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P T. 2018;43(1): 13-21, 28-30

Drug and Device News January 2018


Sublocade, a Once-Monthly Buprenorphine Injection

The FDA has approved Sublocade (Indivior, Inc.), the first once-monthly buprenorphine injection for the treatment of moderate-to-severe opioid use disorder (OUD) in adults who have initiated treatment with a transmucosal buprenorphine-containing product. It is indicated for patients who have been on a stable dose of buprenorphine treatment for at least seven days.

Buprenorphine for OUD treatment is currently approved to administer as a tablet or film that dissolves in the mouth or as an implant.

Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support. It is a drug–device combination product that utilizes buprenorphine and the Atrigel delivery system in a prefilled syringe. It is injected subcutaneously by a health care professional as a solution and forms a solid deposit, or depot, containing buprenorphine. Buprenorphine is released by the biodegradation of the depot. In clinical trials, Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval.

The safety and efficacy of Sublocade were evaluated in two clinical trials of 848 adults with a diagnosis of moderate-to-severe OUD who began treatment with buprenorphine/naloxone sublingual film. Once the dose was determined stable, patients were given Sublocade by injection. Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared with the placebo group.

The FDA is requiring post-marketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer interdose interval than once monthly, and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment.

Sublocade has a boxed warning that includes the risks of intravenous self-administration. If the product is administered intravenously, the solid mass could cause occlusion, tissue damage, or embolus. Sublocade must be prescribed and dispensed under a risk evaluation and mitigation strategy.

Source: FDA, November 30, 2017

Juluca for HIV

The FDA has approved the first complete regimen containing only two drugs to treat human immunodeficiency virus type 1 (HIV-1) instead of the three or more drugs in standard HIV therapies. Juluca (dolutegravir 50 mg/rilpivirine 25 mg, ViiV Healthcare) is a fixed-dose tablet indicated for adults whose virus is suppressed on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the new tablet’s individual components.

Dolutegravir (ViiV Healthcare) is an integrase strand transfer inhibitor, and rilpivirine (Janssen Therapeutics) is a non-nucleoside reverse transcriptase inhibitor.

This approval is based primarily on data from the phase 3 trials SWORD-1 and SWORD-2, which showed the two-drug regimen achieved noninferior viral suppression (HIV-1 RNA less than 50 copies per mL) at 48 weeks compared with patients’ three- or four-drug current antiretroviral regimen in both pooled and individual analyses of the two studies. Virological suppression rates were similar between treatment arms.

Drug-related adverse events and adverse events leading to withdrawal occurred at low frequencies in both arms of the study, but more frequently in the investigational arm. The most common side effects in patients taking Juluca were diarrhea and headache.

Limiting the number of drugs in an HIV treatment regimen can help reduce toxicity for patients.

Sources: FDA and ViiV Healthcare, November 21, 2017

Hemlibra for Hemophilia A With Inhibitors

Emicizumab-kxwh (Hemlibra, Genentech) has received FDA approval for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors—the first new medication for these patients in almost 20 years. Nearly one in three people with severe hemophilia A can develop inhibitors to factor VIII replacement therapies.

In the phase 3 HAVEN 1 study, people 12 years of age or older with hemophilia A with inhibitors who received emicizumab-kxwh prophylaxis had a statistically significant reduction in treated bleeds of 87% compared with those who received no prophylaxis. Interim results from the pivotal HAVEN 2 study in children younger than 12 years of age with hemophilia A with inhibitors showed that 87% who received emicizumab-kxwh prophylaxis experienced zero treated bleeds.

The most common adverse events occurring in 10% or more of people treated with emicizumab-kxwh in pooled studies were injection-site reactions, headache, and arthralgia.

Emicizumab-kxwh is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for hemophilia A patients. Emicizumab-kxwh can be administered by an injection of a ready-to-use solution subcutaneously once weekly. Emicizumab-kxwh was created by Chugai Pharmaceutical Co., Ltd., and is being codeveloped by Chugai, Genentech, and Roche (Genentech’s parent company).

Source: Genentech, November 16, 2017

Fasenra for Asthma

Benralizumab (Fasenra, AstraZeneca/MedImmune) has won FDA approval as an add-on maintenance treatment for patients 12 years of age and older who have severe asthma with an eosinophilic phenotype.

The approval is based on the phase 3 SIROCCO, CALIMA, and ZONDA trials. Results for the eight-week benralizumab dosing regimen from these trials showed a reduction of up to 51% in the annual asthma exacerbation rate versus placebo; improvement in lung function as measured by forced expiratory volume in one second of up to 159 mL versus placebo; and a 75% median reduction in daily oral corticosteroid use.

Benralizumab provides direct, rapid, and near-complete depletion of eosinophils within 24 hours. Eosinophils are a type of white blood cell that are a normal part of the body’s immune system. Elevated levels of eosinophils, seen in about half of severe asthma patients, impact airway inflammation and airway hyper-responsiveness, resulting in increased asthma severity and symptoms, decreased lung function, and increased risk of exacerbations.

Benralizumab is a monoclonal antibody that binds directly to the interleukin-5–alpha receptor on an eosinophil and attracts natural killer cells to induce apoptosis. It will be available as a subcutaneous injection via a prefilled syringe administered once every four weeks for the first three doses, and then once every eight weeks thereafter.

Source: AstraZeneca/MedImmune, November 15, 2017

Abilify With Tracking Sensor

The FDA has approved aripiprazole tablets with a sensor (Abilify MyCite, Otsuka Pharmaceutical Co., Ltd.), the first U.S. drug with an ingestible sensor embedded in the pill that records that the medication was taken. The product is approved for the treatment of schizophrenia, for acute treatment of manic and mixed episodes associated with bipolar I disorder, and for use as an add-on treatment for adult depression.

The pill’s sensor sends a message to a wearable patch, which transmits the information to a mobile application so that patients can track the ingestion of the medication on their smart phone. Patients can permit their caregivers and physician to access the information through a Web portal. The product’s ability to improve patient compliance with treatment has not been shown. Abilify MyCite should not be used to track drug ingestion in “real time” or during an emergency because detection may be delayed or may not occur.

