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P T. 2018;43(11): 648-658, 695

Drug and Device News November 2018

NEW DRUG APPROVALS

Lumoxiti for Hairy Cell Leukemia

The Food and Drug Administration (FDA) has approved moxetumomab pasudotox-tdfk injection (Lumoxiti, AstraZeneca) for intravenous use for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including a purine nucleoside analog. Moxetumomab pasudotox, a CD22-directed cytotoxin, is the first treatment of this type for HCL patients.

HCL is a rare, slow-growing blood cancer in which the bone marrow produces too many B-cell lymphocytes. These extra white blood cells look “hairy” when viewed under a microscope. As the number of leukemia cells increases, fewer healthy white blood cells, red blood cells, and platelets are produced.

The efficacy of moxetumomab pasudotox was studied in a single-arm, open-label clinical trial of 80 patients. The trial measured durable complete response (CR), defined as maintenance of hematologic remission, for more than 180 days after achievement of CR. Thirty percent of patients achieved durable CR, and the overall response rate (partial or complete responses) was 75%.

Common side effects of moxetumomab pasudotox include infusion-related reactions, edema, nausea, fatigue, headache, pyrexia, constipation, anemia, and diarrhea. Moxetumomab pasudotox has a boxed warning about the risks of capillary leak syndrome and hemolytic uremic syndrome. Patients should be made aware of the importance of maintaining adequate fluid intake, and blood chemistry values should be monitored frequently.

The FDA granted this application Fast Track, Priority Review, and Orphan Drug designations.

Source: FDA, September 13, 2018

Vizimpro for NSCLC

The kinase inhibitor dacomitinib (Vizimpro, Pfizer Inc.) has received FDA approval for the first-line treatment of patients who have metastatic non–small-cell lung cancer with epidermal growth-factor receptor exon 19 deletion or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

The safety and efficacy of dacomitinib were demonstrated in the open-label ARCHER 1050 study. A total of 452 patients were randomized 1:1 to dacomitinib or gefitinib (Iressa, AstraZeneca). Median progression-free survival was 14.7 months with dacomitinib compared with 9.2 months for gefitinib.

The most common adverse reactions with dacomitinib were diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus. Serious adverse reactions occurred in 27% of patients treated with dacomitinib; the most common were diarrhea and interstitial lung disease.

Source: Pfizer, September 27, 2018

Xarelto for Chronic Coronary Artery Disease, Peripheral Artery Disease

The FDA has approved rivaroxaban (Xarelto, Janssen Pharmaceutical Companies of Johnson & Johnson) to reduce the risk of major cardiovascular (CV) events in people with chronic coronary or peripheral artery disease (CAD/PAD). The drug is now the first and only factor Xa inhibitor approved for patients with these conditions.

Significant results from the milestone COMPASS trial—a 24% reduction in the risk of major CV events in patients with chronic CAD and/or PAD—led to the new indication. The trial also revealed a 42% reduction in stroke, 22% reduction in CV death, and 14% reduction in heart attack.

COMPASS, a phase 3 clinical study of more than 27,000 patients with chronic CAD or PAD from 33 countries, examined the use of rivaroxaban, alone or combined with aspirin, for the long-term prevention of major adverse CV events, including heart attack, stroke, and CV death. The successful outcome in patients using Xarelto 2.5 mg plus aspirin caused the study to be halted early, in February 2017, based on the recommendation of the Independent Data and Safety Monitoring Board.

Although it is seldom fatal, atherosclerosis is the most common underlying cause of chronic CAD and PAD, which affect 16.5 million and 10 million Americans, respectively. The use of aspirin alone has proved insufficient at preventing the thrombotic risk associated with chronic CAD and PAD.

Source: Drugs.com., October 15, 2018

Yutiq for Chronic Noninfectious Uveitis

The FDA approved Yutiq (Eyepoint Pharmaceuticals) for the treatment of chronic noninfectious uveitis, which affects the posterior part of the eye. The company plans to launch the drug in the first quarter of 2019.

In two randomized, sham injection-controlled, double-masked phase 3 clinical trials, Yutiq (a non-bioerodible, intravitreal micro-insert containing 0.18 mg fluocinolone acetonide) significantly reduced recurrent uveitis flares compared to the sham. The most common adverse reactions were cataract development and an increase in intraocular pressure (IOP).

The first trial reached its principal efficacy endpoint at six months, with 18.4% of the patients treated with Yutiq having had a recurrence of uveitis compared with 78.6% of the control patients. The second trial showed that 21.8% of patients experienced uveitis recurrence at six months compared with 53.8% of control patients. The efficacy in both studies was carried out to 12 months.

Follow-up data from 24 months and 36 months from the first trial are expected to be released by the end of 2018 and the first half of 2019, respectively.

Source: Drugs.com., October 15, 2018

Talzenna for Breast Cancer

The FDA has approved talazoparib (Talzenna, Pfizer Inc.) capsules, 0.25 mg and 1 mg, for adult patients aged 18 years and older with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Patients for therapy should be selected based on an FDA-approved companion diagnostic for talazoparib.

Talazoparib’s efficacy was demonstrated in EMBRACA (NCT01945775), a double-arm, open-label study in 431 patients that measured progression-free survival (PFS) evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A significant improvement in PFS was demonstrated among patients in the talazoparib arm compared with patients in the chemotherapy arm.

Serious adverse reactions reported by patients using talazoparib include Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML). Myelosuppression consisting of anemia, leukopenia/neutropenia, and/or thrombocytopenia has also been reported. Pregnant women are advised that talazoparib can cause fetal harm. Female patients are advised to use effective contraception during treatment and for at least seven months following the last dose of the drug. In addition, male patients with female partners of reproductive potential or who are pregnant are advised to use effective contraception during treatment and for at least four months following the last dose.

Source: FDA, October 16, 2018

Libtayo for Skin Cancer

Cemiplimab-rwlc injection for intravenous use (Libtayo, Regeneron Pharmaceuticals, Inc.) has received FDA approval for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation.

This is the first FDA approval of a drug specifically for advanced CSCC, the second most common cancer in the United States with an estimated annual incidence of approximately 700,000 cases. While most CSCC patients are cured with surgical resection, a small percentage develop advanced disease that no longer responds to local treatments, including surgery and radiation. By blocking the programmed death-1 cellular pathway, cemiplimab may help the body’s immune system fight the cancer.

