FDA Update: April 2019

Apr 24, 2019

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

New Pill Bottle

Lilly to Market Lower-Priced Insulin Lispro

Eli Lilly announced on March 4, 2019, that it will be releasing Insulin Lispro, a half-priced version of its rapid-acting insulin Humalog® (insulin lispro injection 100 Units/mL). Injected subcutaneously (SC) to treat diabetes, Insulin Lispro is used right before or after a meal to manage glucose spikes from food. It also can be used through an insulin pump. Typically, a longer-acting insulin is used to provide a steady level of insulin that mimics natural insulin production. Insulin Lispro will be launched in the U.S. as soon as distribution agreements are in place. It will be available in 10mL vials at a list price of $137.53 and in packages of five KwikPens at $265.20. Humalog 200 Units/mL currently remains brand-only.

Spravato Approved to Treat Resistant Depression

Janssen’s Spravato (esketamine) CIII nasal spray received approval from the FDA on March 5, 2019. It will be used, along with an oral antidepressant, for adult patients who have major depression that has not been relieved by two or more appropriate length- and dose-rounds of treatment with other antidepressants. Spravato will be available in single-use devices containing 28mg (two sprays). For the first four weeks, it will be dosed twice a week beginning at 56mg (two sprays followed by two more approximately five minutes later) for the first time, and then either 56mg or 84mg for the next seven treatments. For maintenance, the recommendation is either 56mg or 84mg once a week for the next four weeks, and then either dosed once a week or once every two weeks. Spravato will be distributed directly to certified treatment centers that have specially trained providers. Patients will administer Spravato, but they will be supervised by a healthcare professional during each treatment and then monitored for a minimum of two hours after. A boxed warning, a risk evaluation and treatment strategy (REMS) and a patient Medication Guide detail possible sedation, dissociation, suicidal thoughts and misuse associated with using Spravato. Prescribing information is here.

FDA Approves Tecentriq to Treat Triple-Negative Breast Cancer

On March 8, 2019, the FDA granted accelerated approval for Tecentriq® (atezolizumab - Roche), to treat adult patients who have locally advanced or metastatic triple-negative breast cancer (TNBC) that cannot be removed by surgery. The tumors also must express programmed death receptor-ligand 1 (PD-L1), as verified by an FDA-approved diagnostic test. The first immunotherapy drug approved for breast cancer, it helps the body’s immune system attack cancer cells. Tecentriq will be used in combination with a Celgene chemotherapy drug, Abraxane® (paclitaxel protein-bound particles for injectable suspension [albumin-bound]) for its TNBC indication. About 15% of breast cancers are TNBC. That is, they do not have receptors for estrogen and progesterone and they do not produce excessive amounts of human epidermal growth factor receptor-2 (HER2) protein, which makes them resistant to many targeted drugs. TNBC patients tend to be younger than those who have other types of breast cancer. It is aggressive – likely to spread quickly, recur rapidly and average only about 12 months to 15 months in overall survival (OS) time. In the clinical trial that lead to approval, OS was 21.3 months for patients treated with Tecentriq and Abraxane compared to 17.6 months for patients using only Abraxane. Recommended dosing is 840mg given by intravenous (IV) infusion over 60 minutes on the first and 15th days of 28-day cycles. Additional trials will be needed to confirm effectiveness before the FDA grants full approval. Tecentriq’s complete prescribing information may be found here.

Fourth Herceptin Biosimilar Approved

Trazimera™ (trastuzumab-qyyp), Pfizer’s biosimilar to Herceptin® (trastuzumab – Genentech) was FDA approved on March 11, 2019. It has indications for treating breast cancer, metastatic gastric cancers and gastroesophageal junction adenocarcinomas that over-produce 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 Pfizer has not announced launch or pricing plans, Trazimera will compete with three other Herceptin biosimilars – Herzuma® (trastuzumab-pkrb – Celltrion/Teva), Ogivri® (trastuzumab-dkst – Mylan/Biocon) and Ontruzant® (trastuzumab-dttb – Samsung Bioepsis) -- that the FDA approved previously, but that have not yet been launched. None of the biosimilars is interchangeable with Herceptin or any of its other biosimilars. IQVIA estimated Herceptin’s 2018 sales in the U.S. at about $2.9 billion. Full prescribing information for Trazimera is here.

