It is an enzyme-replacement therapy designed to restore TPP1 enzyme activity and to break down the storage materials that cause CLN2 disease. In order to reach the cells of the brain and central nervous system, the treatment is delivered directly into the cerebrospinal fluid using patented technology.
Source: BioMarin, April 27, 2017
Abuse-Deterrent RoxyBond for Pain
The FDA has given the green light to RoxyBond tablets (oxycodone hydrochloride [CII], Inspirion Delivery Sciences) for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. The product is an abuse-deterrent oral formulation of oxycodone that uses physical and chemical barriers to deter abuse, without the use of aversive agents or opioid antagonists.
RoxyBond is the first immediate-release opioid analgesic approved with labeling describing its abuse-deterrent properties. In vitro data have demonstrated that the product has physico-chemical properties that are expected to make abuse via injection difficult. However, abuse by the intranasal, oral, and intravenous routes is still possible.
Source: Inspirion, April 26, 2017
The FDA has cleared Renflexis (infliximab-abda, Samsung Bioepis/Merck), a biosimilar product referencing Remicade (infliximab, Janssen), across all eligible indications. Renflexis is approved for reducing signs and symptoms in patients with adult and pediatric Crohn’s disease, adult ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and for the treatment of adult plaque psoriasis. The product is marketed in the United States by Merck.
Source: Samsung Bioepis, April 24, 2017
Ingrezza for Dyskinesia
The FDA has given the nod to valbenazine capsules (Ingrezza, Neurocrine Biosciences) for the treatment of adults with tardive dyskinesia. It is the first drug approved by the FDA for this condition.
Tardive dyskinesia is a neurological disorder characterized by repetitive involuntary movements, usually of the jaw, lips, and tongue. Some affected people also experience involuntary movement of the extremities or difficulty breathing.
The efficacy of valbenazine was demonstrated in a placebo-controlled trial with 234 patients. After six weeks, participants treated with valbenazine showed improvement in the severity of abnormal involuntary movements compared with those who received placebo.
Source: FDA, April 11, 2017
Austedo for Huntington’s Chorea
The FDA has approved deutetrabenazine (Austedo, Teva Pharmaceutical Industries) for the treatment of patients with chorea associated with Huntington’s disease (HD). Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor for oral administration that binds to melanin-containing tissues. It is the first new treatment for Huntington’s chorea in almost a decade.
The FDA’s approval was based on results from a phase 3 study that assessed the safety and efficacy of deutetrabenazine in reducing chorea in 90 ambulatory patients with HD. Total maximal chorea scores for patients receiving deutetrabenazine improved by approximately 4.4 units from baseline to the maintenance period (the average of week 9 and week 12) compared with approximately 1.9 units in the placebo group (P < 0.0001).
Source: Teva, April 3, 2017
Tagrisso for Lung Cancer
The FDA has granted full approval for osimertinib tablets (Tagrisso, Astra-Zeneca), 80 mg, for the once-daily treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non–small-cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed during or after EGFR tyrosine kinase inhibitor therapy. Osimertinib received accelerated approval for this indication in 2015 based on the tumor response rate and the duration of response.
Osimertinib is the only medication currently approved in the U.S. for patients with NSCLC who have tested positive for the EGFR T790M mutation.
The FDA’s full approval was based on data from a phase 3 trial in which osimertinib significantly improved progression-free survival (PFS) compared with platinum-based doublet chemotherapy, providing 10.1 months of median PFS versus 4.4 months with chemotherapy (P < 0.001).
Source: AstraZeneca, March 31, 2017
Jubilant Life Sciences has received final approval of its abbreviated new drug application for celecoxib capsules, 50 mg, 100 mg, 200 mg, and 400 mg—a generic version of Celebrex (Pfizer), which is used for the treatment of patients with osteoarthritis or rheumatoid arthritis.
Source: Jubilant Life Sciences, April 11, 2017
Stivarga for Liver Cancer
The FDA has expanded the approved use of regorafenib (Stivarga, Bayer Healthcare) to include patients with hepatocellular carcinoma who have been treated with sorafenib. It was the first new FDA-approved treatment for liver cancer in almost a decade.
Regorafenib is a kinase inhibitor that works by blocking several enzymes that promote cancer growth, including enzymes in the vascular endothelial growth factor pathway. Regorafenib is also approved for the treatment of patients with colorectal cancer and gastrointestinal stromal tumors that are no longer responding to previous treatments.
