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P T. 2017;42(11): 665-672, 691

Drug and Device News November 2017


Verzenio for Breast Cancer

The FDA has approved abemaciclib (Verzenio, Eli Lilly and Co.) to treat adults with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) advanced or metastatic breast cancer that has progressed after endocrine therapy.

Abemaciclib is indicated in combination with the endocrine therapy fulvestrant (Faslodex, AstraZeneca) after cancer has progressed on endocrine therapy. It is also indicated on its own for patients who were previously treated with endocrine therapy and chemotherapy after the cancer had metastasized.

The safety and efficacy of abemaciclib in combination with fulvestrant were studied in a randomized trial of 669 patients with HR+, HER2− breast cancer that had progressed after treatment with endocrine therapy and who had not received chemotherapy once the cancer had metastasized. Median progression-free survival with abemaciclib and fulvestrant was 16.4 months, compared with 9.3 months for placebo and fulvestrant.

The safety and efficacy of abemaciclib as a stand-alone treatment were studied in a single-arm trial of 132 patients with HR+, HER2− breast cancer that had progressed after treatment with endocrine therapy and chemotherapy after the cancer metastasized. The objective response rate was 19.7% in patients taking abemaciclib, lasting for a median 8.6 months.

Source: FDA, September 28, 2017

Fiasp Mealtime Insulin

A fast-acting mealtime form of insulin aspart injection, 100 units/mL (Fiasp, Novo Nordisk), has received FDA approval to improve glycemic control in adults with type-1 and type-2 diabetes.

Fiasp can be dosed at the beginning of a meal or within 20 minutes after starting a meal. It is a new formulation of Novo-Log, with niacinamide (vitamin B3) added to help increase the speed of the initial insulin absorption, resulting in an onset of appearance in the blood in approximately 2.5 minutes. Fiasp will be available in a prefilled delivery device (FlexTouch pen) and a 10-mL vial, and will launch at the same list price as NovoLog.

The approval of Fiasp is based on results from the onset phase 3a clinical development program. The clinical trials enrolled more than 2,000 adults with type-1 and type-2 diabetes to evaluate the efficacy and safety of Fiasp administered both at mealtime and after starting a meal. Data from the trials showed that Fiasp demonstrated a reduction in hemoglobin A1c in adults with type-1 and type-2 diabetes.

Source: Novo Nordisk, September 29, 2017

Mylotarg for AML

The FDA has approved gemtuzumab ozogamicin (Mylotarg, Pfizer) to treat adults with newly diagnosed acute myeloid leukemia (AML) whose tumors express the CD33 antigen. The drug is also approved for patients 2 years of age and older with CD33-positive AML who have relapsed or have not responded to initial treatment.

Gemtuzumab received accelerated approval in May 2000 as a stand-alone treatment for older patients with CD33-positive AML who had experienced a relapse, but it was withdrawn from the market in 2010 after confirmatory trials failed to verify clinical benefit and demonstrated safety concerns. The new approval includes a lower recommended dose, a different dosing schedule, and a new patient population. The FDA said careful review of the new regimen showed that its benefits outweigh its risks.

The safety and efficacy of gemtuzumab in combination with chemotherapy were studied in 271 adults with newly diagnosed CD33-positive AML who were randomized to receive gemtuzumab with daunorubicin and cytarabine or to receive daunorubicin and cytarabine alone. The trial measured event-free survival from the date patients started the trial. Patients who received gemtuzumab with chemotherapy went longer without complications than those who received chemotherapy alone (median event-free survival, 17.3 months versus 9.5 months).

The safety and efficacy of gemtuzumab monotherapy were studied in two trials. The first included 237 patients with newly diagnosed AML who could not tolerate or chose not to receive intensive chemotherapy. Patients were randomized to receive treatment with gemtuzumab or best supportive care. Patients who received gemtuzumab had a median overall survival of 4.9 months versus 3.6 months for best supportive care. The second trial, a single-arm study, included 57 patients with CD33-positive AML who had experienced one relapse. Patients received a single course of gemtuzumab; afterward, 26% achieved a complete remission that lasted a median 11.6 months.

The prescribing information for gemtuzumab includes a boxed warning that severe or fatal hepatotoxicity occurred in some patients who took the drug.

Source: FDA, September 1, 2017

Mvasi, First Cancer Biosimilar

The FDA has approved bevacizumabawwb (Mvasi, Amgen/Allergan) as a biosimilar to bevacizumab (Avastin, Genentech) for the treatment of multiple types of cancer. Mvasi is the first biosimilar approved in the U.S. for cancer treatment.

Bevacizumab-awwb is approved for the treatment of certain colorectal, lung, brain, kidney, and cervical cancers. The FDA’s approval was based on review of extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Mvasi is biosimilar to Avastin. It was approved as a biosimilar, not an interchangeable product.

