FDA Update: July 2019

Jul 16, 2019

Express Scripts Office of Clinical Evaluation and Policy tracks some recent updates to the drug pipeline.

New Pill Bottle

Approval for Slynd, a Progestin-Only Contraceptive

In a press release dated June 6, 2019, Exeltis USA, Inc. announced that the FDA had approved Slynd™ (drospirenone) tablets on May 23, 2019. Slynd is an oral contraceptive that contains only a progestin. Because it does not include estrogen, it is less likely to cause blood clots. Therefore, Slynd may be a safer alternative to contraceptives that contain both estrogen and a progestin for older women, those who smoke and women who are obese. It should not be used by women who have adrenal, kidney or liver diseases because it may raise blood levels of potassium. Exeltis plans a launch in the fall. It will be packaged in cartons of one, three or six 28-day blister cards. Each blister card contains 24 active tablets and four inactive ones For full prescribing information, please go here.

New Indication for Emgality

Eli Lilly’s Emgality® (galcanezumab-gnlm) received a new indication -- to treat adults who have episodic cluster headaches – from the FDA on June 4, 2019. Initially approved in September 2018 to prevent migraine headaches, Emgality belongs to a class known as calcitonin gene-related peptide (CGRP) inhibitors. CGRP is a neuropeptide that promotes vascular changes, inflammation and pain transmission. Blocking it helps prevent or lessen the vasoconstriction that often triggers headaches. In contrast to migraines, cluster headaches occur multiple times a day for relatively short periods (usually lasting for 15 minutes to three hours). Frequently beginning with sudden intense pain that wakes up the patient, they recur daily -- typically for cycles (episodes) that last between three weeks and 12 weeks, but possibly persist for up to a year, and then disappear (remit) for various amounts of time. Chronic cluster headaches do not remit. About 25,000 U.S. patients experience the episodic cluster form; many in roughly predictable cycles. In a clinical trial comparing Emgality to placebo, 71.4% of patients using Emgality had one-half or fewer weekly headache attacks versus 52.6% of patients using the placebo. Patients in both groups averaged about 17.5 weekly attacks at the beginning of the study. At week three, the number was reduced by an average of 8.7 attacks in the actively treated patients and by 5.2 in the group using placebo. Given by subcutaneous (SC) injections, Emgality currently is available as 120mg self-injectors and 100mg and 120mg prefilled syringes. For treating episodic cluster headaches, the dose is 300mg (three successive 100mg injections at the same time) at the start of the cluster cycle and then 300mg once each month until the cycle ends. Emgality’s full prescribing information is here.

Self-Injectors Approved for Nucala

On June 6, 2019, the FDA approved two new dosage forms for Nucala®. Nucala is a humanized interleukin-5 (IL-5) antagonist monoclonal antibody indicated as adjunct maintenance for treat patients at least 12 years old who have severe eosinophilic asthma. It also is approved for adults who have the rare condition, eosinophilic granulomatosis with polyangiitis (EGPA). Given as a monthly SC injection, it previously had to be administered by a health professional in a healthcare setting. The new forms, prefilled syringes and prefilled auto-injectors, each containing 100mg of Nucala, will allow for at-home dosing by the patient or a caregiver. An exact release date is unclear, but GlaxoSmithKline believes the new dose forms will be available soon. Prescribing information is available here.

FDA Expands Approval for Emflaza

A little over two years ago, Emflaza® (deflazacort – PTC Therapeutics) was FDA approved as the only specific treatment of Duchenne muscular dystrophy (DMD) for patients age five and older. The FDA extended its use on June 7, 2019, to patients as young as two years old. Emflaza is an oral corticosteroid that decreases both immune and inflammatory activity to relieve symptoms of DMD and also to delay disease progression. It is dosed by weight at 0.9mg/kg/day as either tablets (which can be crushed and mixed with applesauce for administration) or oral suspension. DMD is very rare — only about 400 to 600 new cases are diagnosed in the United States each year. A condition almost exclusively affecting males, it causes progressive muscle weakening that usually leads to paralysis during the teen years and death in early adulthood. Updated prescribing information is here.