Source: Bayer, April 27, 2017
Tecentriq for Advanced Bladder Cancer
The FDA has granted accelerated approval to atezolizumab (Tecentriq, Genentech), a monoclonal antibody designed for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. It was the third approval for atezolizumab in less than a year.
The product was previously approved for patients with locally advanced or mUC who have disease progression during or after platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before or after surgery. It is also indicated for patients with metastatic non–small-cell lung cancer who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities.
Source: Genentech, April 17, 2017
Bunavail for Buprenorphine Induction
The FDA has approved a supplemental new drug application for Bunavail buccal film (buprenorphine/naloxone [CIII], BioDelivery Sciences International), revising the indication to include its use for the initiation of buprenorphine treatment for opioid dependence.
The approval broadens the indication for Bunavail to include induction, or the initial process undertaken when a patient is transitioned from the abused opioid responsible for his or her addiction to the dose of Bunavail, which is intended to provide relief from cravings and withdrawal. Previously, the indication for Bunavail covered only the maintenance treatment phase of opioid-dependence treatment.
Source: BioDelivery Sciences International, May 2, 2017
Thymoglobulin to Prevent Kidney Rejection
The FDA has given the go-ahead to Thymoglobulin (anti-thymocyte globulin [rabbit], Sanofi/Genzyme) for use in conjunction with concomitant immunosuppression for the prevention of acute rejection of a kidney transplant.
The FDA approval was based on data from two studies that compared Thymoglobulin with an interleukin-2 receptor antagonist (IL2RA)—basiliximab (Simulect, Novartis) or daclizumab (Zinbryta, Biogen)—in a total of 508 deceased-donor kidney transplant recipients, with a composite endpoint of biopsy-proven acute rejection, graft loss, death, or lost to follow-up. A pooled analysis of the studies showed a composite endpoint rate of 25% within 12 months after transplantation in the Thymoglobulin group compared with 36% in the IL2RA group.
Source: Sanofi, April 24, 2017
Lucentis for Diabetic Retinopathy
The FDA has approved ranibizumab injection (Lucentis, Genentech) for the monthly treatment of all forms of diabetic retinopathy. With this approval, ranibizumab became the only FDA-approved medication to treat diabetic retinopathy in patients who have been diagnosed either with or without diabetic macular edema (DME), a complication of diabetic retinopathy that causes swelling in the back of the eye.
Ranibizumab was previously approved for patients with DME; wet age-related macular degeneration; macular edema after retinal-vein occlusion; diabetic retinopathy; and myopic choroidal neovascularization.
Source: Genentech, April 17, 2017
Qudexy XR for Migraine
Upsher-Smith Laboratories has received FDA final approval of two supplemental new drug applications (sNDAs) for topiramate extended-release capsules (Qudexy XR) for use as prophylaxis of migraine headache in adults and adolescents 12 years of age and older. Topiramate is the molecule that neurologists prescribe most often for the prevention of migraines.
Upsher-Smith was granted tentative approval of its sNDAs in April 2016 but was not eligible to receive final approval until after the innovator drug’s exclusivity for the adolescent population expired in March 2017. The company plans to evaluate XR topiramate for the prophylaxis of migraine in pediatric patients 6 to 11 years of age.
Source: Upsher-Smith Laboratories, March 30, 2017
Methotrexate Oral Solution for Children
The FDA has cleared Xatmep (Silvergate Pharmaceuticals), the first approved methotrexate oral solution, for use in pediatric patients with acute lymphoblastic leukemia or polyarticular juvenile idiopathic arthritis. The product, which consists of 2.5 mg/mL of methotrexate, requires no preparation, eliminating the need for needles, crushing or splitting tablets, or compounding tablets into a liquid formulation.
Source: Silvergate Pharmaceuticals, April 26, 2017
FDA REVIEW ACTIVITIES
Priority Review Designations
Blincyto for ALL
The FDA has accepted for priority review the supplemental biologics license application for blinatumomab (Blincyto, Amgen), a CD19-directed CD3 bispecific T-cell engager antibody, to include overall survival data from the phase 3 TOWER study. The application also includes new data supporting the treatment of patients with Philadelphia chromosome-positive relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The application aims to expand the indication for blinatumomab to include the treatment of all patients with relapsed or refractory B-cell precursor ALL and supports the conversion of the drug’s accelerated approval to full approval. The target action date is August 14, 2017.