New Indication for Dupixent

The FDA approved an additional pediatric indication for Dupixent® (dupilumab) on March 11, 2019. Already indicated to treat adolescents and adults who have eosinophilic asthma and adults who have moderate-to-severe atopic dermatitis (eczema), it now also can be used for treating patients as young as 12 years old who have moderate-to-severe atopic dermatitis that has not responded to prior therapies. Atopic dermatitis is a chronic inflammatory disease that results in cracked, dry, itchy and/or oozing skin. Jointly developed by Sanofi Genzyme and Regeneron, Dupixent is an interleukin-4 alpha receptor (IL-4Rα) inhibitor that interrupts the inflammatory process. Given as SC injections, it can be self-administered or injected by a caregiver. For preteen and teen-aged patients who weigh less than 60Kg (about 130 pounds) the recommended starting dose is 400mg followed by 200mg once every two weeks. The adult dose of a 600mg loading dose and then 300mg every other week is recommended for pediatric patients who weigh 60Kg or more. For Dupixent’s complete prescribing information, please see here.

Rocklatan Approved to Treat Glaucoma

Aerie Pharmaceuticals received approval from the FDA on March 12, 2019, for a new combination eye drop to treat open-angle glaucoma and ocular hypertension. Rocklatan™ (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005% combines the only presently FDA-approved Rho kinase (ROCK) inhibitor -- Aerie’s Rhopressa® (netarsudil ophthalmic solution) 0.02% -- with a prostaglandin analog. Rhopressa increases filtration of fluid from the eyes through the trabecular mesh, which is small areas of spongy tissue in the front of the eyes. It drains fluids from the eyes into small blood vessels. Rhopressa also may decrease the production of fluid inside the eye and/or prevent fiber buildup in the trabecular regions. The prostaglandin, latanoprost, also promotes fluid drainage, but through a different pathway. Recommended daily dosing is one drop in each eye. A second-quarter 2019 launch is being planned. Analysts expect the wholesale acquisition price (WAC) to be slightly higher than Rhopressa’s WAC of $100 per bottle containing 2.5mL of solution (approximately 50 drops). Complete prescribing information for Rocklatan is available here.

New Valsartan Generic Approved

Under a streamlined review process, the FDA approved Alkem Laboratories’ generic angiotensin receptor blocker (ARB), valsartan, on March 12, 2019. ARBs are used widely to treat high blood pressure and heart disease. Although generic valsartan has been available in the U.S. since 2014, multiple manufacturers recently have had to recall much of it and other generic ARBs due to potentially cancer-causing nitrosamine impurities. The contaminants were introduced when the raw material suppliers changed their refining processes. The FDA collaborated with Alkem to assure that different, safer production methods are used for the new generic. Working with additional manufacturers, as well, the FDA plans to approve more new uncontaminated ARB generics so that the current shortage of them is resolved as quickly as possible.

Zulresso Approved to Treat Postpartum Depression

On March 19, 2019, the FDA approved Zulresso (brexanolone – Sage Therapeutics) injection for infusion, the first drug specifically indicated to treat postpartum depression (PPD). It is a neuroactive steroid gamma-aminobutyric acid (GABA)A receptor positive modulator that partially stimulates GABAA receptors in the brain. Zulresso will be given by trained healthcare providers in registered healthcare facilities as an IV infusion over 60 hours at varying dosage rates. Due to the risks of extreme sleepiness and lost or altered consciousness during the infusion, Zulresso has both a boxed warning and a risk evaluation and mitigation strategy (REMS). Patients, who must be enrolled in the REMS before receiving treatment, need continual monitoring during the entire infusion. Full antidepressive effects of Zulresso begin within a few days, however, as compared with the several weeks needed for most oral antidepressants to reach their peak effectiveness. Launch, which is contingent on the timeline for scheduling as a controlled substance by the U.S. Drug Enforcement Agency (DEA), is planned for late in June. Available only through hospitals and clinics; it was approved through the FDA’s Breakthrough Therapy and Priority Review pathways. For full prescribing information, please click here.

Sunosi Approved to Treat Excessive Daytime Sleepiness

The FDA approved Jazz Pharmaceuticals’ Sunosi (solriamfetol) on March 20, 2019. The drug, known as a dual-acting dopamine and norepinephrine reuptake inhibitor, is indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA). The recommended starting dose, which is taken once-daily upon awakening, is 75mg for patients with narcolepsy and 37.5mg for patients with OSA. The dose may be increased every three days to a maximum dose of 150mg once daily. Launch, which depends on the timeline for scheduling as a controlled substance by the DEA, is expected in June. Complete prescribing information is here.