Abilify MyCite includes a boxed warning that elderly patients with dementia-related psychosis treated with anti-psychotic drugs are at an increased risk of death. Abilify MyCite is not approved to treat patients with dementia-related psychosis. The boxed warning also cites an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. The safety and effectiveness of Abilify MyCite have not been established in pediatric patients. Abilify MyCite must be dispensed with a patient medication guide.

Prior to initial patient use of the product, the patient’s health care professional should facilitate use of the drug, patch, and app to ensure the patient is capable and willing to use the system.

Skin irritation may occur at the site of the MyCite patch placement in some patients.

The FDA approved Abilify to treat schizophrenia in 2002 and first permitted marketing of the ingestible sensor in 2012. The sensor technology and patch are made by Proteus Digital Health.

Source: FDA, November 13, 2017

Heplisav-B HBV Vaccine

Heplisav-B (hepatitis B vaccine, recombinant [adjuvanted], Dynavax Technologies Corp.) has received FDA approval for prevention of infection caused by all known subtypes of hepatitis B virus (HBV) in adults 18 years of age and older. Heplisav-B is the first new HBV vaccine in the U.S. in more than 25 years and the only two-dose HBV vaccine for adults.

In 2015, new cases of extremely infectious acute HBV increased by more than 20% nationally. HBV can be prevented through effective vaccination. Current vaccines require three shots over six months, but almost half of adults fail to complete the series within one year.

Heplisav-B combines hepatitis B surface antigen with Dynavax’s proprietary Toll-like receptor 9 agonist to enhance the immune response. The vaccine’s approval was based on data from three phase 3 noninferiority trials of nearly 10,000 adults who received Heplisav-B. The pivotal studies compared Heplisav-B administered in two doses over one month with Engerix-B (GlaxoSmithKline) administered in three doses over six months.

In the largest phase 3 trial, Heplisav-B demonstrated a statistically significantly higher rate of protection of 95% compared with 81% for Engerix-B. Across the three trials, the most common local reaction was injection-site pain, while the most common systemic reactions were fatigue and headache.

Dynavax expects to launch Heplisav-B in the United States in the first quarter of 2018.

The Centers for Disease Control and Prevention recommends HBV vaccination for those at high risk for infection due to their jobs, lifestyle, living situations, and travel to certain areas.

Source: Dynavax, November 9, 2017

Prevymis for CMV Prevention

The FDA has approved letermovir (Prevymis, Merck) for the prevention of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT). The medication will be available as once-daily tablets for oral use and as an injection for intravenous infusion.

Letermovir is the first new U.S. medicine approved in 15 years for CMV infection, a common and potentially serious infection in allogeneic HSCT recipients. CMV-seropositive patients who undergo an HSCT are at high risk for CMV reactivation. Any level of CMV infection is associated with increased mortality in HSCT patients.

In the pivotal phase 3 clinical trial supporting approval, significantly fewer patients in the letermovir group (38%) compared with the placebo group (61%) developed clinically significant CMV infection, discontinued treatment, or had missing data through week 24 post-HSCT. All-cause mortality in patients receiving letermovir was lower compared with placebo—12% versus 17%, respectively—at week 24 post-transplant.

In trials, the cardiac adverse event rate (regardless of investigator-assessed causality) was higher in patients receiving letermovir than placebo (13% versus 6%). The most common cardiac adverse events were tachycardia and atrial fibrillation, reported as mild or moderate. The adverse events occurring in at least 10% of letermovir-treated HSCT recipients and at a frequency at least 2% greater than placebo were nausea, diarrhea, vomiting, peripheral edema, cough, headache, fatigue, and abdominal pain.

Sources: Merck, November 9, 2017, and FDA, November 8, 2017

Mepsevii for MPS VII

Vestronidase alfa-vjbk (Mepsevii, Ultragenyx Pharmaceutical, Inc.), the first treatment for children and adults with mucopolysaccharidosis type VII (MPS VII), has received FDA approval. MPS VII, also known as Sly syndrome, is an inherited metabolic condition that affects fewer than 150 patients worldwide.

Features of MPS VII vary widely, but most patients have skeletal abnormalities that become more pronounced with age. Patients can also develop heart valve abnormalities, enlarged liver and spleen, and narrowed airways that can lead to lung infections and trouble breathing. Some affected individuals do not survive infancy, while others live into adolescence or adulthood.

MPS VII is a lysosomal storage disorder caused by deficiency of the enzyme beta-glucuronidase, which causes an abnormal buildup of toxic materials in the cells. Vestronidase alfa-vjbk is an enzyme replacement therapy.

The safety and efficacy of vestronidase alfa-vjbk were established in clinical trial and expanded access protocols enrolling 23 patients. Efficacy was assessed primarily via the six-minute walk test in 10 patients who could perform the test. After 24 weeks of treatment, the mean difference in distance walked relative to placebo was 18 meters.

The FDA is requiring the manufacturer to conduct a post-marketing study to evaluate the long-term safety of the product.

Source: FDA, November 15, 2017

Vyzulta for Intraocular Pressure

The FDA has approved latanoprostene bunod ophthalmic solution, 0.024% (Vyzulta, Bausch + Lomb), for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

Vyzulta, a once-daily monotherapy, is the first prostaglandin analogue that has nitric oxide (NO) as one of its metabolites. Following topical administration, Vyzulta metabolizes into latanoprost acid, which primarily works within the uveoscleral pathway to increase aqueous humor outflow, and butanediol mono-nitrate, which releases NO to increase outflow through the trabecular meshwork and Schlemm’s canal.

The efficacy and safety of Vyzulta were evaluated in two randomized, multicenter, double-masked, parallel-group phase 3 studies, APOLLO and LUNAR, comparing Vyzulta with timolol maleate ophthalmic solution 0.5% in 831 patients with open-angle glaucoma or ocular hypertension. Vyzulta demonstrated significantly greater IOP lowering than timolol 0.5% throughout the day at three months of treatment, resulting in a reduction in mean diurnal IOP of 32% from baseline.

The most common ocular adverse events included conjunctival hyperemia, eye irritation, eye pain, and instillation site pain. Increased pigmentation of the iris and periorbital tissue and growth of eyelashes can also occur.

Nicox S.A. licensed Vyzulta on a global basis to Bausch + Lomb, which is a subsidiary of Valeant Pharmaceuticals International, Inc.