Source: Amgen, March 29, 2017
Opdivo for Colorectal Cancer
The FDA has accepted a supplemental biologics license application that seeks to extend the use of nivolumab (Opdivo, Bristol-Myers Squibb) to patients with mismatch repair-deficient or micro-satellite instability-high metastatic colorectal cancer after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. The FDA granted the application priority review, with an action date of August 2, 2017.
Source: Bristol-Myers Squibb, April 4, 2017
Dextromethadone for Depression
Dextromethadone (Relmada Therapeutics), an investigational N-methyl-D-aspartate receptor antagonist, has won the FDA’s fast-track designation for the adjunctive treatment of patients with major depressive disorder. The new chemical entity is being developed as a rapid-acting oral agent for the treatment of patients with depression, neuropathic pain, and other potential central nervous system pathological conditions.
Source: Relmada Therapeutics, April 13, 2017
Coversin for Hemoglobinuria
The FDA has granted fast-track status to Coversin (Akari Therapeutics) for treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients who have polymorphisms that confer resistance to eculizumab (Soliris, Alexion).
Akari Therapeutics is currently evaluating Coversin in two phase 2 trials. The first study involves patients with PNH who have never received complement-blocking therapy, and the second study involves patients with PNH and C5 polymorphisms conferring resistance to eculizumab.
Source: Akari, March 30, 2017
Breakthrough Therapy Designations
CTL019 for B-Cell Lymphoma
CTL019 (Novartis), an investigational chimeric antigen receptor T-cell (CAR-T) therapy, has received breakthrough therapy status for the treatment of adults with relapsed or refractory (r/r) diffuse large B-cell lymphoma who have failed two or more prior therapies. This is the second indication for which CTL019 has received this designation. The first was for the treatment of r/r B-cell acute lymphoblastic leukemia in pediatric and young adult patients, which has also been granted priority review by the FDA.
Source: Novartis, March 29 and April 18, 2017
RVT-802 for DiGeorge Syndrome
The FDA has granted RVT-802 (Enzyvant) a breakthrough therapy designation as well as a regenerative medicine advanced therapy designation for the treatment of pediatric patients with complete DiGeorge syndrome (cDGS). RVT-802 is an investigational biologic therapy that uses proprietary processes to harvest, culture, and apply allogeneic thymic tissue for the treatment of primary immune deficiency resulting from cDGS. Preliminary clinical results suggest a survival rate of greater than 70% in treated patients. Enzyvant anticipates filing a biologics license application in the first half of 2018.
Source: Enzyvant, April 17, 2017
Evinacumab for Hypercholesterolemia
The FDA has granted breakthrough therapy status to evinacumab (Regeneron Pharmaceuticals) for the treatment of patients with homozygous familial hypercholesterolemia, an inherited disorder that can lead to premature cardiovascular disease due to high levels of low-density lipoprotein-cholesterol.
Source: Regeneron Pharmaceuticals, April 6, 2017
Orphan Drug Designation
PTX-200 for AML
The FDA’s Office of Orphan Products Development has granted orphan drug status to PTX-200 (Prescient Therapeutics) for the treatment of patients with acute myeloid leukemia (AML). PTX-200 inhibits the Akt tumor-survival pathway, which is aberrant in many patients with blood cancers, including 72% of those with AML. A phase 1b/2 clinical trial of PTX-200 is under way.
Source: Prescient Therapeutics, May 1, 2017
Emergency Use Authorization
Gene-RADAR Zika Virus Test
The FDA has issued an emergency use authorization for the Gene-RADAR Zika virus test (Nanobiosym Diagnostics). The test is authorized for the qualitative detection of RNA from Zika virus in human serum from individuals meeting Centers for Disease Control and Prevention Zika virus clinical and/or epidemiologic criteria. The test has not been cleared or approved by the FDA and is only authorized for use for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of in vitro diagnostic tests for the detection of Zika virus and/or the diagnosis of Zika virus infection, unless the authorization is terminated or revoked sooner.