Like Avastin, the labeling for Mvasi contains a boxed warning about an increased risk of gastrointestinal perforations; surgery and wound-healing complications; and severe or fatal pulmonary, gastrointestinal, central nervous system, and vaginal hemorrhage.

Source: FDA, September 14, 2017

Aliqopa for Relapsed Follicular Lymphoma

The FDA has granted accelerated approval to copanlisib (Aliqopa, Bayer Healthcare Pharmaceuticals) for the treatment of adults with relapsed follicular lymphoma who have received at least two prior systemic therapies.

The approval of copanlisib was based on a single-arm trial that included 104 patients with follicular B-cell non-Hodgkin’s lymphoma who had relapsed disease following at least two prior treatments. The trial measured the overall response rate; 59% of patients had a complete or partial response for a median of 12.2 months.

Serious side effects include infections, hyperglycemia, hypertension, noninfectious pneumonitis, neutropenia, and severe skin reactions.

Source: FDA, September 14, 2017

Trelegy Ellipta for COPD

The FDA has approved once-daily, single-inhaler triple therapy with fluticasone furoate, umeclidinium, and vilanterol (Trelegy Ellipta, GlaxoSmith-Kline/Innoviva, Inc.) for long-term maintenance treatment of patients with chronic obstructive pulmonary disease.

This includes patients with chronic bronchitis and/or emphysema who are on a fixed-dose combination of fluticasone furoate (FF), an inhaled corticosteroid, and vilanterol (VI), a long-acting beta2-adrenergic agonist, for airflow obstruction and reducing exacerbations in whom additional treatment of airflow obstruction is desired. It also includes patients who are already receiving the long-acting muscarinic antagonist umeclidinium (UMEC) and a fixed-dose combination of FF/VI. Trelegy Ellipta is not indicated for relief of acute bronchospasm or the treatment of asthma.

The FDA-approved strength of FF/UMEC/VI is 100/62.5/25 mcg, delivered once daily in GlaxoSmithKline’s Ellipta dry powder inhaler.

Source: GlaxoSmithKline, September 18, 2017

Xhance Nasal Spray

Fluticasone propionate nasal spray (Xhance, Optinose) has received FDA approval for the treatment of nasal polyps in patients 18 years of age and older. The 93-mcg intranasal spray is designed to reach targeted areas deep in the nose with a new exhalation delivery system. The drug is delivered into the nose by actuating the pump spray into one nostril while simultaneously blowing into the mouthpiece of the device.

In phase 3 trials, patients using the spray experienced statistically significant reductions of both nasal congestion and obstruction, as well as total polyp grade.

Source: Optinose, September 18, 2017

Solosec for Bacterial Vaginosis

The FDA has approved secnidazole 2 g oral granules (Solosec, Symbiomix Therapeutics) for the treatment of bacterial vaginosis (BV) in adults. Secnidazole, a next-generation, 5-nitroimidazole antibiotic, is the first single-dose oral therapy for BV and the first new oral antibiotic to treat BV in more than a decade.

Support for the FDA approval included two pivotal trials in BV and an open label safety study. All treatment-emergent adverse events were mild or moderate, and no patients discontinued treatment due to adverse events.

Source: Symbiomix Therapeutics, September 18, 2017

Generic Approvals

Isoproterenol Hydrochloride Injection

The FDA has approved the first generic version of isoproterenol hydrochloride injection (Isuprel, Valeant), a medication that helped fuel debate over costs when Valeant raised the price more than 300% after buying the six-decade-old drug in 2015.

Nexus Pharmaceuticals’ isoproterenol injection, which received expedited review, is available as a single-dose vial containing 0.2 mg/1 mL or 1 mg/5 mL. The drug (first approved in 1956) is used to treat mild or transient episodes of heart block that do not require electric shock or pacemaker therapy; serious episodes of heart block and Adams-Stokes attacks; congestive heart failure; cardiogenic shock; and other serious issues.

Sources: FDA, August 8, 2017; Nexus Pharmaceuticals, August 3, 2017; and FiercePharma, August 7, 2017

Oseltamivir Phosphate For Oral Suspension

Oseltamivir phosphate for oral suspension, 6 mg (base)/mL (Nesher Pharmaceuticals), the generic form of Tamiflu (Roche), has been approved by the FDA. The drug is used to treat influenza A and B in patients 2 weeks of age and older who have had flu symptoms for no more than 48 hours, and to prevent flu in patients 1 year of age and older.

Source: Nesher Pharmaceuticals, September 14, 2017

Tacrolimus Injection

Hospira, Inc., has received approval to market tacrolimus injection in 5-mg/mL, 1-mL single-dose vials. This is the generic version of Astellas’ Prograf, used for prophylaxis of organ rejection in patients receiving allogeneic liver, kidney, or heart transplants.