Source: Valeant, November 2, 2017

Ogivri, a Herceptin Biosimilar

Trastuzumab-dkst (Ogivri, Mylan) has gained FDA approval as a biosimilar to trastuzumab (Herceptin, Genentech) for the treatment of patients with breast or metastatic stomach cancer (gastric or gastroesophageal junction adenocarcinoma) whose tumors overexpress the HER2 gene (HER2+). Ogivri is the first FDA-approved biosimilar for the treatment of breast or stomach cancer.

The FDA’s approval of Ogivri is based on review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Ogivri is biosimilar to Herceptin. Ogivri has been approved as a biosimilar, not as an interchangeable product.

Common expected side effects of Ogivri for the treatment of HER2+ breast cancer include headache, diarrhea, nausea, chills, fever, infection, congestive heart failure, insomnia, cough, and rash. Common expected side effects of Ogivri for the treatment of HER2+ metastatic stomach cancer include neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. Serious expected side effects of Ogivri include worsening of chemotherapy-induced neutropenia.

Like Herceptin, the labeling for Ogivri contains a boxed warning regarding increased risks of cardiomyopathy, infusion reactions, pulmonary toxicity, and embryo-fetal toxicity.

Source: FDA, December 1, 2017

Generic Approvals

Carvedilol Phosphate ER Capsules

The FDA has approved an application for Sun Pharmaceuticals to market carvedilol phosphate extended-release capsules, in 10-mg, 20-mg, 40-mg, and 80-mg doses. Carvedilol phosphate is indicated for the treatment of hypertension. It is the generic form of Coreg CR extended-release capsules (SmithKline Beecham).

Source: FDA, October 25, 2017

Darunavir Ethanolate Tablets

Teva Pharmaceuticals has received permission to market darunavir ethanolate tablets, 600 mg, for the treatment of human immunodeficiency virus-1 infection in adults and children (3 years of age and older). This is the generic version of Prezista (Janssen Pharmaceuticals).

Source: FDA, November 28, 2017

Dapsone Gel, 5%

The FDA has approved Taro Pharmaceutical’s application for dapsone gel, 5%, the generic version of Aczone gel, 5% (Allergan). Dapsone gel is a topical treatment for acne vulgaris.

Source: FDA, October 16, 2017


Gazyva for Untreated Advanced Follicular Lymphoma

The FDA has approved obinutuzumab (Gazyva, Genentech) in combination with chemotherapy, followed by obinutuzumab alone in patients who responded, for previously untreated advanced follicular lymphoma (stage II bulky, III, or IV).

The phase 3 GALLIUM study showed the obinutuzumab-based regimen improved progression-free survival by 28% as a first-line therapy compared with a regimen based on rituximab (Rituxan, Genentech). The most common side effects observed at least 2% more frequently in the obinutuzumab arm included infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation, and diarrhea.

Obinutuzumab is an engineered monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. With the approval, it has three U.S. indications covering certain cases of chronic lymphocytic leukemia and follicular lymphoma. In the United States, obinutuzumab is part of a collaboration between Genentech and Biogen.

Source: Genentech, November 16, 2017

Sutent to Reduce Risk of Kidney Cancer Recurrence

Sunitinib malate (Sutent, Pfizer Inc.) has received FDA approval as the first adjuvant treatment for adults who face a high risk of renal cell carcinoma returning after a nephrectomy.

Sunitinib is a kinase inhibitor that blocks several enzymes that promote cell growth. It was approved in 2006 for the treatment of certain patients with gastrointestinal stromal tumors and advanced renal cell carcinoma. It is also approved for patients with a certain type of pancreatic cancer.

The approval of sunitinib for the adjuvant treatment of renal cell carcinoma was based on a randomized trial of 615 patients with high risk of recurrent renal cell carcinoma following nephrectomy. The study measured the amount of time after the start of the trial that it took for the cancer to come back, for the patient to develop another unrelated cancer, or for death to occur from any cause. After five years, 59.3% of patients treated with sunitinib had not experienced cancer recurrence or death compared with 51.3% of patients receiving placebo.

Common side effects of sunitinib include fatigue, diarrhea, mucositis, stomatitis, nausea, decreased appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension, bleeding events, dysgeusia, dyspepsia, and thrombocytopenia.

The labeling for sunitinib contains a boxed warning to alert health care professionals and patients about the risk of severe liver damage, which may result in liver failure or death.

Source: FDA, November 17, 2017

Sprycel for Children

The FDA has expanded the indication for dasatinib tablets (Sprycel, Bristol-Myers Squibb) to include the treatment of children with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase.

Approval was based on data from 97 pediatric patients with chronic-phase CML evaluated in open-label, nonrandomized phase 1 and phase 2 trials. After 24 months of treatment in these two trials, 96.1% of newly diagnosed patients and 82.6% of patients resistant or intolerant to imatinib had complete cytogenic response.

Adverse reactions reported in more than 10% of dasatinib-treated pediatric patients were headache, nausea, diarrhea, skin rash, vomiting, pain in extremity, abdominal pain, fatigue, and arthralgia.

Sources: Bristol-Myers Squibb and FDA, November 10, 2017

Vimpat for Younger Patients

The FDA has approved a label extension for the antiepileptic drug lacosamide (Vimpat, UCB) as an oral option for the treatment of partial-onset seizures in pediatric patients 4 years of age and older.

The drug is available as an oral solution or tablet for this age group, but use of the injectable formulation is indicated for the treatment of partial-onset seizures only in adult patients (17 years of age and older).

The expanded FDA indication for Vimpat is based on the principle of extrapolation of its efficacy data from adults to children and is supported by safety and pharmacokinetics data collected in children. Adverse reactions in pediatric patients are similar to those seen in adult patients.

Source: UCB, November 6, 2017

Tekturna for Children

Aliskiren oral pellets (Tekturna, Noden Pharma DAC) have received FDA approval for the treatment of hypertension in adults and children 6 years of age and older. The new formulation and pediatric indication were approved through the FDA priority review process.

