Abstract
Approvals, new indications, regulatory activities, and more
NEW DRUG APPROVALS
Amjevita, the First Humira Biosimilar
The FDA has approved Amjevita (adalimumab-atto, Amgen) as a biosimilar to Humira (adalimumab, AbbVie) for the treatment of multiple inflammatory diseases. Amjevita is approved for the following indications in adults: moderately to severely active rheumatoid arthritis; active psoriatic arthritis; active ankylosing spondylitis; moderately to severely active Crohn’s disease; moderately to severely active ulcerative colitis; and moderate-to-severe plaque psoriasis. Amjevita is also indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older.
Source: Amgen, September 23, 2016
Exondys 51 for Duchenne MD
Exondys 51 (eteplirsen injection, Sarepta Therapeutics) has received FDA approval as the first drug indicated to treat patients with Duchenne muscular dystrophy (DMD). The treatment is approved for DMD patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which is found in approximately 13% of this population.
Exondys 51 was approved under the accelerated approval pathway. The FDA is requiring Sarepta to conduct a study to confirm the drug’s clinical benefit. If that trial fails to verify a benefit, the FDA may initiate proceedings to withdraw its approval of the drug.
Source: Sarepta Therapeutics, September 19, 2016
Cuvitru for Primary Immunodeficiencies
The FDA has approved the use of Cuvitru (immune globulin subcutaneous [human], 20% solution, Shire) in adult and pediatric patients 2 years of age and older with primary immunodeficiencies, a group of more than 300 genetic disorders in which part of the body’s immune system is missing or functions improperly.
According to Shire, Cuvitru is the only 20% subcutaneous immunoglobulin (IG) treatment option without proline and with the ability to infuse up to 60 mL (12 g) per site and 60 mL per hour per site, as tolerated, resulting in fewer infusion sites and shorter infusion durations compared with other conventional subcutaneous IG treatments. Regardless of the infusion rate or volume per site, Cuvitru was generally associated with a low incidence of local adverse and systemic reactions (0.022 per infusion and 0.042 per infusion, respectively) in a North American study.
Source: Shire, September 14, 2016
Yosprala to Prevent Cardio- And Cerebrovascular Events
The FDA has approved once-daily Yosprala (Aralez Pharmaceuticals), a fixed-dose combination of enteric-coated aspirin, an antiplatelet agent, and omeprazole, a proton pump inhibitor. The product is indicated for patients who require aspirin for secondary prevention of cardiovascular and cerebrovascular events and who are at risk of developing aspirin-associated gastric ulcers.
Yosprala was designed to support both cardiac and gastric protection for at-risk patients through the proprietary Intelli-COAT system, which is formulated to sequentially deliver immediate-release omeprazole (40 mg) followed by a delayed-release, enteric-coated aspirin core in either 81-mg or 325-mg strengths. The immediate-release omeprazole in Yosprala is designed to elevate the gastric pH into a gastroprotective zone. The enteric-coated aspirin dissolves after the pH has been elevated to 5.5 or greater, thereby reducing the risk of stomach ulcers.
Source: Aralez Pharmaceuticals, September 15, 2016
Generic Approvals and Launches
Memantine ER Capsules
The FDA has approved the first generic versions of memantine hydrochloride extended-release capsules by three companies. Lupin, Ltd., Mylan Pharmaceuticals, Inc., and Sun Pharma Global FZE can sell 7-mg, 14-mg, 21-mg, and 28-mg generic versions of Namenda (Allergan), which is indicated for the treatment of moderate-to-severe dementia of the Alzheimer’s type.
Source: FDA, September 28, 2016
Acetaminophen, Caffeine, and Dihydrocodeine Bitartrate Tablets
The FDA has approved the sale of acetaminophen, caffeine, and dihydrocodeine bitartrate tablets, 325mg, 30 mg, and 16 mg, by Larken Laboratories, Inc. The product is indicated for the relief of moderate to moderately severe pain.
Source: FDA, September 30, 2016
Abacavir Oral Solution
Hetero Labs, Ltd., has secured FDA approval to market abacavir oral solution USP, 20 mg/mL. The FDA describes this as the first generic version of Ziagen oral solution (ViiV Healthcare), which is used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus-1 infection.
Source: FDA, September 26, 2016
Fenofibric Acid DR Capsules
The first generic formulation of fenofibric acid delayed-release (DR) capsules (Trilipix, AbbVie) has secured FDA approval. Impax Laboratories, Inc., can produce 45-mg and 135-mg capsules of the peroxisome proliferator-activated receptor alpha agonist, which is indicated as adjunctive therapy to diet to reduce triglycerides in patients with severe hypertriglyceridemia and to reduce elevated low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and apolipoprotein B and to increase high-density lipoprotein-cholesterol in patients with primary hypercholesterolemia or mixed dyslipidemia.
Source: FDA, September 7, 2016
Abacavir/Lamivudine Tablets
Teva Pharmaceutical Industries has announced the U.S. launch of a generic equivalent of Epzicom (abacavir and lamivudine, ViiV Healthcare/GlaxoSmith-Kline) tablets, 600 mg/300 mg. Abacavir/lamivudine tablets are indicated in combination with other antiretroviral agents for the treatment of patients with human immunodeficiency virus-1 infection.