Source: Hospira, August 25, 2017

Ephedrine Sulfate Injection

Sandoz has received approval for ephedrine sulfate injection USP, 50 mg/mL single-dose vial. This is the generic form of Akovaz (Flamel Ireland), used in the treatment of clinically important hypotension related to anesthesia.

Source: Sandoz, August 23, 2017

Lanthanum Carbonate Chewable Tablets

The FDA has approved Natco Pharma’s application for lanthanum carbonate chewable tablets, the generic form of Fosrenol (Shire), used to reduce serum phosphate in patients with end-stage renal disease. The tablets come in 500-mg, 750-mg, and 1000-mg base doses.

Source: Natco Pharma, August 11, 2017


Opdivo for Liver Cancer

The FDA has approved nivolumab injection for intravenous use (Opdivo, Bristol-Myers Squibb) for the treatment of patients with hepatocellular carcinoma (HCC) who have been treated previously with sorafenib (Nexavar, Bayer Healthcare).

This indication received accelerated approval based on tumor response rate and durability of response. In the CheckMate-040 trial, 14.3% of HCC patients responded to treatment with nivolumab. Among the 22 responders, responses ranged from 3.2 to 38.2-plus months.

Most HCC patients are diagnosed with advanced-stage disease and have limited treatment options.

Source: Bristol-Myers Squibb, September 22, 2017

Keytruda for Stomach Cancer

Pembrolizumab (Keytruda, Merck) has received FDA approval to treat certain patients with recurrent locally advanced or metastatic gastric or gastro esophageal junction adenocarcinoma.

The new indication covers patients whose tumors express programmed death ligand-1 with a combined positive score of at least one as determined by an FDA-approved test and who exhibit disease progression on or after two or more prior lines of therapy, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy.

This indication received accelerated approval based on tumor response rate and durability of response. The KEYNOTE-059 trial included 143 patients similar to the population covered in the new indication. Their objective response rate was 13.3%; among the 19 responding patients, the duration of response ranged from 2.8-plus to 19.4-plus months.

Source: Merck, September 22, 2017

Tracleer for Pediatric PAH

The FDA has approved a new 32-mg tablet for oral suspension for bosentan (Tracleer, Actelion Pharmaceuticals US, Inc.) for use in patients 3 years of age and older with idiopathic or congenital pulmonary arterial hypertension (PAH) to improve pulmonary vascular resistance, which is expected to result in an improvement in exercise ability. Bosentan becomes the first FDA-approved medicine for U.S. children with PAH.

Bosentan is an orally active endothelin receptor antagonist. The 32-mg scored tablet can be dispersed in a teaspoon of water before oral administration. The lower dosage and score lines on the tablets are designed to allow physicians to vary the prescribed dose by patient weight.

Source: Actelion Pharmaceuticals US, Inc., September 6, 2017

Privagen for CIDP

Immune globulin intravenous (human), 10% liquid (Privigen, CSL Behring), has received FDA approval for the treatment of adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability. CIDP is a rare autoimmune disorder that affects the peripheral nerves.

The biologic was initially approved to treat primary immunodeficiency and chronic immune thrombocytopenic purpura in 2007. The approval for CIDP was based on two phase 3 clinical studies. In the PATH study, 73% of the 207 patients receiving Privigen responded over the 13-week course of treatment, as measured by adjusted scores on the Inflammatory Neuropathy Cause and Treatment (INCAT) scale. In the PRIMA study (n = 28), 61% of patients responded to Privigen over 25 weeks as measured by adjusted INCAT scores.

The prescribing information for Privigen includes a boxed warning for thrombosis, renal dysfunction, and acute renal failure.

Sources: CSL Behring and FDA, September 14, 2017

Dotarem for Younger Patients

The FDA has approved gadoterate meglumine (Dotarem, Guerbet LLC USA) for intravenous use with magnetic resonance imaging in patients younger than 2 years of age, including term neonates, to detect and visualize areas with disrupted blood–brain barrier and/or abnormal vascularity of the central nervous system. It was previously approved for this use in patients older than 2 years of age.

The FDA’s review was based on a study showing that at the standard dose (0.1 mmol/kg), the pharmacokinetic and safety profiles in pediatric patients younger than 2 years were similar to those of older children and adults.

Source: Guerbet LLC USA, September 5, 2017

Austedo for Tardive Dyskinesia

Deutetrabenazine (Austedo, Teva Pharmaceutical Industries) is now indicated for the treatment of tardive dyskinesia in adults.

The FDA’s approval was based on results from two phase 3, randomized, double-blind, placebo-controlled, parallel-group studies assessing the efficacy and safety of deutetrabenazine in reducing the severity of abnormal involuntary movements associated with tardive dyskinesia.

Deutetrabenazine was previously approved for the treatment of chorea associated with Huntington’s disease (HD) in April 2017. The drug carries a boxed warning: It can increase the risk of depression and suicidality in patients with HD.