Polivy Approved to Treat Diffuse Large B-Cell Lymphoma

Polivy (polatuzumab vedotin-piiq), an antibody-drug conjugate from Genentech, received approval from the  FDA on June 10, 2019. It is an immunotherapy to be used as part of a regimen, which also includes the chemotherapy (chemo) drugs bendamustine and Rituxan® (rituximab – Genentech/Biogen). Together, they will treat diffuse large B-cell lymphoma (DLBCL) that has recurred or become resistant to therapy for adult patients who have been treated with two or more prior therapies. Polivy is the first FDA-approved drug with an antibody that sticks to CD79b, a protein released only by B-cells. Its drug component then causes the B-cells to disintegrate. Recommended dosing depends on the patient’s weight – 1.8mg/Kg once every 21 days for six cycles given as an intravenous (IV) infusion. Complete prescribing information is here.

Another Herceptin Biosimilar FDA Approved

Kanjinti (trastuzumab-anns – Amgen/Allergan), a biosimilar to Genentech’s Herceptin® (trastuzumab) was FDA approved on June 13, 2019. Given IV, it is indicated to treat breast cancer, metastatic gastric cancers and gastroesophageal junction adenocarcinomas that are positive for epidermal growth factor receptor-2 (HER2+). Dosing varies according to the condition being treated. All trastuzumab products have boxed warnings that they may cause birth defects, heart failure, respiratory distress or severe allergic reactions. Although its launch and pricing plans have not yet been determined, Kanjinti will compete with four other FDA-approved biosimilars for Herceptin – Herzuma® (trastuzumab-pkrb – Celltrion/Teva), Ogivri® (trastuzumab-dkst – Mylan/Biocon), Ontruzant® (trastuzumab-dttb – Samsung Bioepsis).

Pediatric Indication for Victoza Approved

On June 17, 2019, the FDA awarded Novo Nordisk’s Victoza® (liraglutide) a new indication. In combination with dietary changes and exercise, it has been available for nearly a decade to improve glycemic control for adults who have type 2 diabetes. Now, it is approved to treat type 2 diabetes for children as young as 10 years old. A glucagon-like peptide-1 (GLP-1) analog, it lowers blood glucose by stimulating insulin release from the pancreas when blood glucose levels are high. Recommended initial dosing for all patients is 0.6mg once a day delivered SC through a pre-filled, multi-dose pen-like device. If blood sugar is not controlled adequately after one week, the dose may be increased to 1.2mg/day for at least one week before increasing to a maximum daily dose of 1.8mg. Victoza’s prescribing information included a boxed warning about an increased risk of some types of thyroid tumors. It also warns against its use by patients or close relatives of patients who have medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2). Its full prescribing information, which includes a Medication Guide for patients, is here.

Botox Receives Pediatric Indication

Allergan’s Botox® (onabotulinumtoxinA) was FDA approved on June 20, 2019, to treat patients who are between two years old and 17 years old and who have upper limb spasticity (contractions of the muscles in the hands, wrist and elbow). Cerebral palsy, head injuries, multiple sclerosis (MS), spinal cord injuries or stroke and cause muscle spasms in the limbs. Symptoms may include cramping, pain, shaking or stiffness in the joints of the arms and hands. Botox is a neuromuscular blocker that has been on the market for 30 years. In addition to several cosmetic uses, it has numerous medical indications including bladder dysfunction, blepharospasm (eyelid contractions), cervical dystonia (neck muscle spasms that cause head tilting), chronic migraine, severe axillary hyperhidrosis (excessive underarm sweating) and strabismus (crossed eyes). For treating upper limb spasticity, recommended pediatric dosing depends on the weight of the patient, the affected muscles and the severity of spasticity. Doses are divided into smaller units and SC injections are given into two or more sites in the affected muscles. For each treatment, doses should not exceed the lesser of six units/Kg or 200 Units. Injections should be given at intervals of at least 12 weeks. All botulinum toxin products, including Botox, carry a boxed warning that they may migrate away from the areas where they are injected and possibly cause widespread side effects, such as serious breathing or swallowing problems. Migration and side effects can happen even several months after the product has been injected. Full prescribing information and a patient Medication Guide for Botox are available here.