The efficacy and safety of aliskiren for pediatric use were evaluated in an eight-week randomized, double-blind trial in 267 hypertensive patients 6 to 17 years of age, including 208 patients treated for 52 weeks following the eight-week study. During the initial dose-response phase, aliskiren reduced both systolic and diastolic blood pressure in a weight-based dose-dependent manner.

These studies did not reveal any unanticipated adverse reactions. Adverse reactions in pediatric patients 6 years of age and older are expected to be similar to those seen in adults.

Source: Noden Pharma, November 15, 2017

Vraylar for Maintenance Treatment of Schizophrenia

The FDA has approved cariprazine (Vraylar, Allergan) for the maintenance treatment of adults with schizophrenia. Cariprazine was previously approved for adults for the acute treatment of schizophrenia and acute treatment of manic or mixed episodes of bipolar I disorder.

The efficacy of cariprazine in the maintenance treatment of schizophrenia was based on a multinational, double-blind, placebo-controlled, randomized withdrawal study in the prevention of relapse in adults with schizophrenia. In a 20-week open-label phase, patients with schizophrenia were treated with cariprazine 3 mg, 6 mg, or 9 mg per day. Patients who responded and met the stabilization criteria were then randomized either to continue their cariprazine dose or be switched to placebo for up to 72 weeks or until relapse.

The primary endpoint was time to relapse during the randomized, double-blind phase. Cariprazine significantly delayed the time to relapse compared with placebo. Relapse occurred in nearly twice as many placebo-treated patients (49.5%) as cariprazine-treated patients (29.7%). The safety results were consistent with the profile observed to date for cariprazine, which is an oral, once-daily atypical antipsychotic.

Vraylar carries a boxed warning noting that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Vraylar is not approved for treatment of patients with dementia-related psychosis.

Source: Allergan, November 13, 2017

Adcetris for Cutaneous T-Cell Lymphoma

Brentuximab vedotin (Adcetris, Seattle Genetics, Inc.) has received FDA approval for the treatment of adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF)—the most common subtypes of cutaneous T-cell lymphoma—who have received prior systemic therapy.

Approval was based on a phase 3, randomized, open-label, multicenter clinical trial (ALCANZA) of brentuximab vedotin in patients with MF or pcALCL who had previously received one prior systemic therapy and required systemic treatment. The trial randomized 131 patients (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene. Brentuximab vedotin, compared with physician’s choice, demonstrated significant improvements in objective response rate lasting four months (56% versus 12%), complete response rate (16% versus 2%), and progression-free survival (17 months versus four months).

The most common adverse reactions occurring in more than 20% of patients receiving brentuximab vedotin were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia.

The recommended dose of brentuximab vedotin is 1.8 mg/kg up to a maximum of 180 mg as an intravenous infusion over 30 minutes every three weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity.

The new indication (which received regular approval) is the fourth FDA-approved indication for Adcetris.

Sources: FDA and Seattle Genetics, November 9, 2017

Alectinib for More Lung Cancers

The FDA has granted regular approval to alectinib (Alecensa, Hoffmann-La Roche, Inc./Genentech, Inc.) for the treatment of patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non–small-cell lung cancer (NSCLC) as detected by an FDA-approved test.

In December 2015, alectinib received accelerated approval for treatment of patients with ALK+ metastatic NSCLC whose disease progressed on or who were intolerant of crizotinib (Xalkori, Pfizer) based on overall response rate (ORR) of 38% and 44% among 87 and 138 patients, respectively, in two single-arm trials.

This new approval is based on data from ALEX, a randomized, multicenter, open-label, active-controlled trial in 303 patients with ALK+ NSCLC who had not received prior systemic therapy for metastatic disease. All patients were required to have evidence of ALK rearrangement identified by the VENTANA ALK (D5F3) CDx assay. Patients were randomized 1:1 to receive alectinib 600 mg orally twice daily or crizotinib 250 mg orally twice daily.

For alectinib compared with crizotinib, estimated progression-free survival was 25.7 months versus 10.4 months, respectively; the incidence of the central nervous system as the first site of disease progression (alone or with systemic progression) was 12% versus 45%; and the confirmed ORR was 79% versus 72%. Among alectinib and crizotinib responders, the proportion of patients with response duration of 12 months or longer was 64% and 36%, respectively.

The most common adverse reactions were fatigue, constipation, edema, myalgia, and anemia. Among alectinib-treated patients, adverse reactions led to discontinuation in 11%, dose interruptions in 19%, and dose reductions in 16%.

Source: FDA, November 7, 2017

Zelboraf for Erdheim-Chester Disease

Vemurafenib (Zelboraf, Genentech) has received FDA approval for Erdheim-Chester disease (ECD) with BRAFV600 mutation. ECD is a rare, serious blood disease characterized by the abnormal multiplication of white blood cells called histiocytes, which can invade normal tissues and organs in the body.

The approval is based on data from the phase 2 VE-BASKET study. Basket studies use a clinical trial design that helps collect data faster and may accelerate the development of medicines for diseases with high unmet need. Instead of enrolling people based primarily on their disease or its location, basket studies match a disease’s underlying genetic profile to the mechanism of action of the medicine.

The open-label, nonrandomized VEBASKET study is investigating the use of vemurafenib in BRAFV600 mutation-positive cancers and other diseases, including ECD. Final results for the 22 people with ECD showed a best overall response rate of 54.5% by RECIST v1.1. The median duration of response was not estimable at a median follow-up time of 26.6 months.

The most common adverse events were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags.

Vemurafenib monotherapy was approved for the treatment of people with unresectable or metastatic melanoma with BRAFV600E mutation in 2011.

ECD is an extremely rare non-Langerhans cell histiocytosis. The exact prevalence and incidence of ECD are difficult to ascertain, but it is estimated there are fewer than 500 cases of ECD in the United States. More than 50% of ECD patients have BRAFV600 mutation-positive disease.

Vemurafenib is designed to inhibit some mutated forms of BRAF, which cause abnormal signaling inside cancer cells leading to tumor growth.

Source: Genentech, November 6, 2017


Epinephrine Autoinjector For Infants, Small Children

The FDA has approved an 0.1-mg epinephrine autoinjector (Auvi-Q, kaléo), the first such device specifically designed to treat life-threatening allergic reactions in infants and children weighing 16.5 pounds (7.5 kg) to 33 pounds (15 kg) who are at risk for or have a history of serious allergic reactions.

