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P T. 2017;42(5): 296-301,311,335,343

Drug and Device News May 2017

NEW DRUG APPROVALS

Ocrevus for Multiple Sclerosis

The FDA has approved ocrelizumab (Ocrevus, Genentech) as the first medication for both relapsing and primary progressive forms of multiple sclerosis (RMS/PPMS), the forms of the disease that most MS patients have at diagnosis.

Ocrelizumab is a humanized monoclonal antibody designed to selectively target CD20-positive B cells, immune cells thought to be key contributors to myelin and axonal damage that can lead to disability in patients with MS. It is administered by intravenous infusion every six months. The first dose is given as two 300-mg infusions administered two weeks apart. Subsequent doses are given as single 600-mg infusions.

In two phase 3 trials, compared with patients receiving interferon beta-1a, patients treated with ocrelizumab showed significant relative reductions in: annual relapse rates, confirmed disability progression (CDP) for 12 weeks, total number of T1 gadolinium-enhancing lesions, and total number of new or enlarging T2 lesions. In another phase 3 trial, compared with placebo-treated patients, those receiving ocrelizumab demonstrated greater significant relative risk reduction in CDP sustained for at least 12 weeks and a greater improvement in the volume of brain hyperintense T2 lesions.

The most common adverse events associated with ocrelizumab in the phase 3 studies included infusion reactions and upper respiratory tract infections, which were mostly mild-to-moderate in severity.

Source: Genentech, March 28, 2017

Dupixent for Atopic Dermatitis

Dupilumab (Dupixent, Regeneron Pharmaceuticals/Sanofi) has secured FDA approval as the first biologic for the treatment of adults with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupilumab is a human monoclonal antibody that specifically inhibits overactive signaling of two key proteins, interleukin (IL)-4 and IL-13, which are believed to be major drivers of the persistent underlying inflammation in AD.

The approval of dupilumab was based on positive data from three pivotal phase 3 studies that examined the use of dupilumab either alone (SOLO 1 and SOLO 2 trials; total N = 1,379) or with topical corticosteroids (CHRONOS trial; N = 740) in adults with inadequately controlled moderate-to-severe AD. In the SOLO 1 and SOLO 2 studies, respectively, 38% and 36% of patients treated with dupilumab achieved clear or almost clear skin at 16 weeks (the primary endpoint of both studies) compared with 10% and 9% of placebo-treated patients. In the CHRONUS study, 39% of patients treated with dupilumab and corticosteroids achieved clear or almost clear skin at 16 weeks (the study’s primary endpoint) compared with 12% of patients receiving placebo and corticosteroids.

Source: Regeneron, March 28, 2017

Zejula for Ovarian Cancer

The FDA has cleared niraparib (Zejula, Tesaro, Inc.), an oral, once-daily poly(ADP-ribose) polymerase (PARP) inhibitor, for the maintenance treatment of women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have shown a complete or partial response to platinum-based chemotherapy. Niraparib is the first FDA-approved PARP inhibitor that does not require BRCA mutation or other biomarker testing. Tesaro was expected to launch the product in late April.

In the phase 3 ENGOT-OV16/NOVA trial, 553 women with recurrent ovarian cancer received niraparib or placebo until disease progression occurred. Among the patients who were germline BRCA mutation carriers, median progression-free survival (PFS)—the study’s primary endpoint—was 21.0 months for patients treated with niraparib compared with 5.5 months for those given placebo (P< 0.0001). Similarly, in the nongermline BRCA-mutant cohort, the median PFS for patients treated with niraparib was 9.3 months compared with 3.9 months for the placebo arm (P < 0.0001).

Source: Tesaro, March 27, 2017

Bavencio for Merkel Cell Carcinoma

The FDA has given the green light to avelumab injection (Bavencio, EMD Serono) 20 mg/mL, for intravenous use, for the treatment of adults and children 12 years of age and older with metastatic Merkel cell carcinoma (mMCC). Avelumab, a human anti-programmed death ligand-1 (PD-L1) antibody, is the first FDA-approved therapy for patients with mMCC.

The efficacy and safety of avelumab were demonstrated in the JAVELIN Merkel 200 trial—an open-label, single-arm, multicenter study involving 88 patients with histologically confirmed mMCC whose disease had progressed during or after chemotherapy administered for distant metastatic disease. The overall response rate was 33%. Eleven percent of the patients experienced a complete response, and 22% experienced a partial response. Most of the responses (86%) lasted at least six months, and 45% of the responses lasted at least 12 months. The durations of response ranged from 2.8 months to more than 23.3 months.