The safety and efficacy of cemiplimab were studied in two open-label clinical trials. A total of 108 patients (75 with metastatic disease and 33 with locally advanced disease) were included in the efficacy evaluation. The objective response rate (partial or complete) was 47.2% with cemiplimab; responses were ongoing in most of these patients at the time of data analysis.

Common side effects of cemiplimab include fatigue, rash, and diarrhea. The drug must be dispensed with a patient medication guide that describes uses of the drug and its serious warnings. Cemiplimab can cause the immune system to attack normal organs and tissues in any area of the body.

The FDA granted this application Breakthrough Therapy and Priority Review designations.

Source: FDA, September 28, 2018

Copiktra for CLL, SLL, and FL

The FDA has approved duvelisib (Copiktra, Verastem, Inc.) for the treatment of adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies. Duvelisib also received accelerated approval (based on overall response rate) for the treatment of adults with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies.

Duvelisib is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma.

In a randomized, multicenter, open-label trial, 196 adults with CLL or SLL who had at least two prior therapies received duvelisib or ofatumumab (Arzerra, Novartis). Median progression-free survival was 16.4 months for duvelisib versus 9.1 months for ofatumumab. In a single-arm, multicenter trial, the overall response rate in 83 patients with previously treated FL was 42% (1 complete and 34 partial responses).

The most common adverse reactions were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

Duvelisib has a boxed warning for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem is implementing an informational risk evaluation and mitigation strategy (REMS) to provide appropriate dosing and safety information.

The application received Priority Review, Fast Track, and Orphan Drug designations for various indications. Continued approval for the FL indication, which received accelerated approval, may be contingent upon confirmatory trials.

Sources: Verastem, September 24, 2018; Copiktra prescribing information, September 2018

Nuzyra, an Antibiotic

Omadacycline (Nuzyra, Paratek Pharmaceuticals, Inc.) has received FDA approval for the treatment of adults with community-acquired bacterial pneumonia and acute skin and skin-structure infections. A modernized tetracycline, omadacycline is a once-daily intravenous and oral antibiotic that exhibits activity across a spectrum of bacteria, including gram-positive, gram-negative, atypical, and drug-resistant strains.

The approval of omadacycline is supported by multiple clinical trials. Nearly 2,000 adults received omadacycline, which was found to be efficacious and generally safe and well tolerated. As part of the approval, Paratek has agreed to conduct post-marketing studies in community-acquired bacterial pneumonia and pediatrics.

Source: Paratek Pharmaceuticals, October 2, 2018

Tegsedi for Amyloidosis

The FDA has approved inotersen (Tegsedi, Akcea Therapeutics, Inc./Ionis Pharmaceuticals, Inc.) to treat the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adults.

In hATTR amyloidosis, transthyretin (TTR) protein misfolds and accumulates as amyloid deposits throughout the body. Inotersen, an RNA-targeting therapeutic given as a once-weekly subcutaneous injection, reduces the production of TTR protein.

In the phase 3 NEURO-TTR study, treatment with inotersen produced up to a 79% mean decrease from baseline in serum TTR protein in patients regardless of TTR mutation, sex, age, or race. Patients treated with inotersen also experienced significant benefits in quality of life compared to patients treated with placebo.

Inotersen has a boxed warning related to the risk of thrombocytopenia and glomerulonephritis. Enhanced monitoring is required to support early detection and management of these identified risks. Inotersen is being marketed with a risk evaluation and mitigation strategy (REMS). The most common side effects of inotersen include injection-site reactions, nausea, headache, tiredness, thrombocytopenia, and fever.

In April 2018, Akcea licensed the worldwide rights to commercialize inotersen from Ionis.

Source: Akcea Therapeutics/Ionis Pharmaceuticals, October 5, 2018

Revcovi Injection for ADA-SCID

The FDA has approved elapegademase-lvlr injection (Revcovi, Leadiant Biosciences, Inc.), an enzyme replacement therapy, for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.

ADA-SCID is an ultrarare, inherited genetic disorder caused by a deficiency in an essential enzyme, adenosine deaminase (ADA); the disorder is fatal if left untreated. Compromised immune systems leave patients unprotected from infection-producing bacteria, viruses, and fungi. Elapegademase is a PEGylated recombinant adenosine deaminase enzyme that works by supplementing ADA levels.

The approval is based on results from two multicenter, open-label clinical trials in which elapegademase increased ADA activity, reduced concentrations of toxic metabolites that are the hallmark of ADA-SCID, and improved total lymphocyte counts.

The FDA granted this application Fast Track, Priority Review, and Orphan Drug designations.

Source: Leadiant Biosciences, October 5, 2018

Arikayce for Mycobacterium Avium Complex

The FDA has approved amikacin liposome inhalation suspension (Arikayce, Insmed, Inc.) to treat lung disease caused by Mycobacterium avium complex (MAC) in patients who do not respond to conventional treatment.

Patients infected by these bacteria, which are often found in water and soil, can suffer from symptoms such as persistent cough, fatigue, weight loss, night sweats, breathlessness, and coughing up blood. After six months of treatment with Arikayce, 29% of patients showed no increase of mycobacteria for 90 days, compared to only 9% of those who had no treatment.

Arikayce was approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, advanced by Congress to increase the development of drugs to tackle infections lacking effective therapies. Arikayce received Accelerated Approval and Fast Track, Breakthrough Therapy, Priority Review, Orphan Drug, and Qualified Infectious Disease Product designations.

Source: FDA, October 1, 2018

Xyosted Auto-Injector for Testosterone Replacement Therapy

Testosterone enanthate injection (Xyosted, Antares Pharma, Inc.) has become the first FDA-approved subcutaneous testosterone-enanthate product for once-weekly, at-home, self-administration with a single-dose, disposable auto-injector.

Testosterone enanthate is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired). It is approved in three dosage strengths: 50 mg, 75 mg, and 100 mg.

Testosterone enanthate has a boxed warning about the risk of blood pressure increase that can worsen the risk for major adverse cardiovascular events. The most commonly reported adverse events in trials were increased hematocrit, hypertension, prostate-specific antigen increases, injection-site bruising, and headache.

Source: Antares Pharma, October 1, 2018

Ajovy for Migraine Prevention

Fremanezumab-vfrm injection (Ajovy, Teva Pharmaceutical Industries Ltd.) has secured FDA approval for the preventive treatment of migraine in adults. It can be administered in quarterly (675 mg) or monthly (225 mg) regimens.

