FDA Update: November 2018

Nov 20, 2018

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

New Pill Bottle

Seysara Approved to Treat Acne

On Oct. 1, 2018, Paratek Pharmaceuticals’ Seysara (sarecycline) tablets, a tetracycline-derived antibiotic, was granted FDA approval to treat acne. Specifically, it is indicated for once-daily use to treat inflammatory lesions of non-nodular moderate-to-severe acne vulgaris in patients who are at least nine years old. Recommended dosing is 60mg (for patients who weigh between about 73 pounds and 119 pounds (33kg to 54kg), 100mg for patients between 120 pounds and 185 pounds (55 kg to 84kg) and 150 mg for patients between 186 pounds and 300 pounds (85kg to 136kg). If acne has not lessened after three months of treatment, continued use may not provide additional benefit. Seysara will be marketed in the United States by Almirall, which plans a January 2019 launch. For its full prescribing information, please see here.

New Antibacterial, Nuzyra, Approved

Paratek’s second tetracycline derivative, Nuzyra (omadacycline), was approved by the FDA on Oct. 2, 2018 to treat community-acquired bacterial pneumonia (CABP) and acute skin and skin structure infections (ABSSSI). It is indicated to be used once daily for one week to two weeks -- either infused intravenously (IV) at a dose of 100mg, taken orally at 300mg or a combination of both. If tablets are taken, only water should be consumed for at least four hours before and two hours after oral doses of Nuzyra. Additionally, antacids, dairy products and vitamins should be avoided, or at least separated by four hours or more from oral doses of Nuzyra. It should not be used by pregnant women or children younger than 12 years old. Its prescribing information is available here.

Hemlibra’s Indication Extended

Hemlibra® (emicizumab-kxwh - Genentech) was FDA approved on Oct. 4, 2018, for routine prophylaxis to prevent or reduce bleeding episodes for patients who have hemophilia A without factor VIII inhibitors. It was originally approved in November 2017 for patients with hemophilia A with factor VIII inhibitors. Approximately 16,000 individuals in the U.S. have hemophilia A, a congenital deficiency of coagulation factor VIII. About two-thirds of patients do not have inhibitors, which are antibodies to factor VIII replacements. Hemlibra is a bispecific monoclonal antibody that replaces the activity of factor VIII by sticking to both activated coagulation factor IXa and factor X to prevent bleeding episodes. It is self-administered subcutaneously once a week, once every two weeks or once every four weeks. A boxed warning on its labeling cautions that some patients have experienced thrombotic microangiopathy or thromboembolism (severe blood clots) after using activated prothrombin complex concentrate (rescue treatment) to treat bleeds for 24 hours or more while receiving Hemlibra therapy. The new indication was granted as a Breakthrough Therapy. Its updated prescribing information is located here.

Tegsedi Approved for Hereditary Transthyretin-Mediated Amyloidosis

Ionis Pharmaceuticals received approval from the FDA for Tegsedi (inotersen) on Oct. 5, 2018. It is indicated for the treatment of adults who have polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR). The recommended dose for Tegsedi is 284mg administered as a once-weekly subcutaneous (SC) injection. It decreases the amounts of TTR proteins in the blood by blocking the mutated RNA that produces them. A boxed warning on its labeling cautions that using it may cause thrombocytopenia (possibly sudden and dangerous drops in platelet count) and/or glomerulonephritis (kidney inflammation that may cause kidney failure). Due to its potentially severe side effects, Tegsedi was approved with a risk evaluation and mitigation strategy (REMS). Akcea Therapeutics, a subsidiary of Ionis, will be marketing Tegsedi. Akcea planned to launch Tegsedi single-dose prefilled syringes within one to three weeks. Complete prescribing information is available here.

Revcovi Approved to Treat Adenosine Deaminase Severe Combined Immune Deficiency

On Oct. 5, 2018, the FDA approved Leadiant Biosciences’ Revcovi (elapegademase-lvlr) injection. It is a pegylated recombinant product that replaces adenosine deaminase (ADA), an enzyme that is deficient in patients who have adenosine deaminase severe combined immune deficiency (ADA-SCID). Recommended initial dosing for previously untreated patients is 0.2mg/kg of ideal body weight given by intramuscular (IM) injection twice weekly for a minimum of 12 to 24 weeks until immune reconstitution is achieved. For those changing from a prior enzyme treatment, one dose of 0.2mg/kg is administered once a week. After immune function has been reestablished, doses may be reduced to maintain blood levels of ADA. Revcovi is expected to be launched by the end of 2018. Its full prescribing information is available here.

Indication Extended for Gardasil 9

On Oct. 5, 2018, the FDA approved Merck’s Gardasil® 9 (human papillomavirus 9-valent vaccine, recombinant) for individuals between 27 and 45 years old. It has been available in the U.S. since 2014 for use in patients between nine and 26 years of age. Gardasil 9 provides protection against nine strains of human papilloma virus (HPV), but it does not treat any HPV infection the patient already has. Additionally, Gardasil 9 offers no protection against HPV strains the patient was exposed to before being vaccinated. For adults between the ages of 15 and 45 years old, it is given in a series of three shots over six months. The U.S. Centers for Disease Control and Prevention (CDC) estimates that approximately 14 million Americans are infected with HPV each year. Many individuals are not even aware of the infections and most clear up without treatment. However, some HPV strains may cause genital warts and some may develop into cancers of the anus, cervix, penis, throat or vagina. Prescribing information can be found here.