Source: Teva, August 30, 2017

Somatuline Depot For Carcinoid Syndrome

Lanreotide injection 120 mg (Somatuline Depot, Ipsen Biopharmaceuticals, Inc.) has received FDA approval for the treatment of carcinoid syndrome. When used, it reduces the frequency of rescue therapy with a short-acting somatostatin analogue (SSA).

Lanreotide depot, an SSA, is also approved for the improvement of progression-free survival in patients with unresectable, well- or moderately differentiated, locally advanced, or metastatic gastroentero-pancreatic neuroendocrine tumors.

The approval for carcinoid syndrome was based on a 16-week, randomized, double-blind, phase 3 trial. Patients randomized to lanreotide depot/autogel every four weeks needed short-acting octreotide as rescue medication on an adjusted mean of 33.7% of days, compared with 48.5% for placebo.

Sources: Ipsen, September 18, 2017; and Endocrine Practice, September 2016

Aptiom for POS in Children

The FDA has expanded the indication for eslicarbazepine acetate (Aptiom, Sunovion) to include treatment of partial-onset seizures (POS) in children and adolescents 4 to 17 years of age. Eslicarbazepine, administered as a once-daily, immediate-release tablet, is also approved for POS treatment in adults.

The new approval is based on FDA guidance that permits the extrapolation of data to support pediatric use. The safety and efficacy of eslicarbazepine as monotherapy and adjunctive therapy for the treatment of POS in adults were established in five clinical trials. Data from three clinical trials conducted by Sunovion’s partner BIAL, a Portuguese pharmaceutical company, also supported the safety and tolerability of eslicarbazepine for the treatment of POS in pediatric patients. Pharmacokinetic analyses of adult and pediatric data supported the proposed dosing regimen in the pediatric population.

Source: Sunovion, September 14, 2017

Afluria Quadrivalent Flu Vaccine for Age 5 and Up

The FDA has approved Afluria Quadrivalent influenza vaccine (Seqirus) for use in people 5 years of age and older. The vaccine was first approved in August 2016 for people 18 years of age and older to help protect against two influenza A-strain viruses and two B-strain viruses. The traditional seasonal flu vaccine protects against two A strains and a single B strain.

Both Afluria and Afluria Quadrivalent are now licensed and recommended for ages 5 years and up. Both have a needle-free injection delivery option for people ages 18 to 64 years.

In clinical trials, Afluria Quadrivalent demonstrated noninferiority to comparators for all influenza strains contained in the vaccine.

Source: Seqirus, September 14, 2017


Breakthrough Therapy Status

Cemiplimab for Squamous Skin Cancer

Regeneron Pharmaceuticals and Sanofihave received a breakthrough therapy designation for cemiplimab (REGN2810) for patients with metastatic cutaneous squamous cell carcinoma (CSCC) and locally advanced and unresectable CSCC.

Although CSCC has a good prognosis when caught early, it can prove especially difficult to treat in advanced stages. Cemiplimab is an investigational human monoclonal antibody targeting programmed death-1. The companies have reported positive preliminary results from two expansion cohorts in a phase 1 study. EMPOWER-CSCC 1, a phase 2, single-arm, open-label clinical trial, is enrolling patients with metastatic CSCC and locally advanced and unresectable CSCC.

The companies anticipate submitting an application for cemiplimab to the FDA in the first quarter of 2018.

Source: Regeneron Pharmaceuticals, September 8, 2017

Priority Review Designations

CAM2038 for Opioid Use Disorder

The FDA has granted priority review to Camrus and Braeburn Pharmaceuticals for CAM2038 (buprenorphine) depots for adults with opioid use disorder.

The new drug application was based on data from seven clinical trials, including positive results from a pivotal phase 3 trial of weekly and monthly CAM2038 versus daily sublingual buprenorphine/naloxone. The safety profile of CAM2038 was generally consistent with the known safety profile of buprenorphine.

CAM2038 is designed for flexible and individualized treatment from initiation and stabilization to longer-term maintenance therapy, providing sustained buprenorphine release. It comes in prefilled syringes for subcutaneous injection; if approved, it will be offered in dosage strengths of 8 mg to 32 mg for weekly injection and 64 mg to 160 mg for monthly injection.

The FDA has assigned a Prescription Drug User Fee Act target action date of January 19, 2018.

Source: Camrus and Braeburn Pharmaceuticals, September 18, 2017

Pegvaliase for Phenylketonuria

The FDA has accepted the biologics license application for pegvaliase (Bio-Marin) for priority review. Pegvaliase reduces blood phenylalanine (Phe) levels in adults with phenylketonuria (PKU) who have uncontrolled blood Phe levels on existing management.