Source: Nanobiosym Diagnostics, April 11, 2017
Xarelto 10-mg Dose for VTE
Janssen Research and Development has submitted a supplemental new drug application to the FDA to update the prescribing information for rivaroxaban (Xarelto) to add a 10-mg dose to reduce patients’ risk of recurrent venous thromboembolism (VTE) after at least six months of standard anticoagulation therapy. If the application is approved, health care professionals who are managing patients with VTE will be able to prescribe either rivaroxaban 10 mg (once daily) or the currently approved 20-mg dose (once daily) after patients have received at least six months of standard anticoagulation therapy. Rivaroxaban currently has six FDA-approved indications, including treating VTE and reducing the risk of recurrent VTE.
Source: Janssen, April 28, 2017
Weight-Loss Data for Saxenda
The FDA has approved an updated product label for liraglutide injection 3 mg (Saxenda, Novo Nordisk), which includes data showing that approximately half of patients treated with liraglutide who lost at least 5% of their body weight after 56 weeks maintained their weight loss for three years. Study participants were adults with obesity (body mass index [BMI] greater than or equal to 30 kg/m2) or excess weight (BMI greater than or equal to 27 kg/m2) with at least one weight-related comorbidity on a reduced-calorie meal plan and increased physical activity.
Source: Novo Nordisk, April 27, 2017
Complete Response Letter
Baricitinib for RA
The new drug application for baricitinib (Eli Lilly/Incyte Corporation) for the treatment of patients with moderate-to-severe rheumatoid arthritis (RA) has been met with a complete response letter from the FDA. The letter indicated that the agency was unable to approve the application in its current form. Specifically, the FDA indicated that additional clinical data were needed to determine the most appropriate doses. The FDA also stated that additional data were necessary to further characterize safety concerns across treatment arms. Lilly and Incyte disagreed with the agency’s conclusions.
Source: Eli Lilly, April 14, 2017
Imbruvica for GVHD
The FDA has accepted for review a supplemental new drug application for the kinase inhibitor ibrutinib (Imbruvica, Janssen/Pharmacyclics) for the treatment of patients with chronic graft-versus-host-disease (GVHD) after the failure of one or more lines of systemic therapy. GVHD is a potential life-threatening consequence of stem cell or bone marrow transplant. No approved treatments or established standards of care are specifically indicated for GVHD in patients who have failed initial steroid therapy.
Source: Janssen, April 4, 2017
Xgeva for Multiple Myeloma
Amgen has submitted a supplemental biologics license application to the FDA for denosumab (Xgeva). The submission seeks to expand the product’s currently approved indication for the prevention of skeletal-related events (SREs) in solid tumors to include patients with multiple myeloma. The application included new data from a pivotal phase 3 trial that compared denosumab with zoledronic acid in the prevention of SREs in adults with newly diagnosed multiple myeloma and bone disease.
Source: Amgen, April 4, 2017
Intravitreal Sirolimus for Uveitis
The FDA has accepted for review the new drug application for intravitreal (IVT) sirolimus (Santen Pharmaceutical) for the treatment of patients with noninfectious uveitis of the posterior segment, a progressive and chronic inflammatory disease of the eye that can lead to vision impairment and blindness. The agency set an action date of December 24, 2017, to complete its review. IVT sirolimus was granted an orphan drug designation in 2011.
Source: Santen Pharmaceutical, April 25, 2107
Fostamatinib for Chronic ITP
Rigel Pharmaceuticals has submitted a new drug application to the FDA for fostamatinib in patients with chronic and persistent immune thrombocytopenia (ITP). Fostamatinib is an oral investigational drug candidate with a mechanism of action designed to inhibit SYK kinase, a key player in the immune process that leads to platelet destruction in ITP.
Source: Rigel Pharmaceuticals, April 17, 2017
Dexycu for Inflammation After Cataract Surgery
Icon Bioscience has submitted a new drug application to the FDA seeking the approval of Dexycu as a long-acting dropless treatment for inflammation associated with cataract surgery, a common postoperative occurrence that can lead to serious complications if left untreated. Dexycu is a biodegradable extended-release formulation of the anti-inflammatory agent dexamethasone that is dispensed into the anterior chamber of the eye at the conclusion of cataract surgery.
Source: Icon Bioscience, April 13, 2017
Vyxeos for AML
Jazz Pharmaceuticals has submitted a new drug application to the FDA for the approval of Vyxeos (cytarabine and daunorubicin) liposome for injection, an investigational treatment for patients with acute myeloid leukemia (AML). The company requested a priority review.