Source: Teva, September 29, 2016
Buprenorphine/Naloxone Sublingual Tablets
The FDA has approved buprenorphine and naloxone sublingual tablets, 2 mg/0.5 mg and 8 mg/2 mg (Lannett Company)—the therapeutic equivalent to Suboxone sublingual tablets, 2 mg/0.5 mg and 8 mg/2 mg (Indivior, Inc.). Suboxone is used to treat adults who are dependent on opioid drugs.
Source: Lannett Company, September 20, 2016
NEW INDICATION
Orkambi for Cystic Fibrosis
The FDA has approved Orkambi (lumacaftor/ivacaftor, Vertex Pharmaceuticals) for use in children 6 through 11 years of age with cystic fibrosis (CF) who have two copies of the F508del mutation. People with this mutation represent the largest subset of CF patients.
Orkambi is the only medication that treats the underlying cause of CF for people with this mutation. The treatment was previously approved by the FDA for use in people 12 years of age and older with twocopies of the F508del mutation. With the new approval, approximately 11,000 people with CF are eligible for treatment with Orkambi in the United States.
Orkambi combines lumacaftor, which is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del CFTR protein, and ivacaftor, which is designed to enhance the function of the CFTR protein once it reaches the cell surface.
Source: Vertex Pharmaceuticals, September 28, 2016
NEW FORMULATIONS
Invokamet XR for Diabetes
Invokamet XR (Janssen Pharmaceuticals), a combination of canagliflozin and extended-release (XR) metformin, has obtained FDA approval for first-line use as an adjunct to diet and exercise to improve blood glucose control in adults with type-2 diabetes (T2D) when treatment with the two medications is appropriate.
Invokamet XR is a once-daily, fixed-dose combination of canagliflozin (Invokana), the most-prescribed sodium-glucose cotransporter-2 (SGLT2) inhibitor, and XR metformin, which is commonly prescribed as an initial therapy for the treatment of patients with T2D. Canagliflozin works with the kidneys to help adults with T2D lose some sugar through the process of urination, and metformin decreases the production of glucose in the liver and improves the body’s response to insulin.
Invokamet, the first combination of an SGLT2 inhibitor and an immediate-release metformin formulation available in the United States, was approved by the FDA in August 2014 as an adjunct to diet and exercise to improve glycemic control in adults with T2D not adequately controlled with metformin or canagliflozin, or who are being treated with both medications separately. In May 2016, the FDA expanded the Invokamet indication to include adults with T2D who are not being treated with canagliflozin or metformin and may benefit from dual therapy.
Source: Janssen, September 21, 2016
Carnexiv Injection for Seizures
The FDA has approved carbamazepine injection (Carnexiv, Lundbeck) as a short-term (seven-day) replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv received an orphan drug designation from the FDA for this indication and will be the first available intravenous formulation of the anti-epileptic drug carbamazepine. Lundbeck plans to make Carnexiv commercially available in the U.S. in early 2017.
Source: Lundbeck, October 8, 2016
Lomaira for Weight Loss
The FDA has approved phentermine hydrochloride USP 8-mg tablets CIV (Lomaira, KVK Tech, Inc.), a low-dose prescription medication used for a short period (a few weeks) for weight reduction in adults with an initial body mass index of 30 or more (obese) or 27 or more (overweight) with at least one weight-related condition, such as controlled hypertension, diabetes, or hypercholesterolemia. The product should be used with regular exercise and a reduced-calorie diet.
Phentermine, an appetite suppressant, is the most commonly prescribed drug for weight loss. The limited usefulness of agents in this class (anorectics), including phentermine, should be measured against possible risk factors inherent in their use. Phentermine has been associated with pulmonary hypertension, valvular heart disease, palpitations, increased heart rate or blood pressure, insomnia, restlessness, dry mouth, diarrhea, constipation, and changes in sexual drive.
Source: KVK Tech, Inc., September 20, 2016
FDA REVIEW ACTIVITIES
Priority Review Status
Dupilumab for Dermatitis
The FDA has accepted for priority review a biologics license application for dupilumab (Regeneron Pharmaceuticals/Sanofi) for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. The application was given a target action date of March 29, 2017. Dupilumab, an antibody therapy, inhibits the signaling of interleukin (IL)-4 and IL-13, two key cytokines required for the type-2 (including Th2) immune response, which is believed to be a major driver in the pathogenesis of atopic dermatitis.
Source: Regeneron Pharmaceuticals, September 26, 2016
Fast-Track Designations
Galinpepimut-S for Mesothelioma
The FDA has granted fast-track status to the immunotherapy galinpepimut-S (Sellas Life Sciences Group) for the treatment of patients with malignant pleural mesothelioma (MPM). Galinpepimut-S, a WT1 peptide cancer vaccine, is being developed to target hematological cancers and solid tumors, including MPM, acute myeloid leukemia, multiple myeloma, and ovarian cancer. A pivotal phase 3 trial is expected to begin in patients with MPM during the second half of 2017.