Source: EMD Serono, March 24, 2017

Symproic for Opioid Constipation

The FDA has approved naldemedine (Symproic, Shionogi Inc./Purdue Pharma) 0.2-mg tablets (C-II) as a once-daily, oral, peripherally acting mu-opioid receptor antagonist for the treatment of opioid-induced constipation in adults with chronic noncancer pain.

Naldemedine is a Schedule II controlled substance because it is structurally related to naltrexone. Shionogi has submitted a petition to the Drug Enforcement Administration requesting that naldemedine’s controlled-substance classification be removed. This request is currently under evaluation. Naldemedine will be jointly launched and commercialized in the U.S. by Shionogi and Purdue Pharma and is expected to be commercially available in mid-summer 2017.

Source: Shionogi, March 24, 2017

Xadago for Parkinson’s Disease

Safinamide (Xadago, Newron Pharmaceuticals) has received FDA approval as an add-on treatment for patients with Parkinson’s disease (PD) who experience “off” episodes while receiving levodopa/carbidopa. An “off” episode is a period when a patient’s medications are not working well, causing an increase in PD symptoms, such as tremor and difficulty walking.

The efficacy of safinamide, a selective monamine oxidase B inhibitor, in treating patients with PD was demonstrated in a trial involving 645 individuals who were also taking levodopa and were experiencing “off” time. The patients treated with safinamide experienced more beneficial “on” time—a period when PD symptoms are reduced—without dyskinesia compared with those receiving placebo. The increase in “on” time was accompanied by a reduction in “off” time and by improved scores on a measure of motor function.

Source: FDA, March 21, 2017

Ribociclib for Breast Cancer

The FDA has approved ribociclib (Kisqali, Novartis) in combination with the aromatase inhibitor letrozole (Femara, Novartis) as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer.

Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that helps slow the progression of cancer by inhibiting cyclin-dependent kinase 4 and 6 proteins. These proteins, when overactivated, can enable cancer cells to grow and divide too quickly.

The FDA’s approval of ribociclib was based on data from a pivotal phase 3 trial that met its primary endpoint early, demonstrating a statistically significant improvement in progression-free survival compared with letrozole alone at the first preplanned interim analysis. Ribociclib was reviewed and approved under the FDA’s breakthrough therapy designation and priority review programs.

Source: Novartis, March 13, 2017

Noctiva for Nocturnal Polyuria

Desmopressin acetate nasal spray (Noctiva, Serenity Pharmaceuticals) has secured FDA approval for the treatment of adults who awaken at least two times per night to urinate because of nocturnal polyuria. Desmopressin nasal spray is the first FDA-cleared treatment for this condition. The spray is used daily, approximately 30 minutes before going to bed. It works by increasing the absorption of water through the kidneys, which leads to less urine production.

The product was approved with a boxed warning and a medication guide because it can cause hyponatremia. It should not be used in patients at increased risk of severe hyponatremia or in patients with symptomatic congestive heart failure or uncontrolled hypertension.

Source: FDA, March 3, 2017

Generic Approvals and Launches

Desvenlafaxine ER Tablets

West-Ward Pharmaceuticals has launched desvenlafaxine succinate extended-release tablets, 50 mg and 100 mg. The product, a generic version of Pristiq (Pfizer), is indicated for the treatment of patients with major depressive disorder. Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor.

Source: Hikma Pharmaceuticals, March 10, 2017

Extended-Release Oxycodone

Daiichi Sankyo Company has launched generic oxycodone extended-release formulations (5 mg, 10 mg, 20 mg, and 40 mg) to treat sustained cancer pain. The product is an opioid analgesic that provides the degree of analgesia prescribed for various cancers with moderate-to-severe pain and is the first generic tablet version of an oxycodone extended-release formulation.

Source: Daiichi Sankyo, March 8, 2017

FDA REVIEW ACTIVITIES

Priority Review Designations

Lynparza for Ovarian Cancer

The FDA has accepted the new drug application (NDA) for olaparib tablets (Lynparza, AstraZeneca) for use in women with platinum-sensitive, relapsed ovarian cancer in the maintenance setting. The FDA also has granted priority review status with an action date set in the third quarter of 2017. The NDA submission included data from the phase 3 SOLO-2 trial, in which olaparib reduced the risk of disease progression by 70% compared with placebo in germline BRCA-mutated patients.