PKU is caused by a deficiency of phenylalanine hydroxylase (PAH), the enzyme required to metabolize Phe, an essential amino acid found in most protein-containing foods. When PAH is lacking, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, which can cause severe intellectual disability, seizures, tremors, behavioral problems, and psychiatric symptoms. PKU can be managed with a Phe-restricted diet, but adherence can be difficult.

Pegvaliase is an investigational drug that replaces the deficient PAH enzyme with the PEGylated version. In clinical studies, treatment with subcutaneous pegvaliase substantially reduced blood Phe compared with placebo; most patients were able to sustain the Phe reduction long term.

Source: BioMarin, August 29, 2017

Linhaliq for Non-CF Bronchiectasis

Aradigm has received priority review status for Linhaliq for the treatment of non-cystic fibrosis bronchiectasis (NCFBE) patients with chronic Pseudomonas aeruginosa infection.

NCFBE—a rare disease marked by abnormal dilation of the bronchi and bronchioles—is often a consequence of a cycle of inflammation, recurrent lung infections, and bronchial wall damage. NCFBE patients who have chronic P. aeruginosa infections have a 6.5-fold increase in hospitalization, threefold higher mortality, and a worse quality of life than those without P. aeruginosa infections. No drug is approved for this condition. Linhaliq, an investigational proprietary formulation of ciprofloxacin for inhalation, has been studied in two phase 3 trials.

The Prescription Drug User Fee Act goal for action is January 26, 2018.

Source: Aradigm, September 25, 2017

Gazyva for Follicular Lymphoma

Obinutuzumab (Gazyva, Genentech) in combination with chemotherapy, followed by obinutuzumab alone, is receiving FDA priority review for previously untreated follicular lymphoma—a slow-growing, incurable form of non-Hodgkin’s lymphoma characterized by cycles of remission and relapse.

The application is based on results of the phase 3 GALLIUM study of 1,401 patients with previously untreated indolent non-Hodgkin’s lymphoma; 1,202 had follicular lymphoma. Among previously untreated follicular lymphoma patients, progression-free survival improved 32% with treatment based on obinutuzumab compared with rituximab (Rituxan, Genentech) after a follow-up of 41.1 months.

Combination studies investigating obinutuzumab with other approved or investigational medicines are planned or under way across a range of blood cancers.

The FDA is expected to make a decision on approval by December 23, 2017.

Source: Genentech, August 28, 2017

Fast-Track Designations

CPP-1X/sul for FAP

CPP-1X/sul (Cancer Prevention Pharma ceuticals and Sucampo Pharmaceuticals) has been granted fast-track status for adults with familial adenomatous polyposis (FAP), which progresses to colorectal cancer in nearly all patients if left untreated. Currently there is no effective treatment.

CPP-1X/sul is being studied in FAP-310, a randomized, double-blind, phase 3 trial designed to determine if the combination of eflornithine plus sulindac is superior to eflornithine or sulindac as single agents in delaying time to the first occurrence of any FAP-related event. The trial is expected to be completed in 2018 unless extensions are recommended.

Source: Cancer Prevention Pharmaceuticals, September 18, 2017

AT132 for X-Linked Myotubular Myopathy

Audentes Therapeutics has received both fast-track and rare pediatric disease designations for AT132, a gene therapy to treat X-linked myotubular myopathy (XLMTM).

XLMTM is a rare monogenic disease characterized by extreme muscle weakness, respiratory failure, and early death, with an estimated 50% mortality rate by 18 months of age. The disease is caused by mutations in the MTM1 gene, which encodes myotubularin, a protein that plays an important role in the development, maintenance, and function of skeletal muscle cells.

AT132 comprises an AAV8 vector containing a functional copy of the MTM1 gene. Animal studies have demonstrated that a single administration of AT132 improved disease symptoms and survival rates, with no significant AT132-related adverse events or safety findings. Preliminary data from ASPIRO, the phase 1/2 clinical trial of AT132 in patients with XLMTM, are expected later this year.

Source: Audentes Therapeutics, September 27, 2017

Orphan Drug Designations

AMX0035 for ALS

The oral therapeutic AMX0035 (Amylyx Pharmaceuticals) has received orphan drug designation for the treatment of amyotrophic lateral sclerosis (ALS).

AMX0035 combines sodium phenylbutyrate (PB) and tauroursodeoxycholic acid (TUDCA), each of which has demonstrated strong efficacy in cellular and animal models of ALS. When individually tested in ALS clinical trials, PB and TUDCA have shown safety, tolerability, and preliminary signs of efficacy. In preclinical trials, the two compounds had a synergistic effect, suggesting that the combination may be more effective than the individual agents.

Amylyx recently began a 24-week phase 2 trial to evaluate the safety and tolerability of AMX0035 and assess the drug’s impact on disease progression. In an open-label extension, all enrolled patients will have the option of continuing treatment after the 24-week treatment period.