Source: Sellas, September 19, 2016
NYX-2925 for Neuropathic Pain
Aptinyx, Inc., is developing NYX-2925, an N-methyl-D-aspartate receptor modulator, for the treatment of pain associated with diabetic peripheral neuropathy. The FDA has designated the investigation of NYX-2925 in this indication as a fast-track program. The safety and tolerability of NYX-2925 are being evaluated in a phase 1, randomized, double-blind, placebo-controlled study in healthy volunteers.
Source: Aptinyx, September 13, 2016
Breakthrough Therapy Status
Tocilizumab for Giant Cell Arteritis
The FDA has granted breakthrough therapy status to tocilizumab (Actemra/RoActemra, Roche), an anti–interleukin-6 receptor biologic, for the treatment of patients with giant cell arteritis, a potentially life-threatening autoimmune condition. The disease is caused by inflammation of large- and medium-sized arteries, most often in the head, but also in the aorta and its branches. Tocilizumab is currently indicated for the treatment of adults with moderately to severely active rheumatoid arthritis.
Source: Roche, October 5, 2016
Glecaprevir/Pibrentasvir for HCV
The FDA has granted breakthrough therapy status to the investigational, pan-genotypic regimen of glecaprevir/pibrentasvir (AbbVie) for the treatment of patients with chronic hepatitis C virus (HCV) infection who failed previous therapy with direct-acting antivirals (DAAs) in genotype 1 (GT1), including therapy with a nonstructural protein 5A inhibitor and/or a protease inhibitor.
Ninety-one percent (20 of 22) of GT1 chronic HCV-infected patients who failed previous therapy with DAAs achieved a sustained viral response at 12 weeks (SVR12) with glecaprevir and pibrentasvir with ribavirin in the primary intent-to-treat analysis. In addition, 86% (19 of 22) of GT1 patients who received glecaprevir and pibrentasvir without ribavirin achieved SVR12. This endpoint was also achieved by 95% of patients with and without ribavirin (20 of 21 and 19 of 20, respectively) in a modified intent-to-treat analysis, which excluded patients who did not achieve SVR for reasons other than virological failure.
Source: AbbVie, September 30, 2016
Orphan Drug Designations
SOR-C13 for Pancreatic Cancer
The FDA has granted orphan drug status to SOR-C13 (Soricimed Biopharma) for the treatment of patients with pancreatic cancer.
SOR-C13 (which previously received orphan drug status for ovarian cancer) is a first-in-class peptide that binds with high selectivity and affinity to TRPV6, a calcium channel that is highly elevated in prostate, breast, lung, and ovarian cancer and is correlated with poor outcomes. By binding to the TRPV6 channel, SOR-C13 starves cancer cells of the calcium that is needed for cell growth and division.
Source: Soricimed Biopharma, September 27, 2016
N-Methanocarbathymidine for Neonatal Herpes Simplex
N-Methanocarbathymidine (N&N Pharmaceuticals) has received an orphan drug designation for the treatment of neonatal herpes simplex. Most neonates (85%) infected with herpes simplex virus-2 (HSV-2) die within one year even after aggressive treatment. Of those who survive, 67% have long-term neuro-developmental problems. Approximately 25% of pregnant women are seropositive for HSV-2 infection, and 1% with a history of recurrent genital HSV-2 infection pass the infection to their newborns. Central nervous system and disseminated neonatal HSV-2 infections are associated with substantial morbidity and mortality resulting from virus-related encephalitis and neutropenia.
Source: N&N Pharmaceuticals, September 27, 2016
Nintedanib for Systemic Sclerosis
The FDA has granted orphan drug status to the kinase inhibitor nintedanib (Ofev, Boehringer Ingelheim) for the treatment of patients with systemic sclerosis (also known as scleroderma), including associated interstitial lung disease (SSc-ILD). The SENSCIS trial, the largest study to date in this disease area, is evaluating nintedanib to understand the disease process and the potential benefit of the compound in patients with SSc-ILD.
The FDA approved nintedanib for the treatment of idiopathic pulmonary fibrosis in October 2014.
Source: Boehringer Ingelheim, September 9, 2016
THN102 for Narcolepsy
THN102 (flecainide acetate/modafinil, Theranexus) has received an orphan drug designation from the FDA for the treatment of patients with narcolepsy, a rare and debilitating sleep/wake disorder. A phase 2 study has been initiated to determine the efficacy of THN102 in this setting.
Source: Theranexus, October 4, 2016
Complete Response Letters
AC-170 for Itchy Eyes
The FDA has issued a complete response letter (CRL) regarding the new drug application for AC-170 (Nicox S.A.), a cetirizine eye-drop formulation for the treatment of ocular itching associated with allergic conjunctivitis. The FDA’s stated reason for the CRL pertained to an inspection at a third-party facility producing the active pharmaceutical ingredient cetirizine and supplying it to Nicox. The FDA did not request additional clinical or nonclinical testing for further review of the AC-170 application.
Source: Nicox, October 10, 2016
Remoxy ER for Pain
Pain Therapeutics has received a complete response letter from the FDA regarding its new drug application for Remoxy ER (oxycodone) extended-release capsules CII. Based on its review, the FDA determined additional actions and data were needed for approval that may take approximately one year to conduct, according to the drug’s developer.