The new epinephrine autoinjector has a shorter needle and lower dose of epinephrine than current FDA-approved 0.15-mg and 0.3-mg devices. Like other versions of Auvi-Q, the compact device has a voice prompt system that guides a user through the delivery process and has a needle that automatically retracts following administration. The shorter needle was designed to be less likely to strike a pediatric patient’s bone when administering epinephrine in an emergency.

Source: kaléo, November 20, 2017

Cinvanti, IV Aprepitant

The FDA has approved aprepitant injectable emulsion (Cinvanti, Heron Therapeutics, Inc.) for intravenous (IV) infusion for treating acute and delayed chemotherapy-induced nausea and vomiting (CINV).

Aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist, is indicated in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC), including high-dose cisplatin, and nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC).

Aprepitant injectable emulsion is the first polysorbate 80-free, IV formulation of an NK1 receptor antagonist indicated for the prevention of acute and delayed CINV, and is the first IV formulation to directly deliver aprepitant, the active ingredient in Emend capsules (Merck). Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 receptor antagonist to significantly reduce CINV in both the acute phase (0 to 24 hours after chemotherapy) and delayed phase (24 to 120 hours after chemotherapy).

The FDA approval was based on data demonstrating the bioequivalence of aprepitant injectable emulsion to IV fosaprepitant (Emend IV, Merck), supporting its efficacy for the prevention of acute and delayed CINV following HEC and MEC. Results from two pivotal randomized, cross-over bioequivalence studies of aprepitant injectable emulsion and IV fosaprepitant showed patients receiving aprepitant injectable emulsion reported fewer adverse events than those receiving IV fosaprepitant, including substantially fewer infusion-site reactions.

Source: Heron, November 9, 2017


Breakthrough Therapy Status Patisiran for Hereditary ATTR

Amyloidosis With Polyneuropathy

The FDA has granted breakthrough therapy designation for patisiran (Alnylam Pharmaceuticals), an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of adults with hereditary transthyretin-mediated ATTR amyloidosis with polyneuropathy. Hereditary ATTR amyloidosis is an aggressive, rapidly progressing, debilitating and fatal disease.

Patisiran is designed to target specific messenger RNA, potentially blocking the production of TTR protein. This may help clear TTR amyloid deposits and restore function in peripheral tissues.

The designation was based on positive results from APOLLO, a phase 3 randomized, double-blind, placebo-controlled, global study.

Source: Alnylam, November 20, 2017

Patidegib for Gorlin Syndrome

PellePharm has announced that the FDA has granted breakthrough therapy and orphan drug designations to topical patidegib for patients with basal cell carcinoma nevus syndrome (BCCNS).

BCCNS is a genetic disease caused by mutations in the tumor suppressor gene encoding Patched1, which acts as the primary inhibitor of the hedgehog signaling pathway. Also known as Gorlin syndrome, the disease is characterized by hundreds of basal cell carcinomas, especially on the face and sun-exposed areas. There are no FDA-approved therapies for Gorlin syndrome. The standard of care is surgery, but patients with severe disease have as many as 30 surgeries per year, which can be repetitive and scarring.

Topical patidegib was developed to provide the efficacy previously demonstrated by oral patidegib in phase 1 trials, but without the adverse systemic side effects of oral hedgehog inhibitors. The gel has shown early promise in a phase 2 clinical trial by blocking the disease at its source within the hedgehog signaling pathway. Patidegib’s gel formulation is stable at room temperature for at least two years, making it a viable potential therapy for ongoing, at-home management.

PellePharm intends to initiate a phase 3 clinical trial for patidegib in Gorlin syndrome in 2018.

Source: PellePharm, November 20, 2017

Priority Review Designations

Mogamulizumab for Cutaneous T-Cell Lymphoma

The FDA has accepted for priority review the biologics license application (BLA) for mogamulizumab (Kyowa Hakko Kirin) to treat cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.

Mogamulizumab is a humanized monoclonal antibody directed against CC chemokine receptor 4, which is frequently expressed on leukemic cells of certain hematologic malignancies, including CTCL. CTCL is a rare type of non-Hodgkin’s T-cell lymphoma. Depending on the stage, the disease may involve skin, blood, lymph nodes, and viscera. Advanced-stage CTCL is associated with significant morbidity and mortality. The two most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). The FDA granted breakthrough therapy designation status to mogamulizumab for the treatment of MF and SS in patients who have received at least one prior systemic therapy.

The BLA is supported by data from MAVORIC, a phase 3 open-label, multicenter study in 372 patients with MF and SS for whom at least one prior systemic treatment has failed.

Source: Kyowa Hakko Kirin, November 28, 2017

Lofexidine for Opioid Withdrawal

The FDA has granted priority review to the new drug application for lofexidine (U.S. WorldMeds), an investigational product to mitigate opioid-withdrawal symptoms. The application is supported by two randomized, double-blind, placebo-controlled clinical trials and several supporting studies involving more than 1,000 patients.

Opioids lower norepinephrine. With repeated opioid use the brain establishes a new equilibrium by increasing compensatory norepinephrine production to maintain normal functioning. When an opioid is removed or its dose significantly reduced, the brain’s increased norepinephrine levels are no longer offset by the presence of the opioids. This results in a norepinephrine surge that produces the acute and painful symptoms of withdrawal.

Lofexidine, an oral tablet, is a selective alpha 2-adrenergic receptor agonist that reduces the release of norepinephrine. In clinical trials, lofexidine significantly reduced the severity of withdrawal symptoms compared with placebo. If approved, lofexidine would be the first and only nonopioid, nonaddictive medicine for the management of opioid withdrawal

The Prescription Drug User Fee Act action date for lofexidine is set for the second quarter of 2018.

Source: U.S. WorldMeds, November 21, 2017

Abemaciclib for Advanced Breast Cancer

The FDA has granted priority review to abemaciclib (Verzenio, Eli Lilly and Co.) for use as initial treatment for advanced or metastatic breast cancer. The drug received FDA approval in October 2017, but only for use following endocrine therapy. Abemaciclib is currently approved for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer with disease progression following endocrine therapy, and as monotherapy for the treatment of adult patients with HR+, HER2− advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

The new drug application was based upon positive interim results from MONARCH 3, a study of abemaciclib in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of HR+, HER2− advanced or metastatic breast cancer.

Abemaciclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, which are activated by binding to D-cyclins. In estrogen receptor-positive breast cancer cell lines, cyclin D1, CDK4, and CDK6 promote phosphorylation of the retino-blastoma protein, cell cycle progression, and cell proliferation. Abemaciclib disrupts the cell cycle. Preclinically, abemaciclib dosed daily without interruption as a single agent or in combination with antiestrogens reduced tumor size.

Sources: Eli Lilly and Co., October 4 and October 12, 2017

Afatinib for Advanced NSCLC

The FDA has accepted the supplemental new drug application for afatinib (Gilotrif, Boehringer Ingelheim) for priority review. Afatinib is under review for first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 21 (L861Q), G719X, or S768I substitution mutations as detected by an FDA-approved test.

Afatinib is already approved in the U.S. for the first-line treatment of patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations, and with squamous cell carcinoma of the lung whose disease has progressed after treatment with platinum-based chemotherapy. Uncommon mutations, which include L861Q, G719X, or S7681, represent less than 10% of the EGFR mutations found in NSCLC patients and are associated with poor prognosis and survival.

The submission is based on a meta-analysis of three clinical trials from the LUX-Lung clinical trial program that examined the efficacy of afatinib in patients whose tumors have uncommon EGFR mutations. If approved, afatinib would be the first targeted cancer therapy offering the broadest first-line option in EGFR mutation-positive NSCLC.

Source: Boehringer Ingelheim, October 10, 2017

Fast-Track Designations

Aemcolo for Travelers’ Diarrhea

The FDA has granted qualified infectious disease product and fast-track designations for rifamycin SV MMX (Aemcolo, Cosmo Pharmaceuticals), a broad-spectrum, semisynthetic, minimally absorbed antibiotic that can be used to treat bacterial infections of the colon, such as travelers’ diarrhea.

The application of MMX technology to rifamycin SV allows the antibiotic to be delivered directly into the colon, avoiding unwanted effects on the beneficial bacterial flora living in the upper portions of the gastrointestinal tract. The specific dissolution profile of rifamycin SV MMX tablets is thought to increase the colonic disposition of the antibiotic so that an optimized intestinal concentration is achieved, thus abating its systemic absorption in the small intestine.

Phase 3 clinical trials of rifamycin SV MMX in travelers’ diarrhea found it was superior to placebo and noninferior to ciprofloxacin.

Source: Cosmo Pharmaceuticals, October 30, 2017

AGT-181 for Hurler Syndrome

The FDA has granted fast-track designation to AGT-181 (ArmaGen, Inc.), a novel, investigational enzyme replacement therapy for the treatment of somatic and cognitive symptoms in patients with Hurler syndrome.

Hurler syndrome, a severe form of mucopolysaccharidosis type I (MPS I), is a rare, hereditary lysosomal storage disease caused by a deficiency or absence of the enzyme iduronidase, which is needed to break down complex sugars produced by the body. Hurler syndrome affects the brain and spinal cord in children, leading to developmental delay, airway obstruction, corneal and retinal damage, carpal tunnel syndrome, restricted joint movement, progressive mental decline, and impaired language development.

AGT-181 takes advantage of the body’s natural system for transporting proteins and other large molecules noninvasively across the blood–brain barrier (BBB), in this case by binding the same receptor that transports insulin across the BBB into the brain. Initial results from an ongoing phase 2 proof-of-concept study suggested that AGT-181 improves neuro-cognitive function in patients with MPS I.

Source: ArmaGen, Inc., November 30, 2017

Elamipretide for Barth Syndrome

Stealth BioTherapeutics was granted FDA fast-track designation for elamipretide, a treatment for Barth syndrome, a genetic mitochondrial disease caused by mutations in the TAZ gene. The disease is characterized by skeletal muscle weakness, cardiac abnormalities often leading to heart failure, recurrent infections, delayed growth, and reduced life expectancy. Barth syndrome occurs almost exclusively in males and is estimated to affect one in 200,000 to 400,000 people. There are currently no FDA-approved therapies for the disease.

In July 2017, Stealth initiated TAZ-POWER, a phase 2/3, randomized, double-blind, placebo-controlled crossover study to evaluate the effects of daily elamipretide in patients with genetically confirmed Barth syndrome. Top-line results from the study are expected in 2018.

Source: Stealth BioTherapeutics, November 27, 2017

Gilteritinib for Relapsed Or Refractory AML

The FDA has granted fast-track designation for gilteritinib, a treatment for adult patients with FLT3 mutation-positive (FLT3+) relapsed or refractory acute myeloid leukemia (AML). In 2016, approximately 21,000 new patients were diagnosed with AML in the United States.

Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication, as well as FLT3 tyrosine kinase domain, two common types of FLT3 mutations seen in approximately one-third of patients with AML. Gilteritinib has also demonstrated inhibition of AXL, which is reported to be associated with therapeutic resistance.

Astellas Pharma is investigating gilteritinib in various AML patient populations through four ongoing phase 3 trials, including the registrational ADMIRAL trial in relapsed/refractory FLT3+ AML.

Source: Astellas Pharma, October 10, 2017

Orphan Drug Designations

AMV564 for AML

Amphivena Therapeutics, Inc., has received an orphan drug designation for AMV564, a novel CD33/CD3 T-cell engager for the treatment of acute myeloid leukemia (AML) and myelodys-plastic syndromes (MDS).

Amphivena is conducting a phase 1 clinical study of AMV564 in relapsed or refractory AML and plans a phase 1 study in patients with MDS in early 2018.

In preclinical studies, this novel CD33/CD3 bispecific antibody demonstrated potent activity against AML patient samples that was independent of CD33 expression level, disease stage, and cytogenetic risk. The antibody eliminated nearly all blasts from bone marrow and the spleen in a stringent AML patient-derived xenograft murine model. Amphivena also established a therapeutic window for AMV564 in cynomolgus monkeys, with rapid and sustained elimination of CD33-expressing cells during AMV564 dosing and rapid hematopoietic recovery following dosing.