Vyxeos consists of a fixed five-to-one ratio of cytarabine and daunorubicin in a nanoscale delivery complex. Vyxeos received a breakthrough therapy designation in May 2016 for the treatment of adults with therapy-related AML or AML with myelodysplasia-related changes; a fast-track designation for the treatment of elderly patients with secondary AML; and an orphan drug designation for AML.
Source: Jazz Pharmaceuticals, April 3, 2017
DRUG SAFETY ISSUES
Illegal Cancer Treatments
The FDA has issued warning letters to 14 U.S.-based companies illegally selling more than 65 products that fraudulently claim to prevent, diagnose, treat, or cure cancer. The illegally sold products include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostics (such as thermography devices). They include products marketed for use by humans or on pets that make illegal, unproven claims regarding preventing, reversing, or curing cancer, killing or inhibiting cancer cells or tumors, or other similar anti cancer claims, according to the agency.
Source: FDA, April 25, 2017
Codeine and Tramadol in Children and Nursing Mothers
The FDA has restricted the use of codeine and tramadol medications in children. These drugs carry serious risks, including slowed or difficult breathing and death, which appear to be a greater risk in children younger than 12 years of age. These medications should also be limited in some older children. Single-ingredient codeine and all tramadol-containing products are FDA-approved only for use in adults. The FDA is also recommending against the use of codeine and tramadol medications in breast-feeding mothers because of possible harm to their infants. The agency has made several changes to the labels of all prescription medications containing codeine or tramadol.
Source: FDA, April 20, 2017
Isomeric Pharmacy Solutions Recalls All Sterile Products
Isomeric Pharmacy Solutions issued a voluntary recall of all lots of sterile products to the hospital/user level because of lack of sterility assurance. These concerns were brought to Isomeric’s attention during a recent FDA inspection. The sterile products were distributed nationwide between October 4, 2016, and February 7, 2017.
Source: FDA, April 6, 2017
CLINICAL TRIAL NEWS
Brexpiprazole for Dementia-Related Agitation
Positive results have been reported from two phase 3 trials evaluating brexpiprazole (Rexulti, Lundbeck/Otsuka) in the treatment of agitation in patients with Alzheimer’s dementia. Brexpiprazole was approved by the FDA in July 2015 to treat patients with schizophrenia and as an adjunctive treatment for patients with major depressive disorder. Its mechanism of action in these settings is unknown. In both studies, patients treated with brexpiprazole showed significant (P < 0.05) improvements in symptoms of agitation compared with placebo.
Source: Lundbeck, May 2, 2017
CAM2038 for Opioid Use Disorder
Positive results have been reported from a long-term phase 3 trial of CAM2038 (buprenorphine depot, Braeburn Pharma ceuticals/Camurus) in patients with moderate-to-severe opioid use disorder. Efficacy was assessed in a total of 228 patients by weekly and monthly urine toxicology tests. On average, 75% of the urine samples were negative for illicit opioids during treatment with CAM2038 depot injections, and no opioid overdoses were reported.
Source: Braeburn Pharmaceuticals, May 2, 2017
Ocrevus for Multiple Sclerosis
New efficacy analyses from two phase 3 studies have indicated the superiority of ocrelizumab (Ocrevus, Roche/Genentech) over interferon beta-1a (Rebif, EMD Serono) in patients with relapsing or primary progressive forms of multiple sclerosis (RMS). Within the first eight weeks of treatment, ocrelizumab reduced the relapse rate by 55% compared with interferon beta-1a (P = 0.0045) in a pooled exploratory analysis of the trials.
Additional analyses of these studies demonstrated the efficacy of ocrelizumab in patients with early RMS (recently diagnosed and without previous treatment). Ocrelizumab suppressed more than 90% of active magnetic resonance imaging lesions during two years of treatment compared with interferon beta-1a (P < 0.0001) in these patients. In the same patients with early RMS, ocrelizumab also increased the proportion that achieved no evidence of disease activity by 76% compared with interferon beta-1a over two years (P < 0.0001).
