New Drug for COPD Maintenance
In April, the Food and Drug Administration (FDA) approved Duaklir Pressair (aclidinium bromide, formoterol fumarate) for the maintenance treatment of COPD. Duaklir Pressair combines aclidinium bromide, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA). It is intended for twice-daily use with the breath-actuated Pressair inhaler. Prescribing information can be found at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210595lbl.pdf.
New HIV-1 drug
ViiV Healthcare gained U.S. Food and Drug Administration approval for a new HIV-1 drug, Dovato (dolutegravir 50mg/lamivudine 300mg). It includes an integrase strand transfer inhibitor (INSTI) and a nucleoside analogue reverse transcriptase inhibitor (NRTI) to treat patients who have HIV-1 that have not been treated previously. In clinical trials, Dovato was as effective and safe as a three-drug combination commonly used for patients newly diagnosed with HIV-1. Dovato is expected to be available later this month with a wholesale acquisition cost (WAC) of about $27,500 per year. Prescribing information is not yet available.
Janssen’s Balversa™ (erdafitinib) Approved
Janssen’s Balversa™ (erdafitinib) was approved by the FDA in April. It is a first-in-class kinase inhibitor that targets fibroblast growth factor receptors (FGFR). These receptors can prolong cancer cell’s survival and promote their growth. It was approved to treat adults who have locally advanced or metastatic urothelial (bladder) carcinoma that has FGFR2 or FGFR3 mutations and that previously was treated with platinum-based combination chemotherapy (chemo). The recommended starting dose is 8mg orally once a day, increased to 9mg daily if blood phosphate levels stay within acceptable limits. Complete prescribing information is at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
The FDA approved Plenity to aid in weight management for overweight and obese adults, in conjunction with diet and exercise. Plenity, a non-systemic, superabsorbent hydrogel, is intended for use in adults with a body mass index (BMI) of 25–40kg/m2. It is the first prescription product to be approved for use in adults with a BMI as low as 25kg/m2, with or without comorbidities. Initial launch of Plenity is anticipated for the second half of this year with a full commercial launch in 2020. For more information, please visit: https://www.gelesis.com/wp-content/uploads/DEN180060_Physician_IFU_FDA_FINAL_4.9.2019Gelesis.pdf
FDA Approves First Generic to Narcan Nasal Spray
The FDA approved the first generic version of Narcan (naloxone hydrochloride nasal spray. Naloxone is used outside of medical settings for the emergency reversal of opioid-induced respiratory and central nervous system (CNS) depression. Its nasal form comes in single-dose, ready-to-use inhaler devices. For more information, visit www.fda.gov.
Teva launches AB-rated generic to Astellas Pharma’s VESIcare® (solifenacin succinate)
Teva announced the launch of its AB-rated generics to Astellas Pharma’s VESIcare® (solifenacin succinate) tablets, a muscarinic antagonist approved for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. Teva was allowed to launch generics in April 2019 because of a settlement agreement. Other manufacturers can launch their generics in about a month, after the last patent on VESIcare expires.
Duobrii Approved for Plaque Psoriasis
In April, the FDA approved Duobrii halobetasol propionate 0.01% and tazarotene 0.045%) for the topical treatment of plaque psoriasis in adult patients. Duobrii combines halobetasol propionate, a corticosteroid, with tazarotene, a retinoid prodrug, into a lotion formulation. Although both drugs have been available separately for several years, Duobrii is the first to contain both. It’s expected to launch in June with a list price of $825 for 100 gm tube. Full prescribing information is available at: https://www.bauschhealth.com/Portals/25/Pdf/PI/Duobrii-PI.pdf
Mavyret Receives Approval in Pediatric Patients
In May, the Food and Drug Administration approved Mavyret for the treatment of all 6 genotypes of hepatitis C virus (HCV) in children 12 to 17 years old or weighing at least 45kg. Mavyret is available as 100mg/40mg fixed-dose tablets in a 4-week (monthly) or 8-week carton. Each carton contains 7 daily dose wallets. No dosage adjustment is required in pediatric patients ≥12 years old or weighing ≥45kg. Full prescribing information can be found at: https://www.rxabbvie.com/pdf/mavyret_pi.pdf
AstraZeneca’s Qternmet XR Approved for Diabetes
The FDA approved the combination drug Qternmet® XR (dapagliflozin/saxagliptin/metformin) for adults who have type 2 diabetes, who currently are taking metformin and who need additional glycemic control despite diet limitations and exercise. Qternmet XR will be taken once a day in the morning along with breakfast or a snack. All medications that contain metformin have a boxed warning that taking it may cause lactic acidosis, the buildup of excessive acid in the blood. Prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210874s000lbl.pdf
The first drugs approved in the U.S. to treat cardiomyopathy
The U.S. Food and Drug Administration approved Vyndaqel® (tafamidis meglumine) capsules and Vyndamax™ (tafamidis) capsules in May. They are the first drugs approved in the U.S. to treat cardiomyopathy (CM) caused by transthyretin-mediated amyloidosis (ATTR), a rare heart condition. Accumulations of malformed proteins (amyloid fibrils) in the hearts of patients who have ATTR-CM cause enlargement and thickening of the heart, which eventually leads to heart failure and death. Tafamidis helps to prevent the formation of amyloid fibrils by stabilizing transthyretin (TTR), a transport protein in blood and cerebrospinal fluid. Recommended daily dosing is 80mg (four capsules) of Vyndaqel or 61mg (one capsule) of Vyndamax, which was developed to increase convenience for patients. The two formulations are not interchangeable, however. Vyndaqel is expected to be launched as soon as possible, and Vyndamax is expected to be available later in 2019. The annual wholesale acquisition cost (WAC) is reported to be $225,000. Prescribing information for both drugs is at: http://labeling.pfizer.com/ShowLabeling.aspx?id=11685.