Fremanezumab, a humanized monoclonal antibody, binds to calcitonin gene-related peptide ligand and blocks its binding to the receptor. It was evaluated in two phase 3, placebo-controlled clinical trials that enrolled patients with disabling migraine, and was studied as both a stand-alone preventive treatment and in combination with oral preventive treatments. Patients experienced a reduction in monthly migraine days during a 12-week period. The most common adverse events were injection-site reactions.

Ajovy’s wholesale acquisition cost is $575 per monthly dose and $1,725 per quarterly dose. Under a savings offer, commercially insured patients may pay as little as nothing on prescriptions until the offer expires.

Source: Teva Pharmaceutical Industries Ltd., September 14, 2018

Seysara for Acne Lesions

The FDA has approved sarecycline (Seysara, Paratek Pharmaceuticals, Inc.) for the treatment of inflammatory lesions of non-nodular, moderate-to-severe acne vulgaris in patients aged nine and older. Sarecycline is a once-daily, oral, narrow-spectrum, tetracycline-derived antibiotic with anti-inflammatory properties for potential use in community settings.

Paratek has licensed U.S. development and commercialization rights of Seysara for acne treatment to Allergan PLC, which has assigned such rights to Almirall S.A.

Source: Paratek Pharmaceuticals, October 2, 2018

Emgality to Prevent Migraine

The FDA has approved galcanezumabgnlm (Emgality, Eli Lilly and Company) 120-mg injection, a once-monthly, self-administered, subcutaneous injection for the preventive treatment of migraine in adults.

The efficacy and safety of galcanezumab were demonstrated in two six-month, phase 3 trials in patients with episodic migraine (EVOLVE-1 and EVOLVE-2) and one three-month, phase 3 trial in patients with chronic migraine (REGAIN). In all three studies, the number of reported migraine headache days per month fell more from baseline for patients receiving galcanezumab 120 mg than for those receiving placebo: −4.7 versus −2.8 in EVOLVE-1; −4.3 versus −2.3 in EVOLVE-2; and −4.8 versus −2.7 in REGAIN, respectively. The most common adverse reactions with galcanezumab were injection-site reactions.

The U.S. list price of Emgality (a calcitonin gene-related peptide antagonist) is $575 once monthly ($6,900 annually). Patients with commercial insurance are candidates to receive Emgality for up to 12 months free of charge as part of Lilly’s patient support program (governmental beneficiaries excluded; subject to terms and conditions).

Source: Eli Lilly and Company, September 27, 2018

Generic Approvals

Carmustine for Palliative Cancer Care

Navinta LLC has received approval to market carmustine for injection USP, 100 mg/vial. This is the first generic version of BiCNU (Emcure Pharmaceuticals). Carmustine is used for palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in certain brain tumors, multiple myeloma, and relapsed or refractory Hodgkin’s lymphoma and non-Hodgkin’s lymphoma.

Source: FDA, September 11, 2018

Ticagrelor for Acute Coronary Syndrome

Watson Laboratories has received approval to market ticagrelor tablets, 60 mg and 90 mg, the first generic version of Brilinta (AstraZeneca). Ticagrelor is used in post-acute coronary management.

Source: FDA, September 4, 2018

Arsenic Trioxide Injection for Acute Promyelocytic Leukemia

The FDA has allowed Fresenius Kabi USA to market the first generic form of Cephalon’s arsenic trioxide injection (Trisenox), 10 mg/10 mL (1 mg/mL), in a single-dose vial. Arsenic trioxide is used for induction of remission and consolidation in certain patients with acute promyelocytic leukemia who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy.

Source: FDA, August 31, 2018

NEW INDICATIONS

Stiolto Respimat for COPD

The FDA has expanded the indication for tiotropium bromide/olodaterol inhalation spray (Stiolto Respimat, Boehringer Ingelheim) to include treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Previously, the Stiolto Respimat indication was for the treatment of airflow limitation in patients with COPD, including chronic bronchitis and emphysema. The revised language broadens the indication and illustrates that tiotropium bromide/olodaterol does more than improve airflow.

The FDA also approved new labeling for tiotropium bromide/olodaterol inhalation spray that includes data showing a meaningful reduction in COPD exacerbations driven by tiotropium. The updated label will include clinical trial data on tiotropium bromide (Spiriva Respimat) that shows a decrease in exacerbations, as well as data from the DYNAGITO trial, a 52-week study involving more than 7,800 COPD patients, comparing Stiolto Respimat to Spiriva Respimat in the reduction of COPD exacerbations.

Stiolto Respimat should not be used to treat asthma or sudden symptoms of COPD. As with other inhaled medicines, Stiolto Respimat can cause serious side effects, including sudden shortness of breath that may be life-threatening. The most common side effects are runny nose, cough, and back pain.

Source: Boehringer Ingelheim, October 11, 2018

Gardasil 9 to Age 45 for HPV-Related Cancers and Diseases

The FDA has approved an additional application for Gardasil 9 (human papillomavirus [HPV] 9-valent vaccine, recombinant; Merck & Co., Inc.) to include women and men 27 through 45 years of age. The vaccine helps prevent infections from certain HPV-related cancers and diseases that are caused by nine types of HPV.

The Centers for Disease Control and Prevention says that being vaccinated with Gardasil 9 before infection could prevent more than 90% of these cancers (31,200 cases each year) from developing. The FDA granted the Gardasil 9 application Priority Review designation.

Gardasil 9, approved in 2014, could previously be used in males and females 9 through 26 years of age. The nine types of HPV it covers include the four addressed by its forerunner, Gardasil, which received FDA approval in 2006 and is no longer distributed in the United States. The most common adverse reactions to Gardasil 9 include injection-site pain, swelling, redness, and headaches.

In a study involving 3,200 women aged 27 through 45 years, who were followed for approximately 3.5 years, Gardasil was 88% effective in preventing a combination of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. The effectiveness of the vaccine in men of the same age is inferred from the data from women and younger men and from immunogenicity data from a clinical trial involving 150 men aged 27 through 45 years who received a three-dose regimen of Gardasil over six months.

Source: FDA, October 5, 2018

Hemlibra for Hemophilia A Without Inhibitors

The FDA has approved emicizumabkxwh (Hemlibra, Genentech, Inc.) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients of any age with hemophilia A without factor VIII inhibitors. Hemlibra is now the only prophylactic treatment for people with hemophilia A with and without factor VIII inhibitors that can be administered subcutaneously and with multiple dosing options (once weekly, every two weeks, or every four weeks).