Vyleesi Approved for Female Sexual Desire Disorder

AMAG Pharmaceuticals received approval from the FDA on June 21, 2019, for Vyleesi (bremelanotide). It is a first-in-class melanocortin receptor agonist for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD). It is not intended to treat postmenopausal women or those who have medical or psychiatric conditions, relationship problems or medication use that could interfere with sexual desire. Vyleesi will be available in cartons containing four single-dose auto-injectors to be used SC on-demand at least 45 minutes in advance of expected sexual activity. Injections should be limited to one in 24 hours and eight per month. Therapy should be re-evaluated if no improvement is seen after eight weeks of treatment. AMAG plans a launch in September. Pricing has not yet been announced. For complete prescribing information, please go here.

Vertex Gets Pediatric Indication for Symdeko

The FDA announced on June 21, 2019, that — under Priority Review — it has extended the use of Symdeko® (tezacaftor/ivacaftor) to children six years of age and older. First approved in February 2018 as a fixed-dose combination of tezacaftor 100mg/ivacaftor 150mg packaged with separate ivacaftor (Kalydeco®) tablets, it was indicated for patients 12 years of age and older. Symdeko treats cystic fibrosis (CF) for patients who either are homozygous for an F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that responds to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence. Tezacaftor is a CFTR corrector -- it helps to stabilize CFTR proteins at the correct places for ion channels on cell surfaces. Ivacaftor potentiates CFTR to help keep the ion channels functional, which increases the flow of water and salts into and out of cells. Recommended dosing is one combination tablet in the morning along with a high-fat food and then one ivacaftor tablet about 12 hours later. Additionally, the FDA approved a lower strength combination tablet, tezacaftor 50mg/ivacaftor 75mg that will be used along with a second ivacaftor tablet, 75mg, for patients who weigh 30Kg (about 66 pounds) or less. Complete prescribing information is here.

Sunosi Scheduled

The U.S. Drug Enforcement Agency (DEA) has placed Sunosi (solriamfetol – Jazz Pharmaceuticals) into Schedule IV (C-IV) of the Controlled Substances Act. FDA approved in March, Sunosi is the first in its class — dual-acting dopamine and norepinephrine reuptake inhibitors (DNRI). It is indicated to improve wakefulness for adults who have extreme daytime sleepiness related to narcolepsy or obstructive sleep apnea (OSA). A C-IV designation indicates that Sunosi may be misused, but the possibilities of abuse and dependence are small. It will be launched early in July as oral tablets with recommended initial dosing of 75mg/day for narcolepsy and 37.5mg/day for OSA. The maximum dose is 150mg/day. Sunosi will be excluded at launch on the Express Scripts National Preferred Formulary (NPF) until our formulary development process is complete. Full prescribing information with a patient Medication Guide is here.

DA Approval Extended for Doptelet

Doptelet® (avatrombopag) tablets received a new indication on June 26, 2019. Originally, it was FDA approved in May 2018, only for the short-term, pre-procedure treatment of thrombocytopenia (platelet counts lower than 50,000mcg/Liter of blood) for adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure. Now it has an additional indication for treating adults who have chronic immune thrombocytopenia (ITP) that is unresponsive to previous treatment. About 60,000 American adults have ITP, an autoimmune condition that increases the risk of bruising and bleeding due to low platelet counts. Doptelet is a thrombopoietin receptor agonist that increases the production of platelets, so taking it may increase the chance of having blood clots. To treat ITP, the recommended initial dose is 20mg once a day with food. Doses and dose schedules can be changed to maintain a more normal platelet count; but no more than 40mg should be taken/day. Revised prescribing information is here.