U.S. Food and Drug Administration approves Vyleesi™
AMAG Pharmaceuticals, Inc. announced in June that the U.S. Food and Drug Administration (FDA) has approved Vyleesi™ (bremelanotide injection), a melanocortin receptor agonist, to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. It is the First FDA-Approved As-Needed treatment for premenopausal women experiencing distress or interpersonal difficulty due to low sexual desire. The Vyleesi autoinjector is the first treatment for this patient population that can be self-administered as needed in anticipation of sexual activity. Full prescribing information is available at https://www.vyleesi.com
Nayzilam Nasal Spray Approved for Seizure Clusters
The FDA approved Nayzilam (midazolam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older. The single-dose spray devices, which contain 5mg of midazolam, are intended for immediate use by caregivers when the unusual seizures start. If a second dose is needed, it should be given in the other nostril about 10 minutes after the first spray. No more than two doses should be used for any one episode, and no more than five seizure clusters should be treated with it in any one month. Nayzilam should not be given more often than every three days. Full prescribing information is available at https://ucb-usa.com/_up/ucb_usa_com_kopie/documents/Nayzilam_PI.pdf
Zolgensma® (onasemnogene abeparvovec-xioi – AveXis) received FDA approval in May. It is a gene therapy that contains a normal copy of the human survival motor neuron 1 (SMN1) gene for patients who have spinal muscular atrophy (SMA) due to bi-allelic mutations in the SMN1 gene. At a dose determined by the patient’s weight, it will be given as one 60-minute intravenous (IV) infusion. A boxed warning on its labeling cautions that Zolgensma may cause damage the liver, so liver function must be monitored before and for three months or longer after treatment. Prescribing information is at: https://www.avexis.com/content/pdf/prescribing_information.pdf
FDA approved Piqray
The U.S. Food and Drug Administration approved Piqray® (alpelisib – Novartis) to be used along with AstraZeneca’s Faslodex® (fulvestrant). Piqray is a kinase inhibitor indicated to treat patients who have advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer that has mutations in phosphoinositide 3-kinase C (PI3KC). The two-drug combination will be second-line therapy when endocrine-based therapy is failing. Piqray’s recommended dose is 300mg (two 150mg tablets) once a day along with Faslodex 500mg intramuscularly (IM) on the first day of each 28-day cycle after one injection each on days 1 and 15 of the first cycle. Qiagen’s therascreen® PIK3CA RGQ PCR companion diagnostic test was approved by the FDA at the same time. Novartis plans an early June launch through open distribution. Full prescribing information for Piqray is available at:
First Generics of Tarceva Launched
Mylan announced the U.S. launch of Erlotinib Hydrochloride Tablets, a generic version of Tarceva. Erlotinib Hydrochloride Tablets is indicated for the treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen. Tarceva tablets have annual sales of $202 million in the U.S., according to IQVIA data as of February 2019.