This approval is based on positive results from the phase 3 HAVEN 3 and HAVEN 4 studies. In HAVEN 3, adults and adolescents 12 years of age or older with hemophilia A without factor VIII inhibitors who received emicizumab prophylaxis once weekly or every two weeks experienced a 96% and 97% reduction in treated bleeds, respectively, compared to those who received no prophylaxis. In the HAVEN 4 study of adults and adolescents 12 years of age or older with hemophilia A with and without factor VIII inhibitors, receiving emicizumab prophylaxis every four weeks led to clinically meaningful control of bleeding.

Emicizumab was granted Breakthrough Therapy and Priority Review designations by the FDA for hemophilia A without factor VIII inhibitors. It was approved by the FDA in November 2017 for adults and children with hemophilia A with factor VIII inhibitors.

Source: Genentech, October 4, 2018

Kyprolis/Dexamethasone Dosing for Relapsed or Refractory Multiple Myeloma

The FDA has approved a once-weekly dosing option for carfilzomib (Kyprolis, Amgen Inc.) in combination with dexamethasone for patients with relapsed or refractory multiple myeloma.

The approval is based on the phase 3 ARROW trial, which demonstrated that carfilzomib administered once weekly at 70 mg/m2 with dexamethasone achieved superior progression-free survival (PFS) and overall response rates (ORR), with a comparable safety profile, versus twice-weekly carfilzomib administered at 27 mg/m2 in combination with dexamethasone. Carfilzomib is not approved for twice-weekly 27 mg/m2 administration in combination with dexamethasone alone.

ARROW included 478 patients with relapsed and refractory multiple myeloma who received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent. Among patients treated with the once-weekly carfilzomib/dexamethasone regimen versus the twice-weekly regimen, PFS was 11.2 months versus 7.6 months; ORR was 62.9% versus 40.8%; and complete responses or better were seen in 7.1% of patients versus 1.7% of patients, respectively.

Overall safety profiles and discontinuation rates due to adverse events were similar in the two arms. The most frequently reported treatment-emergent adverse events were anemia, diarrhea, fatigue, hypertension, insomnia, and pyrexia.

Source: Amgen, October 1, 2018

Fycompa at Age 4 for Partial-Onset Seizures

Perampanel CIII (Fycompa, Eisai Inc.) has received an expanded FDA indication as monotherapy and for adjunctive use in pediatric patients four years of age and older for the treatment of partial-onset seizures (POS) with or without secondarily generalized seizures. The approval includes both tablet and oral suspension formulations.

The approval is supported by efficacy extrapolated from three phase 3 studies of perampanel in adults with POS. Safety was evaluated in two studies in pediatric patients aged 4 to less than 12 years with epilepsy; adverse reactions in this population were similar to those in patients aged 12 and older.

Perampanel was initially approved for adjunctive use in POS in 2012, and was later approved as adjunctive therapy for primary generalized tonic-clonic seizures in patients with epilepsy who were 12 years of age and older, and then as monotherapy for POS with or without secondarily generalized seizures in patients with epilepsy aged 12 years and older.

Source: Eisai Inc., September 28, 2018

NEW FORMULATIONS

Xolair Prefilled Syringes for Allergic Asthma and Chronic Idiopathic Urticaria

The FDA has approved 75 mg/0.5 mL and 150 mg/1 mL single-dose prefilled syringes for omalizumab (Xolair, Genentech, Inc.) as an additional formulation for both allergic asthma and chronic idiopathic urticaria (CIU) indications. The new formulation is expected to be available in the U.S. by the end of 2018.

Omalizumab is currently available in a 150-mg, single-dose vial with lyophilized, sterile powder for reconstitution. The prefilled syringes eliminate the need for health-care providers to reconstitute omalizumab before administering it.

Omalizumab is approved for the treatment of moderate-to-severe, persistent allergic asthma in people six years of age or older whose asthma symptoms are not controlled by inhaled corticosteroids, and for CIU in people 12 years of age and older who continue to have hives that are not controlled by H1 antihistamines.

Source: Genentech, September 28, 2018

Benzalkonium-Free Xelpros for Reduction of Elevated Intraocular Pressure

The FDA has approved latanoprost ophthalmic emulsion, 0.005% (Xelpros, Sun Pharmaceutical Industries Ltd.) for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. This is the first form of latanoprost that is not formulated with benzalkonium chloride, a preservative commonly used in topical ocular preparations.

In randomized, controlled clinical trials of patients with open-angle glaucoma or ocular hypertension with a mean baseline IOP of 23–26 mmHg, latanoprost lowered IOP by a mean of up to 6–8 mmHg.

Xelpros was developed using Sun Pharmaceutical’s proprietary swollen micelle microemulsion technology.

Source: Sun Pharmaceutical Industries Limited, September 14, 2018

Subcutaneous Actemra for Active Systemic Juvenile Idiopathic Arthritis

The FDA has approved the subcutaneous formulation of tocilizumab (Actemra, Genentech, Inc.) for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients two years of age and older. Tocilizumab can be given alone or in combination with methotrexate in patients with SJIA. In 2011, the FDA approved the intravenous formulation of tocilizumab for patients aged two and older with active SJIA.

The tocilizumab subcutaneous formulation comes in a prefilled syringe that can be injected at home.

The approval is based on data from JIGSAW-118, a 52-week, open-label, multicenter, phase 1b pharmacokinetic/pharmacodynamic bridging study designed to determine the appropriate dosing regimen of subcutaneous tocilizumab across a range of body weights in children with SJIA.

Source: Genentech, September 13, 2018

New Dosage of Buprenorphine and Naloxone Sublingual Film for Maintenance Treatment of Opioid Dependence

The FDA has approved a new version of buprenorphine and naloxone sublingual film (Cassipa, Teva Pharmaceuticals USA, Inc.) for the maintenance treatment of opioid dependence. This provides a new dosage strength (16 mg/4 mg) of buprenorphine and naloxone sublingual film, which is also approved in both brand-name and generic versions and in various strengths.

Cassipa was approved through the (abbreviated) 505(b)(2) pathway based on an application that relied, in part, on the FDA’s finding of safety and effectiveness for Suboxone sublingual film (Indivior) to support approval. The application demonstrated that reliance on the FDA’s finding of safety and effectiveness for Suboxone was scientifically justified and provided Cassipa-specific pharmacokinetic data to establish the drug’s safety and efficacy for its approved uses.

