FDA Update: May 2019

May 22, 2019

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

New Pill Bottle

Mavenclad Approved to Treat Multiple Sclerosis

Mavenclad®, a new formulation of cladribine, was FDA approved on March 29, 2019, to treat adults who have multiple sclerosis (MS) and who have not been helped by or cannot tolerate other drugs for MS. 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 outline its possible serious risks of causing some cancers and caution that its use during pregnancy may be associated birth defects. Prescribing information is available here.

Ibrance Indicated to Treat Breast Cancer in Men

The indication for Ibrance® (palbociclib – Pfizer) was expanded by the FDA on April 4, 2019. It now is specifically indicated, along with an aromatase inhibitor or Faslodex® (fulvestrant), to treat men who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has progressed or metastasized. The American Cancer Society estimates that approximately 2,700 new cases of breast cancer are diagnosed for male patients each year in the United States. Ibrance is a kinase inhibitor that works by blocking cyclin-dependent kinases (CDK4 and CDK6) to limit the growth of cancer cells. Taken on 28-day cycles, its recommended dose is one 125mg capsule taken daily, along with food, on days one through 21 followed by seven days without Ibrance. Doses may be lowered for patients who have serious side effects. Please see prescribing information.

FDA Approval for Dovato as First-Line Treatment of HIV

ViiV Healthcare gained FDA approval for a new HIV-1 drug, Dovato (dolutegravir 50mg/lamivudine 300mg) on April 8, 2019. It includes an integrase strand transfer inhibitor (INSTI) and a nucleoside analogue reverse transcriptase inhibitor (NRTI) to treat patients who have HIV-1 that has 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 was expected to be available in April with a wholesale acquisition cost (WAC) of about $27,500 per year. Full prescribing information is here.

Evenity Approved to Treat Osteoporosis

Evenity (romosozumab-aqqg - Amgen) was approved by the FDA on April 9, 2019. A monoclonal antibody to treat osteoporosis, it is specifically indicated for postmenopausal women who have a high risk for breaking bones. Candidates for its use include women who have had previous fractures, who have multiple risk factors and who have not had success with previous treatments. By blocking sclerostin, a protein that helps to regulate bone metabolism, Evenity promotes bone formation and also slows down bone resorption. It will be given by a healthcare professional once a month as two separate injections (totaling 210mg) into the upper arm, abdomen or thigh. No more than 12 doses should be administered, but patients should continue treatment with another osteoporosis agent after the course of Evenity is finished. Launch was in mid-April. Complete prescribing information is here.


In a Safety Announcement dated April 9, 2019, the FDA reminded providers and users of prescription opioids that abruptly stopping the drugs can cause devastating side effects for patients who have become dependent on them. For those who have been taking opioids chronically, doses should be decreased gradually on a schedule tailored to each patient’s characteristics and needs. The plan also should include emotional support and counseling, if necessary. Patients who have or may have an opioid misuse disorder may need medication-assisted treatment and those with chronic uncontrolled pain may need to consult with a pain specialist for different ways to manage their conditions. The FDA is requiring labels for opioids to include how to reduce or discontinue their use, as well as information about their additional side effects and interactions with other drugs. For more information, please see the full FDA communication.

Keytruda Approval Extended

Merck’s human programmed death receptor-1 (PD-1)-blocking antibody, Keytruda® (pembrolizumab), received expanded FDA approval for some previous indications to treat non-small cell lung cancer (NSCLC) on April 11, 2019. It now is indicated as single, initial therapy for patients not previously treated for metastatic NSCLC or stage III NSCLC that cannot be treated by surgery or definitive chemoradiation. Before using it, all the tumors must be confirmed -- through an FDA-approved diagnostic test -- to express PD-1. Additionally, they must not have genomic aberrations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). For adults, its recommended dose is 200mg given by a 30-minute intravenous (IV) infusion once every three weeks.

On April 19, 2019, it was approved in combination with the tyrosine kinase inhibitor (TKI), Inlyta® (axitinib - Pfizer), as initial therapy to treat advanced renal cell carcinoma (RCC). For its RCC indication, Keytruda will be infused once every three weeks at a dose of 200mg, while 5mg of Inlyta will be taken orally twice every day. In the KEYNOTE-426 trial that lead to the approval, average progression-free survival (PFS) was four months longer for patients treated with Keytruda and Inlyta compared to those taking Sutent® (sunitinib), a current standard treatment for RCC. Because the combination was approved under the FDA’s Accelerated Approval program, additional clinical studies that confirm a clinical benefit are needed before full FDA approval is granted.

Either alone or in combination with other oncology drugs, Keytruda also is indicated for treating numerous other cancer types. Revised prescribing information is available here.