Rhinosinusitis Approval for Dupixent

Dupixent® (dupilumab – Regeneron/Sanofi) was approved for a new indication by the FDA on June 26, 2019. It is the first treatment specifically for adult patients who have chronic rhinosinusitis with nasal polyps. As an interleukin-4 alpha receptor (IL-4Rα) and interleukin-13 (IL-13) blocker, it interferes with the inflammatory process. In the clinical studies that lead to the new indication, nasal congestion decreased for more than one-half of patients treated with Dupixent as compared to fewer than 20% of patients using a placebo. Nasal polyps were reduced for up to one-third of actively treated study participants. Those using placebo, however, averaged a small (4% to 7%) increase in polyps. Additionally, Dupixent helped to improve lung function for a significant percentage of trial participants who also have asthma, which is common among patients who have rhinosinusitis. All patients continued using a steroid nasal spray during the trials, but around 75% of those using Dupixent no longer needed systemic steroids or nasal surgery to control their rhinosinusitis and polyps. Given by SC injection, the recommended dose to treat rhinosinusitis is 300mg once every two weeks. Dupixent also has FDA indications for treating patients age 12 years and older who have resistant eczema, eosinophilic asthma or asthma dependent on oral corticosteroids. Its updated prescribing information is here.

Second Biosimilar Approved for Avastin

Pfizer’s Zirabev (bevacizumab- bvzr) was FDA approved on June 27, 2019, for treating metastatic or recurring cases of cervical cancer, colorectal cancer, glioblastoma, non-squamous non-small cell lung cancer and renal cell carcinoma. It was not approved for three other Avastin® (bevacizumab – Genentech) indications (ovarian, fallopian tube, and primary peritoneal cancer), because they are protected by Orphan Drug Exclusivity (ODE). It is administered by IV infusion at doses and schedules that differ according to the cancer being treated. Another Avastin biosimilar, Mvasi (bevacizumab-awwb – Allergan/Amgen), was FDA approved in September 2017 for the same indications as Zirabev. Although a key Avastin patent expires in July 2019, lawsuits could delay biosimilar launches until 2020 or later. Neither Mvasi nor Zirabev is considered to be a generic and neither is automatically interchangeable with Avastin or each other. According to IMS Health, U.S. sales for Avastin were approximately $3 billion in 2018. For Zirabev’s prescribing information, please go here.

FDA Approves New Indication for Soliris

On June 27, 2019, Alexion Pharmaceuticals received approval from the FDA for Soliris® (eculizumab) to treat patients who have neuromyelitis optica spectrum disorder (NMOSD) that produces antibodies to anti-aquaporin-4 (AQP4). Between 4,000 and 8,000 Americans are estimated to have NMOSD, an autoimmune condition that attacks optic nerves and the spinal cord. It causes eye pain, vision loss, incontinence and paralysis. For many patients, symptoms worsen for unpredictable periods of time and then abate at least partially. In a clinical trial of patients with NMOSD, 98% of the patients using Soliris for 48 weeks did not experience an attack of symptoms, as compared to 63% of patients receiving a placebo. The recommended dose for NMOSD is 900mg (three vials) by IV infusion once a week for four doses, one 1,200mg dose after one more week and then 1,200mg once every two weeks. Soliris also has indications for other rare diseases -- paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and generalized myasthenia gravis (gMG). It is available only through a risk evaluation and mitigation strategy (REMS). Its labeling contains a boxed warning about an increased risk of serious meningococcal infections associated with its use. Patents should be vaccinated against meningitis at least two weeks before beginning treatment with Soliris and they should be monitored for signs of meningococcal infections during therapy. Full prescribing information can be found here.

Darzalex Receives Extended Approval for Multiple Myeloma

Janssen was granted expanded FDA approval on June 27, 2019, for its CD38-directed antibody, Darzalex® (daratumumab) to treat multiple myeloma.  In combination with Revlimid® (lenalidomide – Celgene) and dexamethasone, Darzalex now is indicated as first-line treatment for adult patients who have multiple myeloma and who are not candidates for autologous stem cell transplants. After 48 weeks, the Darzalex combination therapy decreased the risk of death or cancer progression by 44% for patients receiving it in a clinical trial -- as compared to patients using Revlimid, alone. For use with Revlimid, the recommended dosing schedule for Darzalex is as an IV infusion once a week for eight weeks, once every two weeks for eight additional doses and then once every four weeks until it stops working or the patient can no longer tolerate the side effects. Although infusion rates may vary, the recommended dose for all Darzalex indications is 16mg/Kg of the patient’s body weight given in a healthcare facility staffed and equipped to provide emergency treatment if an infusion reaction occurs. As monotherapy and along with other drugs, Darzalex also has several previous indications as second- or third-line multiple myeloma treatment. Its prescribing information is available here.

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