Cassipa should be used as part of a complete treatment plan that includes counseling and psychosocial support and should only be used after patient induction and stabilization up to a dose of 16 mg of buprenorphine using another marketed product. Adverse events commonly observed with the buprenorphine and naloxone sublingual film are oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema. These products may only be prescribed by Drug Addiction Treatment Act-certified prescribers.

Source: FDA, September 7, 2018

FDA ACTIONS

Breakthrough Therapy Status

JAK3 Inhibitor for Alopecia Areata

The FDA has granted Pfizer, Inc., Breakthrough Therapy designation for the oral Janus kinase 3 (JAK3) inhibitor PF-06651600 for alopecia areata.

There are no FDA-approved treatments for alopecia areata, in which immune cells attack healthy hair follicles, causing the hair to fall out. The mean age of onset is between 25 and 35, but it can also affect children and adolescents. It is seen in both sexes and all ethnicities. More than half of patients experience poor health-related quality of life and the condition may lead to serious psychological consequences.

The JAK pathways are believed to play an important role in inflammatory processes. PF-06651600 is an oral small molecule that selectively inhibits JAK3. The drug is also under investigation for the treatment of rheumatoid arthritis, Crohn’s disease, and ulcerative colitis.

Source: Pfizer, September 5, 2018

CA-008 for Postsurgical Pain

The FDA has granted Breakthrough Therapy designation to CA-008 (Concentric Analgesics, Inc.) for postsurgical pain. CA-008 is a first-in-class non-opioid therapeutic that rapidly converts to capsaicin, a potent TRPV1-agonist. It provides long-lasting pain relief after a single local injection by selectively desensitizing pain-conducting nerve fibers, without producing numbness or weakness. The compound is designed to provide clinically meaningful pain relief for a week or more, significantly reducing or eliminating the need for opioids in the postoperative period.

In a phase 1b placebo-controlled clinical trial in patients undergoing bunionectomy, CA-008, at the highest dose, showed a 63% reduction of pain intensity compared with placebo. The study also showed pain reductions with CA-008 at 48, 72, 96, and 120 hours. Opioid consumption in patients taking CA-008 fell by nearly 50% compared to those taking placebo. CA-008 was safe and well tolerated at all doses.

Source: Concentric Analgesics, September 11, 2018

PF-06482077 for Invasive Disease and Pneumonia

Pfizer, Inc., has received Breakthrough Therapy designation for its 20-valent pneumococcal conjugate vaccine candidate, PF-06482077, designed to prevent invasive disease and pneumonia caused by Streptococcus pneumoniae serotypes in adults aged 18 years and older.

The designation is based on phase 2 trial results in adults aged 60 through 64 years. Pfizer expects to start phase 3 trials in a few months.

Source: Pfizer, September 20, 2018

Tezepelumab for Severe Asthma

Amgen Inc., and AstraZeneca have received Breakthrough Therapy designation for tezepelumab in patients with severe asthma without an eosinophilic phenotype.

Multiple inflammatory pathways are involved in asthma. More than two-thirds of patients with severe asthma have type 2 (T2) inflammation-driven asthma, which includes the eosinophilic phenotype, typically characterized by elevated levels of T2 inflammatory biomarkers.

Tezepelumab is a potential first-in-class drug that blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine critical to airway inflammation. Blocking TSLP may prevent immune cells from releasing proinflammatory cytokines. Due to its activity early in the inflammation cascade, tezepelumab may be suitable for a broad population of patients with severe, uncontrolled asthma, irrespective of patient phenotype.

In a phase 2b trial (PATHWAY), tezepelumab significantly reduced the annual asthma exacerbation rate compared with placebo in a range of severe asthma patients, independent of baseline blood eosinophil count or other T2 inflammatory biomarkers. Tezepelumab is now in the phase 3 PATHFINDER clinical trial program.

Source: Amgen and AstraZeneca, September 6, 2018

Priority Review Status

Keytruda for NSCLC

The FDA has granted Priority Review status to a supplemental biologics-license application for pembrolizumab (Keytruda, Merck & Co, Inc.), as monotherapy for first-line treatment of locally advanced or metastatic nonsquamous or squamous non–small-cell lung cancer (NSCLC) in patients whose tumors express programmed death ligand-1 (tumor proportion score [TPS] of at least 1%) without EGFR or ALK genomic-tumor aberrations.

The application is based on data from the phase 3 KEYNOTE-042 trial, one of five phase 3 trials with pembrolizumab in NSCLC to demonstrate a significant improvement in overall survival.

The FDA has set a Prescription Drug User Fee Act date of January 11, 2019.

Source: Merck, September 12, 2018

Keytruda for Merkel Cell Carcinoma

The FDA has granted Priority Review status for a new, supplemental biologics-license application seeking accelerated approval for pembrolizumab (Keytruda, Merck & Co, Inc.) for the treatment of adult and pediatric patients who have recurrent, locally advanced, or metastatic Merkel cell carcinoma (MCC).

MCC is an aggressive, rare form of skin cancer that is often caused by a Merkel cell-associated polyomavirus. It is estimated that about 2,500 cases of MCC are diagnosed each year in the U.S. MCC has an 18-month survival rate of about 30%.

The application is based on data from the phase 2 KEYNOTE-017 trial involving patients with advanced MCC, which has demonstrated durable tumor control in these patients. The FDA has set a target action date of December 28, 2018.

Source: Merck, September 4, 2018

Fast Track Designations

CX-01 for Acute Myeloid Leukemia

Cantex Pharmaceuticals, Inc., has been granted Fast Track designation for CX-01 for the treatment of patients older than 60 years of age who are receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).

AML is the most common form of acute leukemia in adults. More than 60% of patients are older than 60; their response to initial induction therapy is lower, their risk of relapse is higher, and their overall survival rate is generally lower.

CX-01 is designed to block the activity of chemokines (including CXCR4, CXCL12, and platelet factor 4) that support the resistance of blood cancers to treatment and contribute to the delay of bone marrow recovery after chemotherapy.

Source: Cantex Pharmaceuticals, August 27, 2018

Miransertib for PIK3CA-Related Overgrowth Spectrum

The FDA has granted Fast Track designation to miransertib (ARQ 092, ArQule, Inc.) for the treatment of PIK3CA-related overgrowth spectrum (PROS), a group of genetic disorders characterized by excessive tissue growth.