Source: AstraZeneca, March 28, 2017

Solosec for Bacterial Vaginosis

The FDA has granted priority review to secnidazole oral granules (Solosec, Symbiomix Therapeutics), an investigational 5-nitroimidazole antibiotic designed to treat women with bacterial vaginosis. The current recommended regimen of nitroimidazole requires twice-a-day dosing for seven days for a total administration of 7 g of drug.

Source: Symbionix, March 23, 2017

Fast-Track Designation

SHP655 for Thrombotic Thrombocytopenic Purpura

The FDA has granted a fast-track designation to SHP655 (recombinant ADAMTS13, Shire) for the treatment of acute episodes of hereditary thrombotic thrombocytopenic purpura (TTP) in patients with a constitutional deficiency of the von Willebrand factor-cleaving protease ADAMTS13. Hereditary TTP is a life-threatening congenital disease caused by a deficiency in the enzyme ADAMTS13. This deficiency can cause clotting in the microvasculature, with associated organ morbidities. Shire is conducting a phase 3 open-label study of SHP655 in the U.S., Europe, and Japan to determine the compound’s safety and efficacy in the treatment and prevention of acute TTP events in patients with severe hereditary ADAMTS13 deficiency.

Source: Shire, March 22, 2017

Breakthrough Therapy Status

Rituxan for Pemphigus Vulgaris

The FDA has granted breakthrough therapy status to rituximab (Rituxan, Genentech/Roche) for the treatment of patients with pemphigus vulgaris—a rare, life-threatening condition characterized by progressive painful blistering of the skin and mucous membranes. Genentech is enrolling patients with pemphigus vulgaris into a phase 3 study.

Rituximab is currently indicated for use in patients with rheumatoid arthritis or with Wegener’s granulomatosis accompanied by microscopic polyangiitis.

Source: Genentech, March 24, 2017

Qualified Infectious Disease Product Designation

D-Plex for Postsurgical Infection

D-Plex (doxycycline/polymer-lipid encapsulation matrix, PolyPid Ltd.), a secured antibiotic drug reservoir that provides local antibacterial prevention and treatment during surgical procedures, has been designated as a qualified infectious disease product by the FDA.

Sternal infection after cardiac surgery is one of the most significant complications following open cardiac surgery, according to PolyPid. Initial data from an ongoing phase 1b/2 trial of D-Plex showed no sternal infection during a three-month follow-up in treated patients.

Source: PolyPid, March 8, 2017

New and Revised Applications

Fast-Acting Insulin Aspart

Novo Nordisk has resubmitted its new drug application (NDA) for fast-acting insulin aspart to the FDA. In October 2016, the company announced that it had received a complete response letter regarding the original submission. In the letter, the FDA requested additional information related to the assay for immunogenicity and the assay used to generate the clinical pharmacokinetics data before the agency’s review of the NDA could be completed. After an end-of-review meeting with the FDA, Novo Nordisk resubmitted the NDA as a classII resubmission. The company expects to receive feedback from the FDA during the last quarter of 2017.

Source: Novo Nordisk, March 29, 2017

Trulance for IBS-C

Synergy Pharmaceuticals has submitted a supplemental new drug application to the FDA for once-daily plecanatide (Trulance) for the treatment of adults with irritable bowel syndrome with constipation (IBS-C). In January 2017, plecanatide was approved for the treatment of adults with chronic idiopathic constipation.

With the exception of a single amino acid substitution for greater binding affinity, plecanatide is structurally identical to uroguanylin, an endogenous human gastrointestinal peptide. Uroguanylin activates guanylate cyclase-C receptors in a pH-sensitive manner primarily in the small intestine, thereby stimulating fluid secretion and maintaining the stool consistency necessary for regular bowel function.

Source: Synergy Pharmaceuticals, March 27, 2017

Fluarix Quadrivalent Flu Vaccine

GlaxoSmithKline has submitted a supplemental biologics license application to the FDA for Fluarix Quadrivalent influenza vaccine. The product is currently approved for active immunization against influenza A subtype viruses and type B viruses in people 3 years of age and older. The submission seeks an expanded indication for children 6 months through 35 months of age. With this approval, providers would be able to use the same dose of the vaccine (15 mcg of hemagglutinin per virus strain in 0.5 mL) to cover all eligible individuals from the age of 6 months and up.