Source: Amylyx Pharmaceuticals, September 19, 2017

DCC-2618 for Glioblastoma Multiforme And Anaplastic Astrocytoma

The FDA has granted orphan drug status to DCC-2618 (Deciphera), a pan-KIT and platelet-derived growth factor receptor alpha (PDGFRα) inhibitor, for the treatment of glioblastoma multiforme and anaplastic astrocytoma. These cancers have an expected two-year survival of 15% to 20%.

DCC-2618 is in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, which also include gastrointestinal stromal tumors and systemic mastocytosis. DCC-2618 is currently in a first-in-human phase 1 clinical trial.

Source: Deciphera, September 5, 2017

ApoGraft for Acute GvHD And Chronic GvHD

The FDA has given an orphan drug designation to ApoGraft (Cellect Biotechnology) for the prevention of acute and chronic graft versus host disease (GvHD) in transplant patients.

In many transplantations—particularly bone marrow transplantations—the transplanted immune mature cells attack the host, leading to severe morbidity and even death. ApoGraft allows stem cells to be selected from any given tissue, separating GvHD-causing cells from stem cells. ApoGraft technology provides enriched stem cells for use as a raw material in a wide range of stem-cell–based therapeutic indications.

Source: Cellect Biotechnology, September 5, 2017


Deaths With Ocaliva

After reports of deaths and serious injuries, the FDA warned that obeticholic acid (Ocaliva, Intercept Pharmaceuticals), which is indicated to treat primary biliary cholangitis (PBC), is being incorrectly dosed in some patients with moderate-to-severe decreases in liver function. However, the drug may also be associated with liver injury in correctly dosed patients with mild disease. “We are working with the drug manufacturer … to address these safety concerns,” the FDA said.

Health care professionals should determine patients’ baseline liver function prior to starting obeticholic acid. Patients with moderate-to-severe liver impairment (Child–Pugh B and C) should be started on the approved dosing schedule of 5 mg once weekly, rather than the 5 mg daily dosing used for other patients. If needed, the dose can rise to a maximum of 10 mg twice weekly. Patients should be monitored frequently for disease progression, and those who develop moderate or severe liver impairment should be switched to the once-or twice-weekly dosing schedule.

In the 13 months after Ocaliva was approved in May 2016, the FDA identified 19 associated deaths. The cause was provided in eight cases: worsening of PBC in seven cases and cardio vascular disease in one. In seven of these eight cases, patients with moderate-to-severe decreased liver function received obeticholic acid 5 mg daily instead of the recommended maximum of 10 mg twice weekly.

The FDA also identified 11 serious liver injuries with obeticholic acid use. Six patients who had moderate or severe decreases in liver function at baseline and developed serious liver injury were receiving obeticholic acid 5 mg daily rather than 10 mg twice weekly as recommended. Three of these six patients died and are included in the 19 deaths cited above. The other five serious liver injuries were reported in patients with no or mild decreases in liver function prior to initiating obeticholic acid. Four of these five patients received obeticholic acid 5 mg daily; the dose was not reported in the fifth case.

Source: FDA, September 21, 2017

Sodium Polystyrene Sulfonate Label Change

The FDA is recommending that patients avoid taking the hyperkalemia drug sodium polystyrene sulfonate at the same time as any other oral medications.

A study found that sodium polystyrene sulfonate binds to many commonly prescribed oral medicines, decreasing the absorption and effectiveness of those other drugs. To reduce this likelihood, the FDA recommends that patients take orally administered prescription and over-the-counter medicines at least three hours before or three hours after sodium polystyrene sulfonate. The agency is updating sodium polystyrene sulfonate drug labels to include this information. Sodium poly styrene sulfonate is sold as Kayexalate (Concordia Pharmaceuticals), as generic brands, and as nonbranded generics.

Sodium polystyrene sulfonate binds with potassium in the intestines so it can be removed from the body. Too much potassium in the blood can cause problems with heart rhythm, which in rare cases can be fatal.

When prescribing sodium polystyrene sulfonate for patients with gastroparesis or other conditions resulting in delayed emptying of food from the stomach into the small intestine, patients should be advised to separate dosing from other orally administered medicines by at least six hours.

Source: FDA, September 6, 2017


Glucose Monitoring System Helps Avoid the “Fingerstick”

The FDA has approved the FreeStyle Libre Flash Glucose Monitoring System (Abbott Diabetes Care, Inc.), which may allow adults with diabetes to dispense with “fingerstick” blood samples.

A small sensor wire inserted below the skin’s surface continuously measures and monitors glucose levels. Patients can determine glucose levels by holding a dedicated mobile reader above the sensor wire to determine if glucose levels are too high or too low and how they are changing. The system is intended for use in people 18 years of age and older with diabetes; after a 12-hour start-up period, it can be worn for up to 10 days.