Teva Introduces Exjade Generic

Generics for Novartis’ Exjade® (deferasirox) tablets for oral suspension, were introduced to the U.S. market by Teva on March 22, 2019. Available as 125mg, 250mg and 500mg strengths, they are dissolved in water or fruit juice to drink once a day. Deferasirox treats chronically high blood levels of iron resulting from blood transfusions for patients at least two years old and for patients age 10 years and older who have non-transfusion-dependent thalassemia (NTDT). Doses may be adjusted frequently according to the patient’s weight and kidney function. A boxed warning about its potential to damage the gastrointestinal (GI) system, kidneys and/or liver is required on the labeling for deferasirox. Monthly laboratory tests also are necessary to monitor organ function. Pricing is not known at this time. For 2018, IQVIA estimated that Exjade sales in the U.S. amounted to approximately $134 million.

Generic Launched for Remodulin

Treprostinil, the first generic for Remodulin® injection (United Therapeutics) was launched by Sandoz on March 25, 2019. It decreases exercise-induced symptoms, including shortness of breath, chest pain and fatigue, for patients who have World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH). The National Organization for Rare Diseases (NORD) estimates that about 500 to 1,000 new cases of PAH are diagnosed annually for Americans -- mostly for women between 30 and 60 years old. All of its causes are not yet understood, but up to one-fifth of cases are inherited. Others may be caused by exposure to certain drugs or toxins; as many as one-third are associated with other conditions, particularly connective tissue diseases, such as scleroderma. PAH is a progressive disease that causes high blood pressure in the lungs when the arteries in the lungs stiffen and narrow. The right ventricle of the heart, which has to exert more force to push blood through the lungs, becomes enlarged and, if PAH is not treated, the right part of the heart eventually fails. One of the prostaglandins indicated to treat PAH, treprostinil is given by continuous IV or SC infusion at doses based on the patient’s weight. Sandoz has 180 days of exclusivity. For 2018, United Therapeutics reported $599 million in global sales for Remodulin, which has several additional dosage forms that remain brand only.

New New Multiple Sclerosis Drug, Mayzent, Approved

Novartis received FDA approval on March 26, 2019, for Mayzent® (siponimod) tablets. It slows down disease progression for adult patients who have relapsing forms of multiple sclerosis (MS), including secondary progressive multiple sclerosis (SPMS) with active disease, relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS). The first drug with a specific indication for SPMS, it reduces inflammation and stimulates remyelination in the central nervous system (CNS). Recommended maintenance dosing for most patients is 2mg daily after gradual dose increases starting at 0.25mg on the first day and reaching 1.25mg on day five. Some patients will be maintained on 1mg/day. Complete prescribing information is here.

FDA Approval for New Oral Testosterone Product

The FDA approved Clarus Therapeutics’ Jatenzo® (testosterone undecanoate) capsules on March 27, 2019. It is indicated to treat patients who have male hypogonadism (low testosterone blood levels) caused by genetic conditions, such as Klinefelter syndrome, and structural problems, such as damage from chemotherapy, injuries or radiation. It is not approved to treat age-related low testosterone levels. Jatenzo is a C-III controlled substance and it has a boxed warning that it may increase blood pressure. Patients should be assessed for risk of heart attacks, strokes and other cardiovascular adverse events before beginning treatment and then monitored regularly during therapy. Recommended dosing ranges from 158mg taken twice a day to 396mg twice daily, varying with testosterone blood levels. It will be available in soft-gel capsules containing 158mg, 198mg or 237mg. Cost and launch plans have not been announced. Its full prescribing information is here.

Cimzia Gains New Indication

UCB Pharmaceuticals’ Cimzia® (certolizumab pegol) injection was FDA approved on March 28, 2019, as the first drug specifically indicated to treat non-radiographic axial spondyloarthritis (nr-axSpA), with objective signs of inflammation. The Spondylitis Association of America estimates that about 2.7 million Americans have axial spondyloarthritis (axSpA), an inflammatory arthritis of the spine that usually is recognized in the late teens to mid forties for patients who have chronic, severe back pain. Up to 35% of those patients have nr-axSpA, which does not show in x-rays, making it difficult to diagnose. All forms of axSpA are painful and progressive. Eventually, they can deform and/or fuse the spine. After its original 2008 U.S. approval for adult patients with Crohn’s disease, Cimzia has gained additional FDA approvals for ankylosing spondylitis (AS), psoriasis, psoriatic arthritis (PsA) and rheumatoid arthritis (RA). It is given by SC injection at two-week or four-week intervals. All drugs in its class -- tumor necrosis factor (TNF) inhibitors -- carry a boxed warning that using them may raise the risk of serious infections, including tuberculosis. If used by children, the risk of lymphoma and other cancers may go up, as well. A Medication Guide that accompanies every Cimzia prescription outlines its potential risks for patients. Updated prescribing information is posted here.