Source: Amphivena Therapeutics, November 29, 2017

Artemisone for Malaria

Artemis Therapeutics has announced that the FDA has granted orphan drug designation for Artemisone for the treatment of malaria.

Artemisone is a potent and fast-acting member of the artemisinin class. In recent years, artemisinin-resistant malaria has become increasingly common. Artemisone may offer a more attractive safety and efficacy profile compared to currently available artemisinins.

In addition to evaluating artemisone for the treatment of Plasmodium falciparum malaria, Artemic is studying its use in human cytomegalovirus (CMV) infections, including stem cell transplant CMV and congenital CMV.

Source: Artemis Therapeutics, November 6, 2017

RT002 for Cervical Dystonia

Revance Therapeutics has been granted an orphan drug designation for daxi-botulinumtoxinA for injection (RT002) to treat cervical dystonia in adults.

Cervical dystonia is a painful condition in which the neck muscles contract involuntarily, causing tonic-clonic movements and awkward posture of the head and neck. Most individuals first experience symptoms in middle age. Treatments include oral medications, botulinum toxin injections, surgery, and complementary therapies. Botulinum toxin can help block the communication between the nerve and the muscle and may alleviate abnormal movements and postures.

In an open-label phase 2 trial, RT002 appeared to be generally safe and well tolerated. At week 4, RT002 showed a clinically significant mean reduction in symptoms of 38% from baseline, 50% at week 6, and 42% at week 12. Reduction was maintained at or above 30% through week 24. Median duration of effect was at least 24 weeks for each dose tested. Current treatment of cervical dystonia calls for injection of botulinum toxin approximately every 12 weeks.

Source: Revance Therapeutics, November 20, 2017

Rare Pediatric Disease Designation

Miransertib for Proteus Syndrome

The FDA has granted a rare pediatric disease designation to miransertib (ArQule, Inc.) for the treatment of Proteus syndrome, a noncancerous segmental overgrowth disorder. “Overgrowth disease” refers to a spectrum of rare diseases identified by somatic mutations, often of the PI3K or AKT1 pathway. The mutations lead to abnormal, often asymmetric, massive growth of the skeleton, skin, adipose tissue, and central nervous system out of proportion to the rest of the body, which may appear normal.

Proteus syndrome is primarily a childhood-onset disease. Although patients may have few or no manifestations at birth, the disease develops and becomes apparent in early childhood (age 6–18 months) and rapidly progresses with intense growth in the first 10 years. Although more than 120 cases have been documented worldwide, it is not known how many people have this disease.

Miransertib is an orally bioavailable, selective small-molecule inhibitor of the AKT kinase. The AKT pathway, when abnormally activated, is implicated in multiple oncogenic processes, such as cell proliferation and apoptosis. Miransertib has been shown preclinically and clinically to inhibit AKT and PI3K cell signaling.

The FDA had previously granted miransertib orphan drug designation. Miransertib has advanced to phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphomas, and tumors harboring either AKT or PI3K mutations. A company-sponsored phase 1/2 trial is being conducted in the U.S. and European Union for overgrowth diseases. Miransertib is also being studied in a phase 1 trial sponsored by the National Institutes of Health for Proteus syndrome. Collaborators are exploring other indications for miransertib, including sickle cell disease, using preclinical testing.

Source: ArQule, Inc., November 1, 2017


Febuxostat and the Heart

Preliminary results from a safety clinical trial show an increased risk of heart-related death with febuxostat (Uloric, Takeda Pharmaceuticals) compared with another gout medicine, allopurinol. The FDA required Takeda to conduct this safety study when the medicine was approved in 2009. Once the final results from the manufacturer are received, the FDA will conduct a comprehensive review and will update the public with any new information.

The safety trial was conducted in more than 6,000 patients with gout treated with either febuxostat or allopurinol. The primary outcome was a combination of heart-related death, nondeadly heart attack, nondeadly stroke, and a condition of inadequate blood supply to the heart requiring urgent surgery. The preliminary results show that overall, febuxostat did not increase the risk of these combined events compared with allopurinol. However, when the outcomes were evaluated separately, febuxostat showed an increased risk of heart-related deaths and death from all causes.

Source: FDA, November 15, 2017


Light Adjustable Lens

The FDA has approved the Light Adjustable Lens (RxSight, Inc.), the first implantable lens that can be tweaked after cataract surgery using ultraviolet (UV) light to improve patients’ vision and potentially eliminate the need for eyeglasses or contacts.

The lens is made of material that reacts to UV light, which is delivered by RxSight’s Light Delivery Device 17 to 21 days after surgery. Patients receive three or four light treatments over one or two weeks, each lasting about 40 to 150 seconds, depending upon the amount of adjustment needed. The patient must wear special eyeglasses for UV protection from the time of the cataract surgery to the end of the light treatments to protect the new lens from UV light in the environment.

In cataract surgery, a cloudy natural lens of the eye is replaced with an artificial intraocular lens (IOL). After surgery, many patients have minor residual refractive error requiring use of glasses or contact lenses.

FDA approval was based on a randomized, pivotal study comparing the Light Adjustable Lens to a commercially available monofocal lens in 600 patients with pre-existing astigmatism. Patients receiving the Light Adjustable Lens, followed by light treatment with the Light Delivery Device, achieved uncorrected visual acuity of 20/20 or better at six months postoperatively at approximately twice the rate of patients receiving a monofocal lens.

The device allows correction of up to 2 diopters of post-operative sphere and/or −0.75 to −2 diopters of residual postoperative refractive cylinder. The device is approved for patients with pre-existing astigmatism of at least 0.75 diopters undergoing cataract surgery who do not have macular diseases. The device should not be used in patients taking systemic medication that may increase sensitivity to UV light or patients with a history of ocular herpes simplex virus.

Sources: FDA and RxSight, Inc., November 22, 2017

Cochlear Implant Can Be Adjusted via Telehealth

The FDA has approved a remote feature for follow-up programming sessions for the Nucleus Cochlear Implant System (Cochlear Americas) through a telemedicine platform. Remote programming is indicated for patients who have had six months of experience with their implant sound processor and are comfortable with the programming process.