Source: Roche, April 26, 2017
Zavicefta for Hospital-Acquired Pneumonia
Results from the pivotal phase 3 REPROVE trial have shown that patients diagnosed with hospital-acquired pneumonia treated with Zavicefta (ceftazidime/avibactam, Pfizer), a fixed-dose combination antibiotic for the treatment of certain gram-negative bacterial infections, or meropenem, a broad-spectrum carbapenem antibiotic currently considered the standard of care, experienced comparable rates of clinical cure at test of cure 21 to 25 days after randomization.
Source: Pfizer, April 24, 2017
Iclaprim for ABSSSI
Positive results have been reported from a global phase 3 study of iclaprim (Motif Bio) in patients with acute bacterial skin and skin-structure infections (ABSSSI). Iclaprim achieved the primary endpoint of noninferiority to vancomycin at the early time point (48 to 72 hours after the start of administration of the study drug) in the intent-to-treat (ITT) patient population. Iclaprim also achieved noninferiority to vancomycin at the test-of-cure endpoint (seven to 14 days after study drug discontinuation) in the ITT patient population.
Iclaprim has shown in vitro activity against gram-positive clinical isolates of many genera of staphylococci, including methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus.
Source: Motif Bio, April 18, 2017
Dasotraline for ADHD
Positive results have been reported from a phase 3 study evaluating dasotraline (Sumitomo Dainippon Pharma), a dopamine–norepinephrine reuptake inhibitor, in children 6 to 12 years of age with attention-deficit/hyperactivity disorder (ADHD). The study met its primary endpoint of a change from baseline at day 15 in ADHD symptoms.
Based on the results, Sunovion Pharmaceuticals, a Sumitomo subsidiary, plans to submit a new drug application to the FDA in 2017 for the treatment of ADHD in both adult and pediatric patients. Sunovion is also developing dasotraline in the U.S. for adults with binge-eating disorder.
Source: Sumitomo Dainippon Pharma, April 12, 2017
Semaglutide for Type-2 Diabetes
Results from the phase 3a SUSTAIN 2–4 trials have demonstrated greater mean reductions in hemoglobin A1c (HbA1c) and body weight with once-weekly semaglutide (Novo Nordisk) compared with sitagliptin, extended-release exenatide, and insulin glargine in adults with type-2 diabetes.
On a background of metformin or metformin plus sulfonylurea, treatment with semaglutide (0.5 mg or 1.0 mg) significantly reduced HbA1c versus all three comparators (P < 0.05). In patients receiving a background of thiazolidinedione (TZD) alone or TZD in combination with metformin or sulfonylurea, semaglutide 1.0 mg significantly reduced HbA1c compared with sitagliptin (P < 0.05).
Source: Novo Nordisk, April 3, 2017
Aries Bordetella Assay
Luminex Corporation has received FDA clearance for the Aries Bordetella Assay for the direct detection and identification of Bordetella pertussis and B. parapertussis nucleic acid in naso-pharyngeal swab specimens obtained from individuals suspected of having a respiratory tract infection attributable to B. pertussis or B. parapertussis.
Source: Luminex, May 3, 2017
Coolief for OA Knee Pain
The FDA has approved the Coolief Cooled Radiofrequency thermal treatment (Halyard Health) for the relief of chronic moderate-to-severe knee pain caused by osteoarthritis (OA). The first radiofrequency treatment to be cleared specifically to relieve OA knee pain, Coolief is a minimally invasive, thermal radiofrequency pain-management system using water-cooled technology to deactivate pain-causing sensory nerves.
Source: Halyard Health, April 20, 2017
Echelon Circular Stapler
The circular anastomosis is one of the most critical steps in cancer surgery and has a high risk for complications, including leaks and bleeding that require reoperation. The FDA has awarded 510(k) clearance to the Echelon Circular Powered Stapler (Ethicon). The device is designed to reduce anastomotic complications in colorectal, gastric, and thoracic cancer surgeries.
Source: Ethicon, April 19, 2017
gammaCore Nerve Stimulation For Headache Pain
The FDA has cleared the use of the gammaCore noninvasive vagus nerve stimulator (electroCore) for the acute treatment of pain associated with episodic cluster headache in adults. The hand-held device, applied at the neck, treats the pain associated with cluster headache through mild transdermal electrical stimulation to the vagus nerve.