While diseases in the overgrowth spectrum have similar symptoms, each is defined by unique clinical characteristics. Genetic sequencing has identified the genetic mutations that drive these disorders, permitting the development of medicines that target specific causes. Proteus syndrome, a PROS disorder, is an ultrarare condition characterized by the aberrant overgrowth of multiple body tissues. There are no approved medicinal treatments, and the mortality rate is 25% by the age of 22.

Miransertib is an orally available, selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2, and 3 isoforms. Dysregulation of AKT has been implicated in a variety of rare overgrowth diseases and cancers. AKT inhibitors show significant promise in molecularly defined patient populations.

Miransertib is in a phase 1/2 study for PROS, a phase 1 study for Proteus syndrome, and a phase 1b study in combination with anastrozole in patients with advanced endometrial cancer with AKT and PI3K mutations.

Source: ArQule, September 13, 2018

Praliciguat for Heart Failure

Ironwood Pharmaceuticals, Inc., has been granted Fast Track designation for praliciguat (IW-1973) for the treatment of patients with heart failure with preserved ejection fraction (HFpEF).

In HFpEF, the left ventricle becomes stiff, meaning the heart can’t fill sufficiently with blood. HfpEF is characterized by exercise intolerance, frequent hospitalizations, and increased risk of death. The number of people with HFpEF is rising.

Praliciguat, an investigational, orally administered, soluble guanylate cyclase-stimulator, improves tissue blood flow and reduces cardiac vascular inflammation and fibrosis. It enhances nitric oxide signaling, which may improve vascular and metabolic function and decrease the inflammatory and fibrotic consequences associated with these diseases.

Praliciguat is in phase 2 clinical trials involving patients with diabetic nephropathy and patients with HFpEF.

Source: Ironwood Pharmaceuticals, September 13, 2018

Contezolid and Contezolid Acefosamil for Skin Infections

MicuRx Pharmaceuticals, Inc., has received Fast Track designation and Qualified Infectious Disease Product classification for contezolid (MRX-I) and its prodrug contezolid acefosamil (MRX-4) for the treatment of acute bacterial skin and skin structure infections (ABSSSI).

Very few oral agents are available for serious infections with methicillin-resistant Staphylococcus aureus (MRSA). Moreover, transitioning patients with serious infections from the hospital to oral outpatient treatment as soon as possible is more convenient and cost-effective than continued hospitalization or outpatient IV treatment.

Contezolid and contezolid acefosamil are next-generation oxazolidinone agents. Compared with earlier antibiotics in this class, they have reduced hematologic toxicity while maintaining excellent therapeutic efficacy. Contezolid and contezolid acefosamil are active against multidrug-resistant, gram-positive organisms, including MRSA and vancomycin-resistant Enterococci.

Source: MicuRx Pharmaceuticals, September 21, 2018

Orphan Drug Designations

OBI-3424 for Acute Lymphoblastic Leukemia

The FDA has granted Orphan Drug designation for OBI-3424 (OBI Pharma, Inc.) for the treatment of acute lymphoblastic leukemia (ALL).

ALL, a rare blood cancer affecting the maturation of B-cell and T-cell lymphoblasts from progenitor cells, primarily affects children. The remission rate for pediatric ALL is approximately 90%, with overall survival around 60% to 70%. However, current treatments for ALL have been less successful in infants, adults, and patients with recurrent disease.

AKR1C3 overexpression has been documented in difficult-to-treat cancers, including ALL. OBI-3424 is a first-in-class, small-molecule prodrug that targets cancers overexpressing AKR1C3 and selectively releases a potent DNA-alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents such as cyclophosphamide and ifosfamide, which are nonselective.

Source: OBI Pharma, September 19, 2018

ARM210/S48168 for Certain Myopathies

ARMGO Pharma, Inc., has been granted Orphan Drug designation for ARM210 (also known as S48168), a potential treatment for patients with ryanodine receptor 1-related myopathies (RYR1-RM). In 2015, the FDA granted Orphan Drug and Rare Pediatric Disease designations to ARM210 as a potential treatment for Duchenne muscular dystrophy (DMD).

ARM210 targets the ryanodine receptor calcium-release channel, an intracellular channel that becomes leaky in several diseases, including DMD and RYR1-RM. The leaks impair muscle contraction and activate toxic pathways that damage muscle. RYR1-RM comprises a group of rare skeletal muscle diseases due to mutations in the RYR1 gene, which lead to leaky channels. RM210 binds to those channels and repairs the leaks.

Source: ARMGO Pharma, September 5, 2018

SYNT001 for Pemphigus

The FDA has granted Orphan Drug designation to SYNT001 (Syntimmune, Inc.) for the treatment of pemphigus, a severe autoimmune disease that leads to painful blistering.

SYNT001 is an investigational, humanized immunoglobulin G (IgG)-4 monoclonal antibody optimized to inhibit FcRn binding to IgG at both neutral and acidic pH. Positive preliminary results from a phase 1b trial showed that SYNT001 appeared to be well tolerated and induced a rapid reduction in IgG and IgG-circulating immune complex levels. SYNT001 also promoted clinical improvement as measured by Pemphigus Disease Area Index score, with the clinical effect persisting beyond the treatment period.

Source: Syntimmune, September 12, 2018

ATI-1013 for Buerger’s Disease

Antidote Therapeutics, Inc., has been granted Orphan Drug designation for ATI-1013, a fully human, anti-nicotine monoclonal antibody for the treatment of Buerger’s disease (thromboangitis obliteransin).

In Buerger’s disease, small blood vessels in the arms, legs, or both become blocked, causing pain, skin ulcers, and eventually severe tissue damage that often leads to gangrene and amputation. Buerger’s disease is caused by smoking cigarettes or ingesting nicotine from other sources (such as smokeless tobacco); it largely affects young or middle-aged cigarette smokers. Since many patients are unable to stop using tobacco, a human monoclonal antibody that blocks the effects of nicotine may be a major advance.

ATI-1013 is a proprietary compound that neutralizes nicotine in the blood. Studies in animals have shown that following an injection of nicotine, ATI-1013 blocks nicotine-induced increases in blood pressure, reduces nicotine levels in the brain by more than 90%, and reduces the vasoconstrictive peripheral effects of nicotine on blood vessels.

Source: Antidote Therapeutics, September 5, 2018

Label Update

New Dosing for Ixiaro

The FDA has approved an accelerated dosing regimen for Japanese encephalitis vaccine, inactivated, adsorbed (Ixiaro, Valneva USA, Inc.), the only vaccine approved in the U.S. indicated for protection against disease caused by the Japanese encephalitis virus.