Cochlear implants often require regular programming visits with an audiologist. During these visits, the audiologist adjusts electronic settings that control how the implant stimulates the nerves inside the inner ear. This changes how the patient perceives different sounds.

To support the approval of remote programming, the FDA evaluated data from a study of 39 patients, 12 years of age or older, each of whom had a cochlear implant for at least one year. Each patient had one in-person programming session and two remote programming sessions, each approximately two months apart. Speech perception tests a month after each session showed no significant difference between in-person and remote programing. The FDA also evaluated data from patients’ self-assessment of their ability to hear speech in the presence of other sounds and sense the direction, distance, and motion of sound.

Source: FDA, November 17, 2017

NSS-2 Bridge for Opioid Withdrawal

The FDA has cleared an existing electric stimulation device, the NSS-2 Bridge (Innovative Health Solutions, Inc.), for use in helping to reduce the symptoms of opioid withdrawal.

The NSS-2 Bridge is a small electrical nerve stimulator placed behind the patient’s ear. It contains a battery-powered chip that emits electrical pulses to stimulate branches of certain cranial nerves. Such stimulations may provide relief from opioid withdrawal symptoms. Patients can use the device for up to five days during acute physical withdrawal. Opioid withdrawal symptoms can include sweating, gastrointestinal upset, agitation, insomnia, and joint pain.

The FDA reviewed data from a single-arm clinical study of 73 patients who used the device while undergoing opioid physical withdrawal. The study evaluated patients’ clinical opiate withdrawal scale (COWS) score, which measures symptoms. All patients had a reduction in COWS of at least 31% within 30 minutes of using the device.

The FDA cleared the device in 2014 for use in acupuncture. The new use was reviewed through the de novo premarket review pathway.

Source: FDA, November 15, 2017

Genetic Cancer Mutations Test

The FDA has authorized IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets, Memorial Sloan Kettering Cancer Center), a tumor-profiling test that can rapidly identify the presence of mutations in 468 unique genes, as well as other molecular changes in the genomic makeup of a person’s tumor. The results from this next-generation sequencing (NGS) test can provide insight that may help determine how best to treat the cancer.

Unlike many cancer diagnostics that are designed to detect one cancer biomarker for use with a single drug, IMPACT works by comparing tumor tissue to a “normal” sample of tissue or cells from the same patient to detect genetic alterations that might help guide treatment options.

IMPACT’s ability to detect genetic mutations was evaluated for precision, accuracy, and limit of detection. Results indicated that the assay is highly accurate (greater than 99%) and capable of detecting a mutation at a frequency of approximately 5% (range, 2% to 5%). Detection of certain molecular changes (microsatellite instability) using the IMPACT test was concordant more than 92% of the time across multiple cancer types in 175 cases compared with traditional methods of detection.

Along with this authorization, the FDA established a new regulatory pathway for the review of NGS-based tumor-profiling tests for use in patients diagnosed with cancer.

Source: FDA, November 15, 2017

FoundationOne CDx Diagnostic

The FDA has granted marketing approval to the FoundationOne CDx (F1CDx, Foundation Medicine, Inc.), a next-generation sequencing (NGS)-based in vitro diagnostic (IVD) to detect genetic mutations in 324 genes and two genomic signatures in any solid tumor type. The test can also identify which patients with non–small-cell lung cancer, melanoma, breast cancer, colorectal cancer, or ovarian cancer may benefit from 15 different FDA-approved targeted treatment options.

Clinical performance of the test was established through a least burdensome means by comparing the F1CDx to previously FDA-approved companion diagnostic tests that are currently used to determine patient eligibility for certain treatments. Results indicated that the test’s ability to detect select mutation types (substitutions and short insertions and deletions) representative of the entire 324 gene panel is accurate approximately 94.6% of the time.

This is the first device with the FDA’s breakthrough device designation to complete the premarket approval process, and it is the second IVD authorized under the FDA and Centers for Medicare and Medicaid Services’ (CMS) Parallel Review program. Under this program, the CMS issued a proposed national coverage determination of the F1CDx for Medicare beneficiaries with recurrent, metastatic, or advanced stage IV cancer who have not been previously tested using NGS technology and who continue to remain candidates for further therapy.

Source: FDA, November 30, 2017

Nexstim for Depression

The FDA has cleared the NBT system (Nexstim PLC) for marketing for the treatment of major depressive disorder (MDD). Stimulation of the brain through repetitive transcranial magnetic stimulation (TMS) has been demonstrated to be effective in the treatment of MDD in patients who have failed pharmacological treatment.

The NBT system uses an approach known as navigated TMS that allows for accurate, reproducible stimulation of the specific area of the brain associated with the treatment of depression.

Source: Nexstim, November 13, 2017


Philips Defibrillators on Hold Under Federal Court Decree

Philips North America LLC (doing business as Philips Medical Systems and Philips Healthcare) has agreed to a consent decree requiring its Emergency Care and Resuscitation (ECR) unit to cease most operations at facilities in Andover, Massachusetts, and Bothell, Washington, until it corrects problems found by FDA inspectors.

The FDA says Philips manufactured external defibrillators and Q-CPR meters in violation of current good manufacturing practice (CGMP) requirements. The complaint says Philips failed to establish and maintain adequate processes for corrective and preventive actions, design verification and validation controls, and product specifications. Philips must hire a qualified third-party CGMP expert to inspect its ECR business unit to ensure that it meets quality system requirements. After the expert reports to the FDA, the agency will inspect both facilities before allowing Philips to resume manufacturing.

U. S. District Judge Denise J. Casper entered the consent decree, which covers Philips and two company officers, on October 31.

All Philips HeartStart defibrillator products are affected, Philips said, but under certain conditions it can continue to make and ship HeartStart Home and HeartStart OnSite automated external defibrillators and Philips HeartStart FR3 devices. Philips may continue to service and upgrade existing devices.

“Our focus remains on rapidly and effectively returning Philips’ defibrillator manufacturing sites to consistent compliance with quality regulations, as we renew our culture of quality,” Philips said. “It is important to understand that Philips defibrillators and other products manufactured by the affected business remain in use by customers, have strong reliability records, and should not be taken out of service.”

Sources: FDA, November 1, 2017, and Philips, October 11, 2017