Source: GlaxoSmithKline, March 15, 2017

Aptiom for Seizures in Children

Sunovion Pharmaceuticals has submitted a supplemental new drug application to the FDA seeking to expand the indication for its antiepileptic drug (AED) eslicarbazepine acetate (Aptiom) to include use as monotherapy or adjunctive therapy for the treatment of partial-onset seizures (POS) in children 4 years of age and older. Eslicarbazepine is the only once-daily, immediate-release AED that is FDA approved for use as monotherapy or adjunctive therapy to treat adult.

Eslicarbazepine is the newest member of the dibenzazepine carboxamide family of AEDs. The precise mechanism(s) by which eslicarbazepine exerts its anticonvulsant activity is unknown but is thought to involve the inhibition of voltage-gated sodium channels.

Source: Sunovion Pharmaceuticals, March 13, 2017

Abaloparatide for Osteoporosis

The FDA has informed Radius Health that it will require additional time to complete its review of the company’s new drug application for subcutaneous abaloparatide. The agency extended the Prescription Drug User Fee Act action date to June 30, 2017. In its letter, the FDA did not request additional information from Radius.

Abaloparatide is an investigational therapy for the potential treatment of women with postmenopausal osteoporosis who are at an increased risk of fracture. Abaloparatide is a synthetic peptide that engages the parathyroid hormone-1 receptor. It was selected for clinical development based on its bone-building activity.

Source: Radius Health, March 10, 2017

Translarna for DMD

The FDA has acknowledged the filing of a new drug application for ataluren (Translarna, PTC Therapeutics), an oral, first-in-class protein-restoration therapy for patients with nonsense-mutation Duchenne muscular dystrophy (nmDMD). The company is seeking approval to market the drug in the United States. Ataluren received marketing authorization for patients with nmDMD in the European Union in August 2014. The FDA has assigned a Prescription Drug User Fee Act action date of October 24, 2017.

Source: PTC Therapeutics, March 6, 2017

DRUG SAFETY ISSUE

Risk of Pancreatitis With Viberzi

The FDA has warned health care professionals that eluxadoline (Viberzi, Allergan), a medication used in patients with irritable bowel syndrome with diarrhea, should not be used in patients who do not have a gallbladder. Hospitalizations and deaths due to pancreatitis have been reported with the use of eluxadoline in these patients, and symptoms of pancreatitis have occurred with only one or two doses of eluxadoline at the recommended dose for patients who do not have a gallbladder (75 mg) and who do not consume alcohol. An FDA review found that these patients have an increased risk of developing serious pancreatitis that could result in hospitalization or death. The FDA is working with Allergan to address these safety concerns.

Source: FDA, March 15, 2017

CLINICAL TRIAL NEWS

Mometasone/Olopatadine Nasal Spray for Allergic Rhinitis

Positive results have been reported for GSP 301 (Glenmark Pharmaceuticals), an investigational fixed-dose combination of mometasone furoate (25 mcg) and olopatadine hydrochloride (665 mcg) administered twice daily as a nasal spray for the treatment of patients with seasonal allergic rhinitis. The findings were from a phase 3 trial that assessed the efficacy and safety of GSP 301 combination therapy compared with that of mometasone alone, olopatadine alone, or placebo.

GSP 301 demonstrated significant improvement from baseline in the average morning and evening patient-reported reflective Total Nasal Symptom Score compared with placebo (P < 0.001), olopatadine (P = 0.028), or mometasone (P = 0.019).

Source: Glenmark Pharmaceuticals, March 29, 2017

Tezacaftor/Ivacaftor for CF

Results from two phase 3 studies of the combination treatment tezacaftor/ivacaftor (VX-661/Kalydeco, Vertex Pharmaceuticals) have shown statistically significant improvements in lung function in patients 12 years of age and older with cystic fibrosis (CF) who have certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Based on the results, Vertex plans to submit a new drug application to the FDA in the third quarter of 2017.

Source: Vertex Pharmaceuticals, March 28, 2017

Sarecycline for Acne

Two phase 3 trials of sarecycline (Allergan/Paratek Pharmaceuticals) evaluating the treatment of inflammatory acne lesions in patients with moderate-to-severe acne have met their 12-week primary efficacy and safety endpoints compared with placebo. Sarecycline is a once-daily, oral, narrow-spectrum tetracycline-derived antibiotic with anti-inflammatory properties. Based on these data, Allergan plans to file a new drug application during the second half of this year.