Source: Pain Therapeutics, September 26, 2016
New Applications
Pegfilgrastim Biosimilar Candidate
The FDA has accepted a biologics license application for CHS-1701 (Coherus BioSciences, Inc.), a biosimilar candidate for pegfilgrastim (Neulasta, Amgen). The application is supported by similarity data from analytical, pharmacokinetic, pharmacodynamic, and immunogenicity studies that compared CHS-1701 and Neulasta. An approval decision is expected in June 2017.
Source: Coherus BioSciences, October 6, 2016
Romosozumab for Osteoporosis
The FDA has accepted for review the biologics license application for romosozumab (Amgen/UCB), an investigational monoclonal antibody for the treatment of osteoporosis in postmenopausal women at increased risk of fracture. Romosozumab works by binding to and inhibiting the activity of sclerostin, a protein present in bone, thereby increasing bone formation and decreasing bone resorption. The FDA set a target action date of July 19, 2017.
Source: Amgen, September 26, 2016
Cantrixil for Ovarian Cancer
Novogen, Ltd., has received confirmation from the FDA that its investigational new drug application for cantrixil had been opened and that a phase 1 study of the drug in patients with ovarian cancer may proceed.
Cantrixil is a cyclodextrin-based formulation of TRX-E-002-1, which has shown in vitro and in vivo anticancer activity in a range of tumor types. Novogen anticipates that, if approved, the drug would be used as an intraperitoneal chemotherapy, either alone or in combination with other agents, in one or more cancers of the abdominal or pelvic cavity (e.g., ovarian, uterine, colorectal, or gastric carcinomas). A first-in-human clinical study is planned to start in the fourth quarter of 2016.
Source: Novogen, September 12, 2016
DRUG SAFETY ISSUES
Direct-Acting Antivirals for HCV
The FDA warns that hepatitis B virus (HBV) could become an active infection again in patients who have a current or previous infection with HBV and are treated with certain direct-acting antivirals (DAAs) for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAAs resulted in serious liver problems or death. HBV reactivation usually occurred within four to eight weeks.
As a result, the FDA is requiring a boxed warning about the risk of HBV reactivation to be added to the drug labels of these DAAs, directing health care professionals to screen and monitor for HBV in all patients receiving DAA treatment. This warning will also be included in the patient information leaflets or medication guides for these medications.
Source: FDA, October 4, 2016
I.V. Flush Syringes
Nurse Assist has recalled all unexpired lots of I.V. Flush syringes because of a potential link to Burkholderia cepacia bloodstream infections. According to the Centers for Disease Control and Prevention, the effects of B. cepacia “vary widely, ranging from no symptoms at all to serious respiratory infections, especially in patients with cystic fibrosis.” Nurse Assist voluntarily recalled its I.V. Flush syringes after becoming aware of patients who developed B. cepacia bloodstream infections while receiving intravenous care using prepackaged saline flushes from the company.
Source: FDA, October 5, 2016
CLINICAL TRIAL NEWS
Cabozantinib Outperforms Sunitinib in Renal Cancer
Cabozantinib (Cabometyx, Exelixis, Inc.) demonstrated a 31% reduction in the rate of disease progression or death compared with sunitinib (Sutent, Pfizer) among patients with advanced renal cell carcinoma (RCC) in the CABO-SUN trial (P = 0.012). The phase 2 trial compared cabozantinib with sunitinib in 157 patients with previously untreated advanced RCC with intermediate- or poor-risk disease.
Median progression-free survival for cabozantinib was 8.2 months compared with 5.6 months for sunitinib, corresponding to a 2.6-month (46%) improvement favoring cabozantinib. With a median follow-up of 22.8 months, median overall survival was 30.3 months for cabozantinib compared with 21.8 months for sunitinib (hazard ratio, 0.80).
Source: Exelisis, October 10, 2016
Pembrolizumab for Lung Cancer
Positive results from two major studies of pembrolizumab (Keytruda, Merck), an anti-programmed death therapy, in the first-line treatment of patients with meta-static non–small-cell lung cancer (NSCLC) were presented at the European Society for Medical Oncology 2016 Congress.
The phase 3, randomized KEYNOTE-024 study evaluated pembrolizumab as monotherapy compared with standard-of-care platinum-based chemotherapy in the treatment of 305 patients with squamous and nonsquamous metastatic NSCLC. Pembrolizumab reduced the risk of disease progression or death by 50% compared with chemotherapy (hazard ratio, 0.50; P < 0.001).
The phase 1/2, open-label KEYNOTE-021 trial evaluated the efficacy and safety of pembrolizumab in combination with pemetrexed and carboplatin compared with pemetrexed and carboplatin in a cohort of patients with metastatic, nonsquamous, EGFR- and ALK-negative NSCLC in the first-line treatment setting. Pembrolizumab plus chemotherapy (carboplatin plus pemetrexed) achieved a 55% objective response rate compared with 29% for chemotherapy alone (the standard of care) and reduced the risk of disease progression or death by 47%.