For effective protection, adults 18 to 65 years of age may now receive two separate doses of Ixiaro seven days apart. Previously, the time between doses for this age group was 28 days. The standard 28-day schedule still applies to children aged 2 months to 17 years and adults 66 years and older; adults 18 to 65 years of age may also follow this schedule. Dosing must be completed at least seven days before travel to endemic areas.

Source: Valneva USA, October 5, 2018

DRUG SAFETY ISSUES

New REMS for Opioids

The FDA has approved a final Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) that includes measures to help better communicate the serious risks about the use of opioid pain medications to patients and healthcare professionals. This expanded REMS now applies to immediate-release (IR) opioid analgesics intended for use in an outpatient setting. The new REMS also applies to the extended-release and long-acting (ER/LA) opioid analgesics, which have been subject to a REMS since 2012.

For the first time, the REMS program requires training to be available to health-care providers (e.g., nurses and pharmacists) who are involved in the management of patients with pain, and not only to prescribers. The new REMS also requires that the education cover broader information about appropriate pain management, including alternatives to opioids for the treatment of pain. The FDA is also approving new product labeling that contains information about the health-care provider education available through the new REMS.

Since 2012, manufacturers of ER/LA opioid analgesics have been subject to a REMS requiring that training be made available to prescribers of those products. However, the IR drugs account for about 90% of all opioid pain medications prescribed for outpatient use. The entire class of transmucosal immediate-release fentanyl prescription medicines has been subject to a REMS since December 2011.

The ER/LA Opioid Analgesic REMS previously included 62 products, but the modified Opioid Analgesic REMS requires that 347 opioid analgesics intended for outpatient use be subject to these REMS requirements.

There is no mandatory federal requirement that prescribers or other health-care providers take the training provided through the REMS, and completion of the training is not a precondition to prescribing opioid analgesics to patients. However, the FDA’s Opioid Policy Steering Committee continues to consider whether there are circumstances when the FDA should require some form of mandatory education for health-care providers and how the agency would pursue such a goal.

Source: FDA, September 18, 2018

FDA Review Finds No New Risks for Nuplazid

The FDA has completed a review of all post-marketing reports of deaths and serious adverse events reported with the use of pimavanserin (Nuplazid, Acadia Pharmaceuticals, Inc.). Based on an analysis of all available data, the agency did not identify any new or unexpected safety findings or findings that are inconsistent with the established safety profile described in the drug label. After a thorough review, the FDA’s conclusion remains unchanged: the drug’s benefits outweigh its risks for patients with hallucinations and delusions associated with Parkinson’s disease psychosis.

Pimavanserin and other antipsychotics have a boxed warning regarding the increased risk of death in elderly patients with dementia-related psychosis associated with the use of these drugs.

The FDA did observe some prescribing patterns of potential concern, such as the concomitant use of other antipsychotic drugs or drugs that can cause QT prolongation. The risk of QT prolongation and serious arrhythmia associated with Nuplazid are noted in the prescribing information. The FDA reminds healthcare providers to be aware of these risks.

Source: FDA, September 20, 2018

Second Impurity in Recalled Valsartan

The FDA has discovered a new impurity in three lots of Torrent Pharmaceuticals’ valsartan products that were included in the company’s recall on August 23, 2018. This second impurity, N-Nitrosodiethylamine (NDEA), is a known suspected carcinogen.

The FDA and the European Medicines Agency have learned that Zhejiang Huahai Pharmaceuticals (ZHP) found NDEA in several batches of its drug containing valsartan as the active pharmaceutical ingredient (API). The FDA immediately began retesting all valsartan API and products for NDEA, including both recalled products and those currently marketed in the U.S., and has discovered NDEA in some of ZHP’s valsartan API. This impurity was also found in Torrent’s valsartan 160-mg (lot BV47D001) and 320-mg (lots BV48D001 and BV48D002) tablets, which were made using valsartan API from ZHP and were part of the earlier recall. The testing shows also that not all products made using ZHP’s valsartan API contain the NDEA impurity.

The FDA will update the list of products included (and those not included) in the recall as more information becomes available.

Source: FDA, September 13, 2018

Foster Children and Psychiatric Drugs

Powerful psychiatric drugs are potentially being prescribed to thousands of foster children without basic safeguards, according to a report released by the Department of Health and Human Services (HHS) inspector general. The report found that close to one in three foster children from a sample of states were prescribed psychiatric drugs without treatment plans or follow-up, which are standard steps in good medical care.

Foster children are much more likely to receive psychiatric drugs than children overall. However, investigators also said that children who need medication to help them function at school and in social settings may be going untreated.

The inspector general is recommending that the HHS Administration for Children and Families develop a strategy to help states meet their current requirements for prescribing psychiatric drugs to foster children, and to generally raise standards for case-by-case oversight. Medicaid spends hundreds of millions of dollars annually on psychiatric drugs, and estimates suggest that 120,000 children in foster care take at least one psychiatric medication.

Source: STAT, September 17, 2018

DEVICE AND DIAGNOSTIC APPROVALS

Bose Hearing Aid

The FDA has allowed marketing of the Bose Hearing Aid (Bose Corporation), which is intended to amplify sounds for individuals aged 18 or older with perceived mild-to-moderate hearing impairment. The Bose Hearing Aid is the first aid to receive FDA authorization for marketing that will enable users to fit, program, and control the aid on their own, without assistance from a healthcare provider.

Approximately 37.5 million adults 18 years of age and older report having some trouble hearing without a hearing aid.

The Bose Hearing Aid is a user-fitted, wireless, air-conduction hearing aid. Air-conduction hearing aids work by capturing sound vibrations through one or more microphones. The signal is processed, amplified, and played back through an earphone placed in the ear canal. Patients can adjust the hearing aid through a mobile application on their phone. This technology enables users to fit the hearing aid settings themselves, in real-time and in real-world environments, without the assistance of a healthcare professional.

While users may fit, program, and control the Bose Hearing Aid on their own, the device must comply with applicable federal and state laws regarding the sale of hearing aids, including state laws that might require hearing aids to be purchased from or dispensed by a licensed hearing-aid dispenser. The FDA is drafting proposed regulations for a new category of over-the-counter hearing aids as required by the FDA Reauthorization Act of 2017.