Source: Allergan, March 27, 2017

CSL830 for Hereditary Angioedema

Positive results have been reported from the phase 3 COMPACT trial, which evaluated the safety and efficacy of CSL830 (CSL Behring)—an investigational, self-administered, subcutaneous (SC) C1-esterase inhibitor (human) replacement therapy—for the prevention of attacks of hereditary angioedema (HAE). The study met its primary efficacy endpoint, significantly reducing the number of HAE attacks. In addition, the study met its secondary endpoints, including the responder rate (i.e., patients who had at least a 50% reduction in their attack rate) and the number of times rescue medications were used. If approved by the FDA, CSL830 would be the only SC preventive therapy for patients with HAE.

Source: CSL Behring, March 22, 2017

Serelaxin for Heart Failure

Disappointing results were reported from a global phase 3 trial investigating serelaxin (Novartis) in patients with acute heart failure (AHF). The study failed to meet either of its coprimary endpoints of a reduction in cardiovascular death through day 180 or reduced worsening heart failure through day 5 when added to standard of care in patients with AHF.

Serelaxin, a relaxin receptor agonist, is a recombinant form of the naturally occurring human relaxin-2 hormone. Human relaxin-2 is present in both men and women, and elevated levels in pregnant women are thought to help the body cope with the additional cardiovascular demands during pregnancy.

In 2014, serelaxin failed to win the approval of U.S. and European regulators, but Novartis pressed on. The drug was originally seen as a way for the company to fill the gap left by expiring patents on heart drugs, such as its own valsartan (Diovan), which lost U.S. rights in 2012.

Sources: Novartis and Reuters, March 22, 2017

Cosentyx for Psoriasis

New data suggest that secukinumab (Cosentyx, Novartis) may modify the course of moderate-to-severe psoriasis, leading to long-term, treatment-free skin clearance. Secukinumab is the only interleukin-17A inhibitor to demonstrate this potential for disease modification.

After one year of treatment with secukinumab, patients were randomly assigned to continuous treatment or treatment cessation until relapse. Patients with continuous treatment maintained their high level of response. In the group that discontinued treatment, 21% of patients maintained skin clearance for up to one year without treatment, and 10% maintained skin clearance after two years without treatment.

Secukinumab is approved for the treatment of patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis.

Source: Novartis, March 21, 2017

Ingrezza for Tardive Dyskinesia

Positive results have been reported from a phase 3 study of valbenazine (Ingrezza, Neurocrine Biosciences), a selective vesicular monoamine transporter 2 inhibitor, for the treatment of patients with tardive dyskinesia. Once-daily valbenazine demonstrated a significant reduction in tardive dyskinesia symptoms compared with placebo in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder.

A new drug application for valbenazine has been granted a priority review, with a Prescription Drug User Fee Act action date of April 11, 2017.

Source: Neurocrine Biosciences, March 21, 2017

JZP-110 for Sleep Apnea

Positive efficacy results have been reported from two global studies of JZP-110 (Jazz Pharmaceuticals) in adults with excessive sleepiness associated with obstructive sleep apnea (OSA). In the TONES 3 trial, JZP-110 demonstrated statistically significant differences in the coprimary efficacy endpoints at doses of 300 mg, 150 mg, 75 mg, and 37.5 mg compared with placebo. These endpoints were the change in mean sleep latency on the Maintenance of Wakefulness Test (MWT) and the change in the Epworth Sleepiness Scale (ESS) from baseline to week 12.

In the TONES 4 study, the JZP-110 treatment arms (300 mg, 150 mg, and 75 mg) again demonstrated statistically significant differences in the coprimary efficacy endpoints (MWT and ESS) compared with placebo at week 6.

JZP-110 is a selective dopamine and norepinephrine reuptake inhibitor in late-stage development for the treatment of excessive sleepiness in adults with narcolepsy or OSA.

Source: Jazz Pharmaceuticals, March 21, 2017

Pembrolizumab for Mesothelioma

Pembrolizumab, an antibody drug used to treat other forms of cancer, may be effective in the treatment of patients with the most common form of mesothelioma, according to investigators at the University of Pennsylvania. Pembrolizumab, a checkpoint inhibitor, has been used to treat melanoma, non–small-cell lung cancer, and head-and-neck cancers.