Source: Merck, October 9, 2016
Fulvestrant for Breast Cancer
Fulvestrant (Faslodex) 500 mg demonstrated superior median progression-free survival (PFS) compared with anastrozole (Arimidex) 1 mg in the phase 3 FALCON trial, according to AstraZeneca, which makes both products.
The data relate to the first-line treatment of 462 postmenopausal women with locally advanced or metastatic breast cancer who have not received hormonal treatment for hormone receptor-positive (HR+) breast cancer. Median PFS was 2.8 months longer with fulvestrant than with anastrozole (P = 0.0486). The median PFS was 16.6 months in the fulvestrant arm compared with 13.8 months in the anastrozole arm. Aromatase inhibitors, such as anastrozole, are the current standard of care in the first-line treatment of postmenopausal women with HR+ advanced breast cancer.
Source: AstraZeneca, October 8, 2016
Ataluren for Duchenne MD
PTC Therapeutics has announced data supporting the potential benefit of ataluren, a protein-restoration therapy, in preserving lung function in patients with nonambulatory nonsense mutation Duchenne muscular dystrophy (DMD). The results were based on analyses of lung function data from one of the company’s ongoing open-label extension studies compared with natural history data from a comparable nonambulatory cohort.
In the untreated natural history cohort, forced vital capacity (FVC) peaked at a mean age of 12.5 years and declined thereafter. In comparison, ataluren-treated patients achieved peak FVC at a mean age of 16.5 years. In addition, the absolute FVC was 13.8% higher in ataluren-treated patients compared with untreated patients (P = 0.005), which suggested a slower progression in the loss of lung function in the ataluren group.
Source: PTC Therapeutics, October 6, 2016
Allob for Spinal Fusion
Positive efficacy data have been reported from a phase 2a study of Allob (Bone Therapeutics), a first-in-class allogeneic osteoblastic cell-therapy product, for lumbar spinal fusion. Allob was developed for the treatment of orthopedic conditions and bone diseases. Allogeneic cell therapy involves the harvesting of cells from a healthy donor, rather than from the treated patient.
In the new study, dynamic x-rays showed fusion (i.e., the absence of motion) of the vertebral bodies in six of eight patients at six months and in all patients at nine and 12 months. Fusion was further evidenced by computed tomography scans, which showed the presence of bone bridges in 75% of evaluable patients.
Source: Bone Therapeutics, October 5, 2016
Tildrakizumab for Psoriasis
Tildrakizumab (Sun Pharma), an investigational interleukin (IL)-23p19 inhibitor, has achieved the primary endpoint in two pivotal phase 3 studies involving patients with moderate-to-severe plaque psoriasis. An average of 63% of patients showed 75% skin clearance (Psoriasis Area Sensitivity Index [PASI] 75) by week 12 after two injections of tildrakizumab 100 mg, and 77% showed PASI 75 after 28 weeks and three injections.
Similarly, an average of 57% and 66% of patients had a Physician’s Global Assessment (PGA) score of “clear” or “minimal” with the 100-mg dose at weeks 12 and 28, respectively. In addition, 64% and 78% of patients treated with a 200-mg dose of tildrakizumab achieved PASI 75 at weeks 12 and 28 respectively, and 59% and 69% had PGA scores of “clear” or “minimal” at those time points.
Tildrakizumab is an investigational humanized, anti–IL-23p19 monoclonal antibody designed to selectively block the cytokine IL-23.
Source: Sun Pharma, October 1, 2016
Voclosporin for Lupus Nephritis
Low-dose voclosporin (23.7 mg twice daily) achieved its primary endpoint of complete remission (CR) at 24 weeks in the AURA-LV trial in patients with lupus nephritis, Aurinia Pharmaceuticals announced. In addition, both low-dose and high-dose (39.5 mg twice daily) voclosporin, when added to the current standard of care of mycophenolate mofetil and a forced oral corticosteroid taper, met all 24-week secondary endpoints compared with the control group. Among these endpoints, the time to CR was 19.7 weeks for low-dose voclosporin and 23.4 weeks for high-dose voclosporin compared with “not achieved” for the control group (P < 0.001 and P = 0.001 for the two voclosporin doses versus control). Partial remission was achieved by 70% of the low-dose group (P = 0.007) and by 66% of the high-dose group (P = 0.024) compared with 49% of the control group.
Source: Aurinia Pharmaceuticals, September 29, 2016
ITI-007 for Schizophrenia
Disappointing results were reported from the second phase 3 trial of ITI-007 (Intra-Cellular Therapies, Inc.), an oral, first-in-class investigational medication for the treatment of patients with schizophrenia. Neither dose of ITI-007 was significantly different from placebo on the study’s primary endpoint—the change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score.
ITI-007 20 mg and 60 mg demonstrated reductions from baseline on the PANSS total score of 15.0 points and 14.6 points, respectively, compared with a reduction of 15.1 points with placebo. In contrast, the active control, risperidone, demonstrated a 20.5-point reduction from baseline.