In authorizing marketing of the Bose device, the FDA reviewed data from clinical studies of 125 patients, which demonstrated that outcomes with self-fitting of the Bose Hearing Aid are comparable on average to those with professional fitting of the same device with respect to the amount of amplification selected, speech in noise testing, and overall benefit. In addition, when participants self-fit the Bose Hearing Aid, they generally preferred those hearing- aid settings over the professionally selected settings.

The Bose Hearing Aid was reviewed under the FDA’s de novo premarket review pathway.

Source: FDA, October 8, 2018

Artery Perforation Treatment

The FDA has approved a device to treat acute coronary artery perforations that can occur during percutaneous coronary intervention (PCI) procedures. The PK Papyrus Covered Coronary Stent System (Biotronik) is the first device approved for this indication in 17 years.

The PK Papyrus stent system is a balloon-expandable, covered coronary stent and delivery system. It is advanced into the perforated coronary artery using a balloon catheter. Once the PK Papyrus stent is implanted, it provides a physical barrier to seal the tear in the artery wall while still allowing blood to flow through the device to the heart muscle. Successful sealing of a coronary perforation with the device can be a life-saving procedure, obviating the need for open-heart surgery.

The FDA reviewed real-world survey data from 80 patients who received PK Papyrus stents to treat coronary artery perforations. Stents were successfully delivered to the perforation site in 95% of patients, and the device successfully sealed the perforation in 73 patients (91.3%). Two deaths occurred during PCI, and seven patients underwent treatment to drain fluid collection around the heart. Post-procedure, in-hospital death occurred in five patients with perforations successfully sealed by PK Papyrus stents and in one patient for whom the PK Papyrus stent did not successfully seal the perforation.

The PK Papyrus system, reviewed under the humanitarian device exemption process, is contraindicated for patients who are not considered candidates for standard PCI procedures and patients with a known allergy or hypersensitivity to amorphous silicon carbide or any other compound of the product.

Source: FDA, September 14, 2018

ClonoSEQ Assay for Minimal Residue Disease with Acute Lymphoblastic Leukemia or Multiple Myeloma

The FDA has permitted marketing of the ClonoSEQ assay (Adaptive Biotechnologies Corporation), a next generation sequencing (NGS)-based test for minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) or multiple myeloma (MM).

MRD, which measures the number of cancer cells remaining in bone marrow during or after treatment, is useful in evaluating patients who have responded to therapy when their tumor burden is below what can be detected with standard methods. Detection of MRD is associated with recurrence of the disease. Currently, providers test for MRD using flow cytometry assays or polymerase chain reaction (PCR)-based assays that are usually capable of measuring MRD down to one in 10,000 or one in 100,000 cells. ClonoSEQ can detect MRD at levels below one in one million cells.

The ClonoSEQ assay, an in vitro diagnostic, uses multiplex PCR and NGS to identify and quantify certain gene sequences in DNA extracted from bone marrow from patients with ALL or MM. The provider collects the single-site assay and sends it to Adaptive Biotechnologies for evaluation.

The FDA evaluated data to demonstrate clinical validity from a retrospective analysis of samples obtained from three previously conducted clinical studies. These included 273 patients with ALL, an ongoing study of 323 patients with MM, and a study of 706 patients with MM. The FDA reviewed the ClonoSEQ assay through the de novo premarket review pathway.

Source: FDA, September 28, 2018

Recell for Severe Burns

The FDA has approved marketing of the Recell Autologous Cell Harvesting Device (Avita Medical Ltd.) to treat severe thermal burns in patients 18 years of age and older.

The Recell System uses a small amount of a patient’s skin to prepare Spray-On Skin Cells at the point of care in as little as 30 minutes. Two randomized, controlled clinical trials demonstrated that treatment of acute burn wounds with the Recell System required substantially less donor skin than that required with conventional split-thickness autografts to achieve closure of burn wounds.

Source: Avita Medical, September 20, 2018

BioCode GI Panel for 17 Causes of Infectious Diarrhea

The BioCode Gastrointestinal Pathogen Panel with high throughput BioCode MDx-3000 molecular system (Applied BioCode, Inc.) has received FDA 510(k) clearance. The panel tests for 17 common bacteria, viruses, and parasites that cause infectious diarrhea. Clearance was granted based on a successful clinical study that included more than 1,558 prospective samples, archived positives, and contrived samples.

The system is designed for mediumto high-volume molecular testing in large hospitals and reference laboratories. It automates the PCR amplification, hybridization/target capture, and detection steps of molecular diagnostic testing.

Source: Applied BioCode, October 1, 2018

Therascreen for Non–Small-Cell Lung Cancer

Therascreen EGFR RGQ PCR Kit (Qiagen N.V.) received FDA approval as a companion diagnostic with dacomitinib (Vizimpro, Pfizer, Inc.) in first-line treatment of patients with non–small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutation. Therascreen is now approved as a companion diagnostic to guide the use of three FDA-approved therapies, including afatinib (Gilotrif, Boehringer Ingelheim) and gefitinib (Iressa, AstraZeneca).

Source: Qiagen, September 28, 2018

Altapore for Spine Surgery

Altapore Bioactive Bone Graft (Baxter International, Inc.) has received FDA clearance for use as an autograft extender in posterolateral spinal fusion. Altapore had previously been cleared for use in orthopedic surgical procedures in the extremities and pelvis.

Altapore is designed to enhance bone growth with optimized porosity that promotes earlier vascularization, which plays a central role in the bone formation process by providing oxygen, nutrients, and growth factors critical for bone development.

Source: Baxter International, September 26, 2018

DEVICE RECALL

Endologix Extends Recall to All AFX Endovascular AAA Systems

Endologix is recalling its AFX endovascular abdominal aortic aneurysm (AAA) systems after continued reports of Type IIIa and IIIb endoleaks, which increase the likelihood of aorta rupture or death if left untreated or not detected.

While the class 1 recall applies to all AFX Endovascular AAA Systems, the AFX with Strata graft material is the source of most reports of endoleaks. Endologix has not manufactured this model since July 2014 and health-care providers were advised to remove any remaining inventory in December 2016.

AFX with Duraply graft material and AFX2 devices have only been distributed for a short period, and it is unclear if they have fewer endoleaks or have not been used for long enough for endoleaks to occur.

The new recall updates the December 2016 notification and informs physicians about new patient surveillance recommendations and general warnings on interventions to or through existing AFX devices.

Source: FDA, October 17, 2018