Generics Approved for Letairis

Four companies received FDA approval on March 28, 2019, for generic versions of Letairis® (ambrisentan- Gilead) tablets. Indicated to treat pulmonary arterial hypertension (PAH), ambrisentan is an endothelin receptor antagonist that is taken at a recommended dose of no more than 10mg once a day. It originally was approved by the FDA in 2007 with a risk evaluation and mitigation strategy (REMS), because it may damage the liver and/or cause birth defects. PAH is a rare, aggressive and life-shortening vascular disease that is diagnosed for 500 to 1,000 Americans per year. Resulting from excessively high pressure in the blood vessels leading from the heart into the lungs, it worsens progressively. Up to 20% of patients have a genetic form of PAH, but most cases occur spontaneously. Branded Letairis and the generics from Mylan Pharmaceuticals, Sun Pharma and Watson Laboratories will be dispensed under the original REMS (now called Ambrisentan REMS) by specialty pharmacies. The generic made by Zydus Pharmaceuticals was approved with a “parallel” REMS (PS-Ambrisentan REMS) that allows for retail dispensing. Patients must be enrolled in both REMS programs to receive a generic prescription. In 2018, U.S. sales for Letairis amounted to $943 million.

Mavenclad Approved to Treat Multiple Sclerosis

Mavenclad® tablets, a new formulation of cladribine, was FDA approved on March 29, 2019, to treat adults who have MS and who have not been helped by or cannot tolerate other drugs that treat it. Developed by EMD Serono, it can be used to treat relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS), but not for MS with clinically isolated syndrome. Dosing is based on the patient’s weight, with a minimum of 40kg (88 pounds). It is taken in two courses that each include two cycles. For each cycle, the patient takes 10mg or 20mg of Mavenclad once a day for four or five days. After 23 to 27 days, the cycle is repeated until a total dose of 1.75mg/kg is reached for the course. The patient then takes a break of 43 weeks or longer before repeating the two cycles and bringing the total dose to 3.5mg/kg. Further therapy with Mavenclad is not recommended. Tablets should be swallowed whole at least three hours before or after any other oral medications. They should be taken immediately after removal from the blister card and patients should wash their hands carefully after touching them. A boxed warning and patient Medication Guide caution about its possibly serious risks of causing cancers or birth defects. Launch was planned for April 5, 2019, or earlier, but no pricing plans were released. Prescribing information is available here.

Duaklir Pressair Receives FDA Approval

A new breath-actuated, dry-powder inhaler to treat chronic obstructive pulmonary disease (COPD) was approved by the FDA on March 29, 2019. Duaklir® Pressair® (Circassia Pharmaceuticals) contains aclidinium, a long-acting muscarinic antagonist (LAMA) and formoterol, a long-acting beta2-adrenergic agonist (LABA). Directions are to use one inhalation (400mcg of aclidinium and 12mcg of formoterol) each morning and each evening as maintenance therapy. It will be launched in the U.S. during the second half of 2019. Pricing is not yet available.For prescribing information, please see here.

Approval for Avaclyr Ophthalmic Ointment

Avaclyr™ (acyclovir ophthalmic ointment) 3% was FDA approved on March 29, 2019, as both a new drug and an orphan drug. It is an antiviral indicated to treat acute herpetic keratitis (corneal infections caused by Herpes simplex virus). A thin strip about one cm (approximately one-third of an inch) long will be placed in the pocket underneath  the eye five times a day until the infection clears, and then three times a day for one additional week. The manufacturer, Fera Pharmaceuticals, will announce launch and pricing details after it finds a partner company to market Avaclyr. Prescribing information can be found here.

Wider Use Approved for Zelnorm

Zelnorm (tegaserod – Sloan Pharma), which has been restricted to very limited prescribing on the U.S. market, was granted FDA approval for broader use on March 29, 2019. Its availability was severely reduced in 2007 when concerns were raised about its potentially serious cardiovascular risks. After analyzing information from clinical trials and real-world use, the FDA determined that Zelnorm is safe for certain patients to use. Its indication still is narrow, though; for treating irritable bowel syndrome with constipation (IBS-C) only for women who are younger than 65 years old and who have not had gallbladder disease, a heart attack, kidney disease, a stroke or one of several intestinal conditions. Its recommended dose is one 6mg tablet twice daily one-half hour before a meal. If symptoms are not relieved after six weeks, treatment should be stopped. Zelnorm is the only selective serotonin-4 (5-HT4) receptor agonist with an indication for IBS-C. It works differently from other IBS-C medications to promote contraction and relaxation, increase secretions and reduce sensitivity in the GI tract – helping to relieve GI discomfort and normalize bowel movements. Prescribing information is located here.

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