Source: Intra-Cellular Therapies, September 28, 2016
Erenumab for Migraine
A phase 3 study of the investigational migraine treatment erenumab (Amgen/Novartis) has met its primary endpoint, demonstrating a statistically significant reduction from baseline in monthly migraine days in patients with episodic migraine compared with placebo at 12 weeks (2.9 days versus 1.8 days, respectively). Erenumab, a fully human monoclonal antibody, was designed to target and block the calcitonin gene-related peptide receptor, which is believed to have a critical role in mediating migraine pain. Source: Amgen, September 28, 2016
Zykadia for Lung Cancer
Positive results have been reported from a phase 3 study of ceritinib (Zykadia, Novartis) in patients with advanced anaplastic lymphoma kinase-positive (ALK+) non–small-cell lung cancer (NSCLC). The multicenter, randomized trial, which assessed the efficacy and safety of ceritinib in previously untreated adults, met its primary endpoint, demonstrating a clinically significant improvement in progression-free survival compared with standard chemotherapy, including maintenance.
Ceritinib is an oral, selective inhibitor of ALK, a gene that can fuse with others to form an abnormal “fusion protein” that promotes the development and growth of certain tumors in cancers, including NSCLC. In the U.S., ceritinib was granted accelerated approval for the treatment of patients with ALK+ metastatic NSCLC who have progressed on or are intolerant of crizotinib.
Source: Novartis, September 23, 2016
Dasotraline for ADHD
A pivotal study evaluating dasotraline (Sunovion Pharmaceuticals), a dopamine and norepinephrine reuptake inhibitor, in children with attention-deficit/hyper-activity disorder (ADHD) has met its primary efficacy endpoint.
The six-week SEP360-202 trial was a phase 2/3, randomized, double-blind, multicenter, placebo-controlled, parallel-group, fixed-dose safety and efficacy study that evaluated once-daily dasotraline (2 mg or 4 mg per day) in 342 children 6 to 12 years of age with ADHD. The study’s primary efficacy endpoint was the change from baseline to week 6 in the ADHD Rating Scale-IV: Home Version total score. The 4-mg dosage arm demonstrated a statistically significant and clinically relevant difference compared with placebo. The 2-mg dosage arm was not significantly different from placebo.
Source: Sunovion, September 20, 2016
Vepoloxamer for Sickle Cell Disease
Disappointing results have been reported from a phase 3 study of vepoloxamer (Mast Therapeutics) for the treatment of individuals with sickle cell disease experiencing vaso-occlusive crisis (VOC). The study did not meet its primary efficacy endpoint of demonstrating a statistically significant reduction in the mean duration of VOC (82 hours in the vepoloxamer group versus 78 hours in the placebo group; P = 0.09). Moreover, there were no statistically significant differences between the two treatment groups in the rate of rehospitalization for VOC and the occurrence of acute chest syndrome (secondary efficacy endpoints).
Vepoloxamer is purified poloxamer 188—a nonionic block copolymer. Its hydrophobic polyoxypropylene core is believed to adhere to hydrophobic domains exposed on damaged cell membranes, thereby restoring membrane integrity and reducing surface tensions that otherwise promote pathologic adhesive interactions. As the damaged area of the cell membrane repairs, vepoloxamer is removed from the cell surface and excreted from the body, unchanged, primarily in the urine.
Source: Mast Therapeutics, September 20, 2016
Romosozumab for Osteoporosis
Findings from a phase 3 study have shown that the investigational agent romosozumab (Amgen/UCB) significantly reduced the incidence of new vertebral fractures in post-menopausal women with osteoporosis through 12 and 24 months, meeting the study’s coprimary endpoints. The results from this study, the first to evaluate fracture risk reduction as early as one year as a primary endpoint, were published in the New England Journal of Medicine.
Romosozumab works by binding to and inhibiting the activity of the protein sclerostin. As a result, the treatment has a dual effect on bone, both increasing bone formation and decreasing bone breakdown.
Source: Amgen, September 18, 2016
Siponimod for Progressive MS
Positive results have been reported from a phase 3 study of oral once-daily siponimod (Novartis), a selective sphingosine-1-phosphate receptor modulator, in patients with secondary progressive multiple sclerosis (MS). Treatment with siponimod reduced the risk of three-month confirmed disability progression by 21% compared with placebo (P = 0.013). Moreover, a significant difference in favor of siponimod was observed in the annualized relapse rate; the percent change in brain volume; and the change from baseline in the volume of T2 lesions (i.e., brain lesions identified by a T2-weighted magnetic resonance imaging scan).
Source: Novartis, September 17, 2016
Lasmiditan for Migraine
The pivotal phase 3 SAMURAI trial evaluating lasmiditan (CoLucid Pharmaceuticals) has achieved its secondary endpoints with statistical significance. SAMURAI was a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of lasmiditan (100 mg and 200 mg) in comparison with placebo in patients with migraine. Both lasmiditan doses were efficacious in terms of freedom from headache pain and freedom from the most bothersome symptom at two hours (P < 0.001), the study’s primary and key secondary endpoints. Lasmiditan selectively targets 5-HT1F receptors expressed in the trigeminal pathway.
Source: CoLucid Pharmaceuticals, September 17, 2016
Semaglutide for Diabetes Cardiac Risk
Semaglutide (Novo Nordisk) significantly reduced the risk of the primary composite endpoint—time to first occurrence of cardiovascular (CV) death, non-fatal myocardial infarction, or nonfatal stroke—by 26% compared with placebo when added to standard of care among 3,297 adults with type-2 diabetes at high CV risk in the SUSTAIN 6 trial.