The KEYNOTE-28 trial evaluated pembrolizumab in 25 adults (18 years of age or older) with malignant pleural mesothelioma. Most of the patients had been treated with chemotherapy. Patients who had received another checkpoint inhibitor were excluded from the study.

Each patient received a dose of pembrolizumab every two weeks. Tumor size was reduced in 14 patients (56%). On average, the patients went approximately six months without disease progression, and overall survival was approximately 18 months. Four patients (16%) were still undergoing treatment after two years.

Source: University of Pennsylvania, March 20, 2017

Abemaciclib for Breast Cancer

The MONARCH 2 trial of abemaciclib (Eli Lilly) has met its primary endpoint of progression-free survival (PFS). The phase 3 study evaluated abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, in combination with fulvestrant in women with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who have relapsed or progressed after endocrine therapy. The addition of abemaciclib to fulvestrant resulted in a statistically significant improvement in PFS compared with the control arm of placebo plus fulvestrant. Lilly intends to submit a new drug application to the FDA for single-agent abemaciclib in the third quarter of 2017.

Source: Eli Lilly, March 20, 2017

Opioid Painkiller NKTR-181

Positive results have been reported from a phase 3, double-blind, randomized study of NKTR-181 (Nektar Therapeutics), the first full mu-opioid agonist molecule designed to provide pain relief without the high levels of euphoria that can lead to abuse and addiction with standard opioids. The FDA has awarded a fast-track designation to NKTR-181 for the treatment of patients with moderate-to-severe chronic pain.

Among study completers, average pain scores increased more in the placebo arm compared with the NKTR-181 arm at week 12 (1.25 for placebo versus 0.56 for NKTR-181; P < 0.0001).

The molecular structure of NKTR-181 is designed to have low permeability across the blood–brain barrier in order to slow its rate of entry into the brain, thereby attenuating the dopamine release that underlies euphoria.

Source: Nektar Therapeutics, March 20, 2017

Repatha to Reduce Apheresis

Positive results have been reported from a phase 3 study evaluating evolocumab (Repatha, Amgen) in patients who were receiving apheresis to reduce low-density lipoprotein-cholesterol (LDL-C) levels. The study met its primary endpoint, demonstrating that treatment with evolocumab significantly reduced the need for LDL-C apheresis in adult patients. The study also met its secondary endpoints of the percent change from baseline to week 4 in LDL-C, in non–high-density lipoprotein-cholesterol (non-HDL-C), and in the total cholesterol:HDL-C ratio. Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9.

Source: Amgen, March 13, 2017

Nucala for Asthma

Patients with severe asthma driven by eosinophilic inflammation who were treated with the biologic agent mepolizumab (Nucala, GlaxoSmithKline) as an add-on to standard of care (SoC) achieved significant improvements in health-related quality of life (hrQOL) and lung function compared with patients treated with placebo and SoC. These results are from the phase 3b MUSCA trial, which successfully met all of its primary and secondary endpoints.

The St. Georges Respiratory Questionnaire score (the study’s primary endpoint), a measure of hrQOL, improved by 7.7 units from baseline with mepolizumab compared with placebo (P = 0.001) after 24 weeks—nearly double the defined clinically meaningful difference of 4.0 units or greater. Lung function (the study’s first secondary endpoint), as measured by prebronchodilator forced expiratory volume in 1 second, increased by 120 mL more (P = 0.001) than in placebo-treated patients at week 24.

Source: GlaxoSmithKline, March 6, 2017

Biosimilar Adalimumab

The phase 3 confirmatory efficacy, safety, and immunogenicity study for biosimilar adalimumab (GP2017, Sandoz/Novartis) met its primary endpoint, demonstrating that GP2017 had efficacy equivalent to that of the reference medication, Humira (AbbVie).

The study’s primary endpoint was the proportion of patients who achieved a 75% improvement at week 16, as measured by the Psoriasis Area and Severity Index (PASI). The results confirmed equivalent efficacy by demonstrating PASI 75 response rates of 67% for GP2017 and 65% for Humira in patients with moderate-to-severe chronic plaque psoriasis. Sandoz plans to seek FDA approval for biosimilar adalimumab in 2017.