Balversa Approved to Treat Bladder Cancer

Janssen’s Balversa (erdafitinib) tablets was approved by the FDA on April 12, 2019. It is a first-in-class kinase inhibitor that targets fibroblast growth factor receptors (FGFR). These receptors can prolong cancer cells’ 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. Its launch date and price are still to be determined. Balversa’s complete prescribing information is here.

First Generic for Narcan Nasal Spray

On April 19, 2019, the FDA gave its final approval for Teva’s naloxone nasal spray, the first generic to Narcan® Nasal Spray (Adept Pharma). 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. One spray is given immediately before calling for first responders. If the patient does not recover completely or relapses after recovery, additional doses may be administered – in alternate nostrils – once every two to three minutes until medical help arrives. No special training is necessary to use the devices. Other manufacturers have submitted for FDA approval of naloxone generics and they currently are under Priority Review. FDA is trying to tackle opioid misuse on a number of fronts, including possible approval for nonprescription forms of naloxone and requiring that naloxone be dispensed along with opioid prescriptions. Teva has not yet announced its pricing or launch plans.

Generic VESIcare Launched

On April 22, 2019, 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 early because of a settlement agreement. Other manufacturers can launch their generics in about a month, after the last patent on VESIcare expires. Annual U.S. Sales for VESIcare were $955 million for the most recent twelve months ending in Feb. 2019, according to IQVIA data.

Skyrizi Approved to Treat Psoriasis

The FDA approved Skyrizi (risankizumab-rzaa) on April 23, 2019, for treating moderate-to-severe plaque psoriasis in adults eligible for systemic therapy (oral or injection) or phototherapy (ultraviolet light). Jointly developed by AbbVie and Boehringer Ingelheim, Skyrizi is an interleukin-23 (IL-23) inhibitor that blocks inflammatory processes. Recommended dosing is 150mg — administered as two separate subcutaneous (SC) injections at the same time. The second dose is one month later than the first and then doses are spaced at 12-week intervals. Patients and caregivers will be able to inject at home once they have been trained in proper technique by a health professional. Injections should be self-administered only in the abdomen or upper thigh, however. A Medication Guide for patients will be dispensed with each prescription. Launch is expected in early May through open distribution. Complete prescribing information is here.

Second Biosimilar Approved for Enbrel

Eticovo (etanercept-ykro - Samsung Bioepis), was approved by the FDA on April 25, 2019. A biosimilar to Enbrel® (etanercept), it is indicated to treat ankylosing spondylitis, plaque psoriasis, polyarticular juvenile idiopathic arthritis (pJIA), psoriatic arthritis (PsA) and rheumatoid arthritis (RA). In clinical studies comparing the effects of Eticovo and Enbrel for patients with methotrexate-resistant RA, both drugs produced similar response, progression and antidrug antibody rates. All drugs in the TNF inhibitor class, including Eticovo, carry a boxed warning that using them may raise the risk of serious infections, including tuberculosis (TB). If used for children or teens, the possibility of lymphoma and other cancers may go up, as well. No launch plans for Eticovo have been made public. Erelzi (etanercept-szzs - Sandoz) was FDA approved in 2016, but its release to the U.S. market has been delayed by lawsuits from Enbrel’s manufacturer, Amgen. For Eticovo’s complete prescribing information, please see the prescribing information.

FDA Approves Duobrii to Treat Psoriasis

On April 25, 2019, the FDA approved Duobrii from Bausch Health. It is a topical lotion that combines 0.01% of a high-potency corticosteroid (halobetasol) with 0.045% of a retinoid, tazarotene. Although both drugs have been available separately for several years, Duobrii is the first to contain both. Its indication is for treating adults who have plaque psoriasis. Directions are to apply a thin layer of lotion to dry areas of affected skin once a day with a maximum of 50Gm per week. Pregnant women should not use it; the risk of sunburn is increased by its use; and it may contribute to the development of cataracts or glaucoma. A June launch is planned by Bausch’s subsidiary, Ortho Dermatology, at a wholesale acquisition cost (WAC) of $825 for each 100Gm tube. Full prescribing information for Duobrii may be found here.

Generics Approved for Tracleer

On April 26, 2019, the FDA approved AB-rated generics to Actelion’s Tracleer® (bosentan) 62.5mg and 125mg tablets. By blocking two types of endothelin receptors, bosentan reduces constrictions in pulmonary arteries to relieve pulmonary arterial hypertension (PAH) for patients age three and older. Dosing for patients under the age of 12 is based on their body weights. Patients at least 12 years old start with 62.5mg twice a day, increasing to 125mg twice a day after four weeks only for patients who weigh more than 40kg (88 pounds). Bosentan has a boxed warning and a risk evaluation and mitigation strategy (REMS) because using it increases the chances of liver damage and, if used during pregnancy, serious birth defects. None of the manufacturers has released launch or pricing plans. According to a March 2019 IQVIA report, Tracleer’s U.S. sales for the previous 12 months were $84.8 million.