Semaglutide is an investigational glucagon-like peptide-1 analogue. SUSTAIN 6 was an international, randomized, double-blind, placebo-controlled premarketing CV outcomes trial investigating the long-term effects of semaglutide (0.5 mg and 1.0 mg) administered once weekly compared with placebo. Standard of care included lifestyle modifications, glucose-lowering treatments, and CV medications.
Source: Novo Nordisk, September 16, 2016
Sublingual Sufentanil for Pain
In an open-label phase 3 trial, the investigational product ARX-04 (sufentanil sublingual tablets 30 mcg, AcelRx Pharmaceuticals) was well tolerated in the management of moderate-to-severe acute pain in postoperative patients, including elderly patients and those with organ impairment. Regardless of age and organ function, 63% of the patients experienced no adverse events during the study. In a global assessment of ARX-04 as a method of pain control, 90% of health care professionals and 87% of patients responded that the treatment was “good” or “excellent.” ARX-04 tablets are delivered sub-lingually by a health care professional using a disposable, prefilled, single-dose applicator.
Source: AcelRx Pharmaceuticals, September 15, 2016
Shingrix Vaccine for Shingles
Results from a phase 3 study of the investigational shingles vaccine Shingrix (GlaxoSmithKline) have shown 90% efficacy in adults 70 years of age and older, which was maintained for at least four years. Shingrix is a nonlive, adjuvanted, subunit candidate vaccine to help prevent herpes zoster and its complications. The vaccine combines glycoprotein E, a protein found on the varicella zoster virus that causes shingles, with an adjuvant system, AS01B, which is intended to enhance the immunological response to the antigen.
Source: GlaxoSmithKline, September 14, 2016
Raxone for Muscular Dystrophy
Data from a pivotal phase 3 study demonstrate the positive effect of idebenone (Raxone, Santhera Pharmaceuticals) on inspiratory function in patients with Duchenne muscular dystrophy (DMD).
The DELOS trial evaluated the effect of idebenone on the maximum inspiratory flow (V’I, max) generated during a forced vital capacity (FVC) maneuver. Patients in the study’s two treatment groups—idebenone (n = 31) and placebo (n = 33)—had comparable and abnormally low V’I, max(FVC) at baseline. During the study period, V’I, max(FVC) further declined by −0.29 L per second (L/s) in patients receiving placebo at week 52 (P = 0.008) but remained stable in patients treated with idebenone (change from baseline to week 52: 0.01 L/s; P= 0.950). The between-group difference demonstrated a positive treatment effect for idebenone of 0.27 L/s (P = 0.043) at week 26 and 0.30 L/s (P = 0.061) at week 52.
Source: Santhera Pharmaceuticals, September 13, 2016
Sotagliflozin for Type-1 Diabetes
A pivotal phase 3 study of oral sotagliflozin (Lexicon Pharmaceuticals) showed a statistically significant reduction in hemoglobin A1c (HbA1c) at 24 weeks in patients with type-1 diabetes on a background of optimized insulin.
Patients treated with sotagliflozin had a mean HbA1c reduction from baseline of 0.43% on a 200-mg once-daily dosage (P < 0.001) and a reduction of 0.49% on a 400-mg once-daily dosage (P < 0.001) compared with a reduction of 0.08% with placebo after 24 weeks of treatment, meeting the study’s primary endpoint.
Sotagliflozin is a first-in-class, oral dual inhibitor of sodium-glucose cotransporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose reabsorption by the kidneys.
Source: Lexicon Pharmaceuticals, September 9, 2016
DEVICE APPROVALS
Automated Insulin Delivery Device for Type-1 Diabetes
The FDA has approved the MiniMed 670G hybrid closed-looped system (Medtronic), the first agency-approved device that is intended to automatically monitor glucose and provide appropriate basal insulin doses in people 14 years of age and older with type-1 diabetes.
The MiniMed system, often referred to as an “artificial pancreas,” is intended to adjust insulin levels with little or no input from the user. It works by measuring glucose levels every five minutes and automatically administering or withholding insulin. The system includes a sensor that attaches to the body to measure glucose levels under the skin; an insulin pump strapped to the body; and an infusion patch connected to the pump with a catheter that delivers insulin. While the device automatically adjusts insulin levels, users must manually request insulin doses to counter carbohydrate (meal) consumption.
Source: FDA, September 28, 2016
Diabetes Sensing System
The FDA has approved the FreeStyle Libre Pro system (Abbott), a continuous glucose monitoring system for diabetes patients. A clinician applies a small, round sensor to the back of the patient’s upper arm. The water-resistant, disposable sensor is held in place with a self-adhesive pad and remains on the back of the arm for up to 14 days, requiring no patient interaction with the device or the need for the patient to draw blood via a finger stick to calibrate the sensor.