The FDA evaluated data from a clinical study of individuals 18 years of age and older with diabetes and compared readings obtained by the system to those obtained by an established laboratory method used for analysis of blood glucose.

Risks associated with use of the system may include hypoglycemia or hyperglycemia in cases where information provided by the device is inaccurate and used to make treatment decisions, as well as mild skin irritations around the insertion site. The device does not provide real-time alerts or alarms in the absence of a user-initiated action; for example, it cannot alert users to low blood glucose levels while they sleep.

Source: FDA, September 27, 2017

Mammography Device With Patient-Assisted Compression

The FDA has cleared the first two-dimensional digital mammography system that lets patients increase or decrease the amount of compression applied to their breast before the mammogram x-ray is taken.

A conventional mammogram is a low-dose 2D x-ray of the breast. Digital mammograms use a computer along with x-rays to make and show breast pictures, which are taken in the same way as a conventional mammogram.

The Senographe Pristina with Self-Compression (GE Healthcare) has a hand-held wireless remote control that patients can use to adjust the compression force after breast positioning. During a mammography exam, the technologist positions the patient and initiates compression. The technologist then guides the patient to gradually increase compression using the remote control until adequate compression is reached. The technologist makes the final decision on whether the compression is adequate or needs to be adjusted.

The system was reviewed through the pre-market notification 510(k) pathway.

Source: FDA, September 1, 2017

Easier-to-Clean Duodenoscope

The FDA has cleared the first duodenoscope with a disposable distal cap, which will improve access for cleaning and reprocessing. The Pentax ED34-i10T model duodenoscope (Pentax of America) is intended to provide visualization and access to the upper gastrointestinal (GI) tract to treat bile duct disorders and other upper GI problems.

New features of the device include a single-use, detachable distal cap, simpler user interface, improved ergonomics, improved image quality, and a reduced length.

In fall 2013, the Centers for Disease Control and Prevention alerted the FDA to a potential association between multidrug-resistant bacteria and duodenoscopes. Investigation showed that infections were occurring even when users followed proper cleaning, disinfection, or sterilization instructions. The agency has undertaken steps to reduce the problem.

Sources: FDA, September 20, 2017, and August 23, 2017

Cefaly Migraine Treatment

Cefaly Acute (Cefaly Technology) has received FDA clearance for the acute treatment of migraine, with or without aura, in patients 18 years of age or older. Cefaly’s external trigeminal nerve stimulation (e-TNS) device was already FDA approved for the prevention of migraine attacks.

Proprietary Cefaly technology has been improved to address the different phases of migraines efficiently and safely. Clinical trials demonstrated that one hour of e-TNS with Cefaly Acute can relieve or stop the migraine headache. Results from the ACME (Acute Treatment of Migraine with External trigeminal nerve stimulation) double-blind, randomized, placebo-controlled trial showed that, on average, Cefaly treatment reduced migraine pain by 65%, and 32% of patients were pain free within an hour.

Source: Cefaly Technology, September 21, 2017

Mobile App for Substance Use Disorder

The FDA has cleared marketing of the first mobile medical application to help treat substance use disorders (SUD). The application is meant to be used with outpatient therapy to treat alcohol, cocaine, marijuana, and stimulant SUDs but not to treat opioid dependence.

Reset (Pear Therapeutics) is a mobile app system containing a patient app and clinician dashboard. The device delivers cognitive behavioral therapy to patients to teach them skills that aid in the treatment of SUD and are intended to increase abstinence from substance abuse and increase retention in outpatient therapy programs. The system is intended to be used in conjunction with outpatient therapy and in addition to a contingency management system, a widely used program for treating SUD that uses incentives to reward patients for adherence to their treatment.

The FDA reviewed data from a multisite, unblinded, 12-week clinical trial of 399 patients who received either standard treatment or standard treatment with the addition of a desktop-based version of Reset that could be accessed at the clinic or at home. There was a statistically significant increase in adherence to abstinence for the patients with alcohol, cocaine, marijuana, and stimulant SUD in those who used Reset (40.3%), compared with patients who did not (17.6%).

Reset is indicated as a prescription-only adjunct treatment for patients with SUD who are not on opioid replacement therapy, who do not abuse alcohol solely, or whose primary substance of abuse is not opioids. The device was reviewed through the de novo pre-market review pathway.

Source: FDA, September 14, 2017

Brainlab Spine, Brain Software

Elements Spine SRS and Elements Cranial SRS (Brainlab), software applications that aid patient-specific planning of radiosurgery treatments of the spine and brain, have received FDA clearance.

Brainlab Elements Cranial SRS can create radiosurgery plans in less than 15 minutes from start to finish and supports plans for numerous cranial indications. And while radiosurgery has been used with caution for spine tumors due to the risk of causing damage to the delicate spinal cord, Brainlab Elements Spine SRS helps ensure that high doses of radiation are delivered to the tumor and not the spinal cord itself.