Second Enbrel Biosimilar Approved
The FDA approved the biosimilar, Eticovo, etanercept-ykro, for the treatment of treat ankylosing spondylitis, plaque psoriasis, polyarticular juvenile idiopathic arthritis (pJIA), psoriatic arthritis (PsA) and rheumatoid arthritis (RA). With this approval, Eticovo becomes the second biosimilar to Enbrel approved for use in the United States, following Erelzi (etanercept-szzs, Sandoz) in 2016 — a product that has yet to launch in the U.S. due to the ongoing legal battle between Amgen and Sandoz. No launch plans have been made yet for Eticovo. For prescribing information, please see: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761066s000lbl.pdf
Additional Indication for Ibrance
The FDA expanded the indication of Ibrance (palbociclib) for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in male patients, in combination with an aromatase inhibitor or fulvestrant. Updated prescribing information can be found at http://labeling.pfizer.com/ShowLabeling.aspx?id=2191
Additional Indication for Keytruda
The Food and Drug Administration approved Keytruda (pembrolizumab) as monotherapy for the first-line treatment of patients with stage III non-small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (tumor proportion score [TPS] ≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. Keytruda, an anti-PD-1 therapy, is already approved to treat various skin, lung, head and neck, urothelial, hematologic, gastro-hepatic, and gynecologic cancers. Updated prescribing information can be found at https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
Additional Approval for Praluent
In April, the FDA approved to reduce the risk of myocardial infarction (MI), stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. Praluent is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor jointly developed by Regeneron and Sanofi. Recommended dosing is 75mg injected subcutaneously (SC) from a prefilled syringe or pen device once every two weeks or 300mg (two consecutive 150mg injections) once every four weeks. Its main competitor, Repatha® (evolocumab – Amgen) was FDA approved on Dec. 1, 2017, for an identical indication. Full prescribing information for Praluent is at: http://products.sanofi.us/praluent/praluent.pdf
New Pediatric Indication for Gattex
In May, Takeda Pharmaceuticals received a new indication for Gattex, a glucagon-like peptide-2 (GLP-2) analog that improves intestinal absorption in patients with short bowel syndrome (SBS) who are dependent on parenteral support. Previously restricted to adult patients, Gattex now can be used for children as young as one year of age. The recommended dose for both adults and pediatric patients is 0.05mg/kg once daily by subcutaneous injection. Gattex has a Risk Evaluation and Mitigation Strategy (REMS) that includes a communication plan to inform healthcare providers and patents about risks of developing cancer and polyps (growths) in the intestine, obstructions in the intestine, gallbladder disease, and biliary tract and pancreatic disease. Prescribing information is at: https://www.shirecontent.com/PI/PDFS/Gattex_USA_ENG.pdf
Labeling Change for Addyi
In April, the FDA issued a safety labeling change order on Addyi. The agency is requiring updates to the Boxed Warning, Contraindication, Warnings and Precautions, and Adverse Reactions sections of the labeling to clarify that women should discontinue drinking at least 2 hours before taking Addyi at bedtime and should not consume alcohol at least until the morning after taking a bedtime dose. In addition, the FDA is requiring that details of the Addyi-alcohol interaction studies be included in the labeling to assist prescribers. Moreover, a Risk Evaluation and Mitigation Strategy (REMS) continues to be necessary to ensure that the benefit of Addyi outweighs the risks of hypotension/syncope with Addyi-alcohol interaction. For more information visit www.FDA.gov.
FDA Eliminates REMS for Truvada® (emtricitabine/tenofovir disoproxil fumarate)
The FDA announced in July that it would eliminate the risk evaluation and mitigation strategy (REMS) for Truvada® (emtricitabine/tenofovir disoproxil fumarate) and its four approved generics for HIV-1 pre-exposure prophylaxis (PrEP). Removal of the REMS means that drug manufacturers are no longer required to provide training materials to healthcare providers and educational information to consumers; safety information will continue to be available via the approved drug labeling and Medication Guide. In 2012, the FDA established the REMS due to the risk of drug resistance with the use of Truvada® for PrEP in undiagnosed early HIV-1 infection. Truvada® is indicated in combination with safer sex practices for PrEP to reduce the risk of sexually acquired HIV-1 in at-risk adults and adolescents weighing at least 35kg. It is also approved for use with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 17kg.
PR001 Gets Fast Track Status for Parkinson Disease with GBA1 Mutation
The FDA has granted Fast Track designation to PR001 for the treatment of Parkinson disease patients with a GBA1 mutation (PD-GBA). PR001 is a potentially disease-modifying, single-dose, AAV9-based gene therapy being developed for the treatment of PD-GBA and neuronopathic Gaucher disease. Parkinson disease with a GBA1 mutation (PD-GBA) is a chronic and progressive neurodegenerative disorder that comprises 7% to 10% of the total Parkinson disease population in the world. A phase 1/2 clinical trial is planned in the second half of 2019 to investigate the safety and tolerability of PR001, key biomarkers, and exploratory efficacy endpoints in patients with PD-GBA.
Empagliflozin Receives FDA Fast Track Designation
The FDA granted Fast track designation to empagliflozin (Jardiance®) for the reduction of the risk of cardiovascular death and hospitalization in patient with chronic heart failure (HF). Empagliflozin, is currently evaluate in two EMPEROR phase III studies include more than 8,500 people with chronic heart failure and are designed to assess the effect of treatment with empagliflozin on cardiovascular death and hospitalization for chronic heart failure as primary endpoints. Empagliflozin (Jardiance®), is a once-daily tablet used along with diet and exercise to lower blood sugar in adults with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease.
FDA Denies NDA for Edsivo™ (celiprolol)
In June, Acer Therapeutics Inc. announced the FDA denied the company’s New Drug Application (NDA) for Edsivo™ (celiprolol) for the treatment of vascular Ehlers-Danlos syndrome (vEDS) in patients with a confirmed type III collagen (COL3A1) mutation. vEDS is considered the most severe subtype of EDS that often leads to complications such as colonic perforation or arterial rupture. The CRL says Acer will have to conduct an adequate and well-controlled trial to determine whether Edsivo™ (celiprolol) lowers the risk of clinical events in patients with vEDS.