The sensor continuously measures glucose in interstitial fluid through a small (5-mm by 0.4-mm) filament that is inserted under the skin. This filament records glucose levels every 15 minutes, capturing up to 1,340 glucose results for up to 14 days, giving treating doctors comprehensive data for complete glycemic profiles of their patients. After 14 days, the patient returns to his or her doctor’s office, where the doctor uses a FreeStyle Libre Pro reader to scan the sensor and to download the 14-days’ worth of glucose results, which are stored in the sensor. The process takes as little as five seconds.
Source: Abbott, September 28, 2016
Obalon for Weight Loss
The FDA has given the green light to the Obalon Balloon System (Obalon Therapeutics), a nonsurgical, fully reversible device for weight loss. The intragastric balloon system is indicated for temporary use to facilitate weight loss in adults with obesity (i.e., a body mass index of 30 to 40 kg/m2) who have failed to lose weight through diet and exercise. The system is intended to be used as an adjunct to a moderate-intensity diet and behavior-modification program.
The system consists of a balloon folded inside a capsule that is swallowed by the patient, with no sedation or anesthesia required. Once the balloon reaches the stomach, it is remotely inflated with gas via a microcatheter, which is then removed, leaving a lightweight, buoyant balloon in the stomach. During the next three months of treatment, two additional balloons are swallowed and inflated. At the end of the six-month treatment period, all three balloons are removed via outpatient endoscopy under conscious sedation.
Source: Obalon Therapeutics, September 12, 2016
Mi-eye 2 Lets Doctors Visualize Joint Injuries
The FDA has cleared mi-eye 2 (Trice Medical), a disposable needle with a fully integrated camera and light source that allows physicians to use diagnostic imaging to visualize joint injuries in their clinics. The device is designed for use in diagnostic and operative arthroscopic and endoscopic procedures to provide illumination and visualization through either a natural or surgical opening. The mi-eye 2 also gives physicians the ability to inject or aspirate under direct visualization.
Source: Trice Medical, October 6, 2016
Disposable Colonoscope
The FDA has granted 510(k) clearance for the Aer-O-Scope (GI View Ltd.), a disposable, self-propelled, joystick-controlled colonoscope system. The new device allows therapeutic access using standard tools, such as snares and forceps, to obtain biopsies or to perform polypectomies. According to the manufacturer, the Aer-O-Scope is the first colonoscope to provide 360-degree visualization of the colon to detect polyps behind folds. In addition, there is no risk of contamination or disease transmission between patients from the device because it is used only once and then discarded.
Source: GI View, September 20, 2016
Kyleena Contraceptive Device
The FDA has approved Kyleena (levonorgestrel-releasing intrauterine system, Bayer), a progestin-containing intrauterine system, for the prevention of pregnancy for up to five years. Kyleena is a small, flexible, plastic T-shaped device containing 19.5 mg of the progestin hormone levonorgestrel. The device is placed by a health care provider during an office visit and may be removed by a health care provider at any time.
Source: Bayer, September 19, 2016
Aera for Dysfunction Of the Eustachian Tube
The FDA has permitted marketing of the Aera system (Acclarent, Inc.), which uses a small balloon to treat persistent eustachian tube dysfunction, a condition in which pressure, pain, or clogged or muffled sensations occur in the ear. With the Aera system, a doctor uses a catheter to insert a small balloon through the patient’s nose and into the eustachian tube. Once inflated, the balloon opens a pathway for mucus and air to flow through the eustachian tube, which may help restore proper function. After the eustachian tube is dilated, a doctor deflates and removes the balloon.
Source: FDA, September 16, 2016
OTHER DEVICE NEWS
Rezūm System for BPH
NxThera has launched the Rezūm system for the treatment of men with benign prostatic hyperplasia (BPH). Administered by urologists in an office-based procedure, the system uses stored thermal energy in water vapor (steam) created with a radiofrequency current to treat enlarged prostate tissue, which can cause bothersome symptoms, such as urinary frequency and urgency; irregular or weak urinary flow; straining during urination; and getting up frequently at night to urinate.
The Rezūm procedure is performed using oral sedation and/or local anesthesia. Studies have reported clinically significant improvements in BPH symptoms within two weeks, with continued improvement for three months, after which the improvements were consistent and durable, with no impairment of sexual function.
Source: NxThera, October 3, 2016
Hemoperfusion for Sepsis
Disappointing results have been reported from a pivotal phase 3 trial of the Toraymyxin therapeutic hemoperfusion device (Spectral Medical Inc.), which removes sepsis-causing endotoxin from the bloodstream. A total of 450 patients were treated with either two Toraymyxin columns or two shams. The study did not achieve its primary endpoint of an absolute reduction in mortality at four weeks. Spectral Medical intends to meet with the FDA to discuss the next step on the regulatory pathway.
The Toraymyxin technology was developed in Japan to restore blood pressure and to correct organ dysfunction by using an antibiotic to detoxify the blood. Once the patient’s blood has been extracted, it is passed through a column to remove endotoxins, which are believed to be a major trigger for sepsis.
The device has been used in Japan and parts of Europe for years but has not been approved for wide use in the U.S. because, in the FDA’s opinion, it has never been tested in trials large enough to prove its effectiveness and safety. The agency did, however, clear the system for “compassionate use” in select hospitals.
Source: Spectral Medical, October 3, 2016