Pediatric Indication for Benlysta

The IV form of Benlysta® (belimumab – GlaxoSmithKline) was approved by the FDA on April 26, 2019, to treat systemic lupus erythematosus (SLE) for children as young as five years old, who are being treated with standard therapy. SLE is an autoimmune disease characterized by inflammation in connective tissues. It can affect numerous organs, including the heart, kidneys and skin. With an estimated incidence of 16,000 cases per year and a prevalence of about 1.5 million in the U.S., SLE is believed to affect between 5,000 and 10,000 American children. It strikes many more women than men and SLE is especially prevalent among non-Caucasians. Symptoms of SLE usually are treated with cyclophosphamide, corticosteroids and immunosuppressants. Benlysta is a monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS), a protein elevated in the blood of patients who have SLE. As a result of inhibiting this protein, B cells cannot survive as long and not as many evolve into plasma cells that attack normal tissues. For pediatric patients, it is given as a one-hour IV infusion at 10mg/kg once every two weeks for three doses, then once every four weeks. Benlysta’s SC form is not approved for patients under the age of 18 years. Its full prescribing information is on the company’s website here.

Praluent Receives Indication for Cardiovascular Protection

Praluent® (alirocumab) was FDA approved on April 26, 2019 for decreasing the risk of heart attacks, strokes and unstable angina requiring hospitalizations for adults who have established cardiovascular (CV) disease. The new indication was based on results of the ODYSSEY OUTCOMES clinical trial, which included nearly 19,000 patients who were taking the highest recommended doses of statins to lower LDL cholesterol. Compared to patients taking their regular drugs plus a placebo, risks for participants who received Praluent averaged 27% lower for stroke, 14% lower for non-fatal heart attack, 39% lower for unstable angina requiring hospitalization and 25% lower for death from any cause. Praluent is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor jointly developed by Regeneron and Sanofi. Recommended dosing for it is 75mg injected 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. Complete, updated prescribing information for Praluent is available here.

Indication Expanded for Kalydeco

On April 29, 2019, Kalydeco® (ivacaftor – Vertex) was approved by the FDA to treat cystic fibrosis (CF) for children as young as six months old. It treats patients who have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that are proven by an FDA-approved diagnostic test to be responsive to ivacaftor treatment. In 2012, Kalydeco was the first medication approved in the U.S. to treat the underlying cause of CF. Later, its indication was extended to children age 12 months and older. It potentiates CFTR to increase the movement of chloride in the body, helping to regulate water and salt in the lungs. Dosing for patients between six months old and six years old varies according to the child’s weight. For administration, packets of powder are mixed with five mL (about one teaspoonful) of soft food or liquid and given orally every 12 hours along with a fat-containing food, such as milk or peanut butter. Current prescribing information may be found here.

FDA Approval for Mavyret to Treat Adolescents

The FDA extended the indication for AbbVie’s Mavyret™ (glecaprevir 100mg/pibrentasvir 40mg) on April 30, 2019, to include patients between the ages of 12 and 18 years. A direct-acting antiviral (DAA), it combines an NS3/4A protease inhibitor specific to hepatitis C virus (HCV) and a NS5A inhibitor. Mavyret is approved as initial treatment for all six genotypes (GT) of HCV for patients who do not have cirrhosis or who have compensated cirrhosis. It also is indicated to treat patients who have HCV GT 1 infection and who previously were treated with either an NS3/4A protease inhibitor or an NS5A inhibitor, but not with both. The recommended dose is three tablets taken together once daily with food. Treatment lasts for eight, 12 or 16 weeks, depending on which other medications the patient has tried and whether or not the patient has compensated cirrhosis. A boxed warning cautions that taking Mavyret may worsen or reactivate hepatitis B (HBV), so all patients should have an HBV test before starting therapy and then regular monitoring should be performed during treatment for signs of HBV. Prescribing information is here.

Eszopiclone, Zaleplon and Zolpidem Warning

On April 30, 2019, the FDA issued a safety communication about some prescription medications for treating insomnia. It is warning patients that taking eszopiclone, zaleplon or zolpidem may increase the chance of unusual behavior while the patient is asleep or not fully awake. These “complex sleep behaviors” can include driving, eating, sleepwalking and talking on the phone. Even though they are uncommon, such side effects can be dangerous. Therefore, the FDA is requiring manufacturers to place a boxed warning about the risks on the labels of all products containing one of the drugs. Patients who previously have exhibited complex sleep behaviors while taking one of the drugs are encouraged not to continue using any of them. All three are available as generics. Eszopiclone and zaleplon also are sold under the brand names of Lunesta® and Sonata®, respectively. Brands for zolpidem include Ambien®/CR, Edluar®, Intermezzo® and ZolpiMist. More information is in the FDA’s full notice.

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