Source: Brainlab, September 21, 2017

FLXfit15 Expandable Cage

The FLXfit15 (Expanding Orthopedics, Inc.) has received FDA 510(k) clearance, enhancing the FLXfit 3D Expandable Cage System. The FLXfit15 will expand surgeons’ flexibility by offering products in different length options with infinitely adjustable expansion and lordosis correction of up to 4 mm and 15 degrees.

Source: Expanding Orthopedics, Inc., September 28, 2017

NaviENT Surgical Navigation

The NaviENT surgical navigation system (ClaroNav) has received FDA 510(k) clearance. NaviENT provides 3D visualization to help surgeons find their ways inside patient sinuses and avoid critical structures, such as the optic nerve and brain, to reach the diseased area safely. NaviENT combines CT scans and real-time information about the exact position of surgical instruments using a stereoscopic optical tracking system.

Source: ClaroNav, September 21, 2017

Wingman14C Crossing Catheter

The Wingman14C Crossing Catheter (Reflow Medical, Inc.) has received FDA 510(k) clearance for use in conjunction with a guide-wire to access discrete regions of the coronary vasculature. Reflow previously received clearance to market Wingman devices for use in the peripheral vasculature. The Wingman14C Crossing Catheter, similar in concept to the devices for the peripheral system, is specifically designed and adapted for use in coronary vasculature and complex below-the-knee lesions.

Source: Reflow Medical, September 26, 2017


FDA Issues Warning Letter To Manufacturer of EpiPen

In a warning letter to the Pfizer subsidiary that makes Mylan’s EpiPen, the FDA says the company “failed to thoroughly investigate multiple serious component and product failures for your EpiPen products, including failures associated with patient deaths and severe illness.”

The letter to Meridian Medical Technologies lists significant violations of current good manufacturing practice requirements at the Missouri facility that makes the EpiPen and EpiPen Jr. The agency directed the company to correct those violations. Among other things, the FDA faulted Meridian’s procedures for investigating complaints, noting that between 2014 and 2017, Meridian “received 171 complaint samples for products that failed to activate when the patient followed the proper sequence.”

In March 2017, Mylan expanded a recall of EpiPen products because of what it called an “extremely rare” component defect that could make the device difficult to activate in an emergency. In September 2017, the FDA said it was not aware of defective EpiPens currently on the market and recommended that consumers use their prescribed device.

In a statement, Pfizer said: “Between September 2015 and now, we have shipped tens of millions of EpiPen Auto-Injectors globally. It’s not unusual to receive product complaints, and each is investigated promptly. There is no information to show that there was any causal connection between complaints of product failure and any patient deaths. We are very confident in the safety and efficacy of EpiPen products being produced at the site.” Mylan also expressed confidence in the safety and efficacy of EpiPen products being produced at the facility.

Sources: FDA, September 5 and 8, 2017; Mylan, March 31 and September 8, 2017; Pfizer, September 14, 2017

Medtronic Infusion Sets

Medtronic PLC is recalling some infusion sets used with its insulin pumps. The recall relates to a discontinued component, the vent membrane, which may be susceptible to fluid blockage during priming/fill-tubing. This can lead to potential overdelivery of insulin shortly after an infusion set change, which may cause hypoglycemia.

Infusion sets manufactured since April 2017 include an updated component that Medtronic believes reduces the risk of insulin overdelivery after an infusion set change. Medtronic will work with patients to replace the recalled infusion sets with new sets at no cost. The list of recalled lots is available via

Source: Medtronic, September 11, 2017

Datascope/MAQUET IABPs

Datascope Corp./MAQUET is recalling all 5,049 CS100i, CS100, and CS300 Intra-Aortic Balloon Pumps (IABPs) manufactured from July 1, 2003, to June 16, 2017, due to false blood detection alarms and ingress of fluid into the IABPs. If a patient requires circulatory support with an IABP and the device does not work, or if therapy is stopped during use without a replacement IABP available, device failure may result in serious adverse consequences, including death.

The pumps in this class 1 recall are cardiac-assist devices used with patients undergoing cardiac and noncardiac surgery, and to treat patients with acute coronary syndrome or complications from heart failure.

Source: FDA, September 6, 2017

Spectranetics Balloon Catheter

Spectranetics is recalling 1,900-plus Bridge Occlusion Balloon Catheters due to the possibility of a blocked guide-wire lumen in some units, which are intended to temporarily block the superior vena cava when emergency control of hemorrhage is required. A blocked guide-wire lumen would prevent proper positioning, and hemorrhage would not be controlled.

The devices were manufactured from February 13, 2017, to July 18, 2017. A list of the 21 lots in the class 1 recall is available at

Source: FDA, September 26, 2017