In the ACT1 trial, 34% of the 85 patients experienced a reduction in pain with the device compared with 11% of those given placebo (P = 0.008). In the ACT2 trial, which evaluated 182 attacks in 27 patients with episodic cluster headache, 48% of the gammaCore group was pain-free compared with 6% of the placebo group (P = 0.003).
Source: electroCore, April 18, 2017
Locking Lattice Plating System
Additive Orthopaedics has received 510(k) clearance from the FDA for its 3D-printed Locking Lattice Plating System for the stabilization and fusion of fractures, osteotomies, and arthrodesis of small bones. The plates can be implanted either alone with locking or nonlocking screws, or in conjunction with the company’s 3D-printed bone segments through the use of a connection screw. This allows surgeons to mix and match any wedge and plate combination for various procedures.
Source: Additive Orthopaedics, April 13, 2017
Polyethylene Knee Insert
The FDA has approved the E-XPE polyethylene knee insert (United Orthopedic). Designed to provide patients with a knee replacement with a reduced risk of oxidation, the device consists of highly cross-linked polyethylene blended with 0.1% (w/w) vitamin E for wear resistance without compromising oxidative stability and mechanical properties.
Source: United Orthopedic, April 13, 2017
“Fever Scout” Wearable Thermometer
Fever Scout (VivaLnk), a soft, wearable thermometer that continuously measures temperature, has received 510(k) clearance from the FDA. The device allows parents and caregivers to remotely monitor a child or patient’s fever using a smart-phone or tablet. It is made from eSkin, a stretchy, breathable circuit board that is as thin as human skin. The device is available at Best Buy in-store and online.
Source: VivaLnk, April 4, 2017
Bodycad Knee System
Quebec-based Bodycad has received FDA 510(k) clearance for its Bodycad Unicompartmental Knee System, making it the first Canadian company to win FDA clearance for a joint-reconstruction implant system. The Bodycad system uses proprietary 3D renderings of medical images of the patient’s anatomy to restore his or her unique anatomical features and kinematics.
Source: Bodycad, March 29, 2017
DEVICE SAFETY ISSUES
Defibrillators From Abbott Laboratories
The FDA recently sent a warning letter to Abbott Laboratories citing manufacturing flaws in several cardiovascular devices that the company acquired when it purchased St. Jude Medical in January, according to a Reuters report. The affected devices, known as implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators, help pace slow heart rhythms and slow dangerously fast rhythms.
In its communication, the FDA said Abbott failed to disclose at least one death associated with one of the devices. The agency also noted that an inspection of the company’s facility in Sylmar, California, raised questions about the safety of several implantable defibrillators and the Merlin@home monitor, which allows doctors to care remotely for patients with cardiac devices.
The FDA investigation found that lithium batteries in the devices were draining prematurely and that the company had “underestimated the occurrence of the hazardous situation.”
Source: Reuters, April 13, 2017
EpiPen and EpiPen Jr. Autoinjectors
Meridian Medical Technologies, a Pfizer company and Mylan’s manufacturing partner for the EpiPen auto injector, expanded its voluntary recall of select lots of EpiPen and EpiPen Jr. auto-injectors (epinephrine injection, USP) to include additional lots distributed in the United States and other markets. This recall was conducted as a result of the receipt of two previously disclosed reports outside of the U.S. of failure to activate the device due to a potential defect in a supplier component.
The recall affected 0.3-mg and 0.15-mg EpiPen autoinjectors. The recalled products were manufactured by Meridian and distributed by Mylan between December 2015 and July 2016. None of the recalled lots included the authorized generic version of the EpiPen autoinjector, which is also manufactured by Meridian.
Source: FDA, March 31, 2017
MedWatch Safety Alerts
The FDA has issued MedWatch Safety Alerts for the following devices:
- StrataMR adjustable valves and shunts by Medtronic: Potential for underdrainage of cerebrospinal fluid. If left untreated, underdrainage can potentially lead to coma and death. Posted April 8, 2017.
- Newport HT70 and HT70 Plus Ventilators by Medtronic: Potential for ventilator to reset spontaneously during normal operation, without an accompanying alarm. Posted April 5, 2017.
- Class I recall of the Prelude short-sheath introducer by Merit Medical Systems: Tip could enter the patient’s bloodstream, resulting in prolonged procedure times, additional surgery to remove the tip from the patient, blood clots, internal tears, perforation to arteries or veins, excessive bleeding, and death. Posted March 31, 2017.