Source: Sandoz, March 6, 2017

Guselkumab for Plaque Psoriasis

Janssen Research and Development has reported new findings from pivotal phase 3 studies of guselkumab in adults with moderate-to-severe plaque psoriasis. Data from the VOYAGE 2 study showed that patients treated with guselkumab experienced significant improvements in skin clearance and other measures of disease activity compared with placebo, and significantly greater improvements compared with the anti-tumor necrosis factor-alpha treatment adalimumab (Humira, AbbVie). VOYAGE 2 is the second phase 3 study to demonstrate the superior efficacy of guselkumab versus adalimumab after the VOYAGE1 trial. Data from a third phase 3 study (NAVIGATE) showed that patients who experienced an inadequate response after treatment with the anti-interleukin (IL)-12/23 monoclonal antibody (mAb) ustekinumab (Stelara, Janssen Oncology) and who then switched to guselkumab had significantly greater improvements in skin clearance compared with patients who continued to receive ustekinumab. Guselkumab, a subcutaneously administered anti–IL-23 mAb, is under FDA review for the treatment of adults with moderate-to-severe plaque psoriasis.

Source: Janssen, March 3, 2017

DEVICE APPROVALS

Stealth Staple System

The FDA has granted 510(k) clearance for new additions to the Stealth Staple System (First Ray) product line for intraosseous small-bone fixation. Previously, the company received clearance for its standard-size implants in different lengths, manufactured from titanium alloy. The new FDA clearance includes standard-size implants manufactured from polyetheretherketone (PEEK); small-size implants manufactured from titanium alloy or PEEK; and mini-size implants manufactured from titanium alloy. Standard-size implants are used for hindfoot fusions and first tarsometatarsal joint fusions; small-size implants are used for midfoot fusions, first metatarsophalangeal fusions, and carpal fusions; and mini-size implants are used for carpometacarpal joint fusions, lesser metatarsophalangeal fusions, and the fixation of Akin osteotomies.

Source: First Ray, March 15, 2017

ENFit Low-Dose Tip Syringes

Medela LLC has received 510(k) clearance from the FDA to market ENFit Low-Dose Tip enteral syringes. Specific to enteral feeding, the syringe was created to improve oral medication accuracy, which is necessary for small-volume delivery in neonatal intensive care units. This design helps to improve the accuracy of small-volume enteral drug delivery by preventing unwanted liquid transfer while connecting and disconnecting from the feeding tube, Medela says.

Source: Medela, March 9, 2017

DEVICE SAFETY ISSUES

Cardiovascular Events With Bioresorbable Stent

The FDA has informed health care providers treating patients with the Absorb GT1 bioresorbable vascular scaffold (BVS) (Abbott Vascular) that an increased rate of major adverse cardiac events has been observed in patients receiving the BVS compared with patients treated with the metallic Xience drug-eluting stent (Abbott Vascular).

The BVS is used to open coronary arteries blocked by scar tissue (plaque) in order to increase blood flow to the heart muscle. The BVS is implanted during an angioplasty procedure. It gradually dissolves and is fully absorbed by the body over time.

The FDA’s initial review of two-year data from the pivotal ABSORB III trial found an 11.0% rate of major adverse cardiac events (e.g., cardiac death, heart attack, or the need for an additional procedure to reopen the treated heart vessel) in patients treated with the BVS at two years compared with 7.9% in patients treated with the metallic Xience drug-eluting stent (P = 0.03). This study also showed a 1.9% rate of thrombosis within the BVS compared with a 0.8% rate within the Xience stent at two years. These observed higher adverse cardiac event rates in BVS patients were more likely when the device was placed in small heart vessels.

Source: FDA, March 18, 2017

MedWatch Safety Alerts

The FDA has issued alerts for the following medical devices:

  • HeartStart MRx monitor/defibrillator by Phillips Healthcare: A delay in delivering therapy due to electrical and battery issues could result in serious patient injury, such as permanent organ damage, brain injury, or death. Posted March 24, 2017.
  • Breast implant-associated lymphoma: Breast implant-associated anaplastic large-cell lymphoma is a rare condition. It has been identified most often in patients undergoing implant-revision procedures for late-onset, persistent seroma. Posted March 21, 2017.
  • SynchroMed II and SynchroMed EL implantable drug infusion pumps by Medtronic: Recalled because of failure of priming bolus. Patients may receive a drug overdose or under-dose, which can lead to respiratory depression, coma, or death. Posted March 14, 2017.
  • Balloon angioplasty devices to treat autonomic dysfunction: The FDA is concerned that the procedure may put patients at risk because it is being promoted as a treatment for a variety of conditions even though it has not been studied in clinical trials. Posted March 8, 2017.