Xarelto Gains New Indication

Janssen received a new FDA indication for its oral anticoagulant, Xarelto® (rivaroxaban) on Oct. 11, 2018. Taken along with aspirin, Xarelto now is approved to reduce the risk of major cardiovascular (CV) events, such as heart attacks, strokes and CV-related death, for patients who have chronic coronary artery disease (CAD) or peripheral artery disease (PAD). Xarelto has several previous FDA approvals, including to prevent and treat deep vein thromboses (DVT) and pulmonary embolisms (PE). It works by blocking blood clotting factor Xa, thereby reducing the ability of the blood to form clots. In the clinical trial that led to the most recent approval, patients taking 2.5mg of Xarelto twice a day and a once-daily 100mg aspirin experienced 14% fewer heart attacks, 42% fewer strokes and 22% fewer CV deaths than patients taking only aspirin. No increases were seen in bleeding into the brain or fatal bleeding among study participants. Xarelto carries a boxed warning that stopping an anticoagulant abruptly increases the risk of blood clots. Additionally, undergoing a spinal procedure, such as spinal anesthesia or a spinal puncture, while taking Xarelto may cause blood to accumulate in the spine, potentially damaging the spinal cord and leading to impairments in movement. Revised prescribing information for Xarelto is available here.

Generic AndroGel 1.62% Topical Gel Launched

Perrigo announced the launch of its AB-rated generic to AbbVie’s AndroGel® (testosterone) 1.62% topical gel, CIII, on Oct. 16, 2018. It is approved for treating men who have deficiencies or absences of natural (endogenous) testosterone. AndroGel is applied topically once daily in the morning to clean, dry, intact skin of the shoulders and upper arms. Perrigo will receive 180 days of generic exclusivity. While the launch of an authorized generic is expected, additional generics will be delayed until at least April 2019. U.S sales of AndroGel 1.62% accounted for $1 billion for the most recent twelve months ending in August 2018, according to IQVIA.

Talzenna Approved for Breast Cancer

The FDA approved Pfizer’s Talzenna (talazoparib) capsules on Oct. 16, 2018. A poly (ADP-ribose) polymerase (PARP) inhibitor, Talzenna blocks an enzyme cancer cells use to restore their DNA. It is indicated to treat deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2‑negative locally advanced or metastatic breast cancer in adults. Recommended dosing is one mg daily after the genetic mutation has been verified by an FDA-approved diagnostic test, such as BRACAnalysis CDx (Myriad Genetics Laboratories). Pfizer planned to launch Talzenna in October. Complete prescribing information is located here.

Dupixent Approved to Treat Eosinophilic Asthma

Dupixent® (dupilumab) was granted a second indication by the FDA on Oct. 19, 2018. Originally FDA approved in March 2017 to treat atopic dermatitis, Dupixent now also is approved to treat patients who have eosinophilic asthma or who have asthma that is managed only by taking corticosteroids orally. It will be added to their usual maintenance therapy for patients at least 12 years old. Jointly developed by Sanofi and Regeneron, Dupixent is an interleukin-4 alpha receptor (IL-4Rα) blocker  ̶  an antibody that disrupts the inflammatory process. Given as subcutaneous (SC) injections, it can be self-administered or injected by a caregiver. After the first Dupixent dose of 400mg or 600mg (two injections at the same time but at different injection sites), recommended dosing for its asthma indication is either 200mg or 300mg once every two weeks. It is dispensed in pre-filled, single-dose syringes. Revised prescribing information is available here.

Generics Launch for Onfi

Several generic companies launched AB-rated generics for Lundbeck’s Onfi® (clobazam) tablets and Onfi oral suspension after orphan exclusivity for the brand expired on Oct. 21, 2018. A C-IV controlled substance, clobazam is a benzodiazepine that is used with other antiepileptic drugs to manage seizures for patients as young as two years old who have Lennox-Gastaut syndrome (LGS). Affecting up to 24,000 children in the United States, LGS causes different types of seizures. It includes cognitive impairments and a distinctive electroencephalogram (EEG) pattern, as well. Patients with LGS may have frequent injuries from falls associated with “drop” seizures, which cause sudden, unpredictable losses of muscle tone. It is hard to manage -- needing multi-drug therapy that generally is required throughout the patient’s life. Labeling for clobazam carries a boxed warning that taking it at the same time as an opioid could result in extreme sleepiness, breathing problems, coma or even death. As estimated by IQVIA, U.S. sales for Onfi tablets and oral suspension together amounted to around $849 million in the 12-month period that ended on Aug. 31, 2018.

Xofluza Approved to Treat Flu

On Oct. 24, 2018, the FDA approved Genentech and Shionogi and Company’s Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza (flu) in patients 12 years of age and older who have had flu symptoms for no longer than 48 hours. Xofluza blocks influenza cap-dependent endonuclease, an enzyme involved in the replication of the flu virus. Recommended dosing is a single 40mg dose for those weighing 40kg (about 88 pounds) to less than 80kg (about 175 pounds). Patients weighing 80kg or more should receive one dose of 80mg. Genentech plans on making Xofluza available within the coming weeks. Full prescribing information can be found here.

Xyrem Now Indicated for Children

Jazz Pharmaceuticals received a new indication for Xyrem® (sodium oxybate) on Oct. 26, 2018. An oral solution containing 0.5mg/mL, it is taken at bedtime to treat cataplexy (random, sudden loss of muscle strength) due to narcolepsy and excessive daytime sleepiness. Previously restricted to adult patients, Xyrem now can be used for children as young as seven years old. After small starting doses, which are weight-based for children, it must be increased gradually to a recommended daily range of 6mg to 9mg. The total dose is divided into two equal parts that each are diluted with about one-fourth cup of water. Following two hours or more without eating, the first dose is taken as soon as the patient is in bed; and the second between two-and-one-half and five hours later. A C-III controlled substance, Xyrem carries a boxed warning that taking it while drinking alcohol and/or using central nervous system (CNS) depressants (such as antipsychotics, benzodiazepines, opioids or sedating antidepressants) can significantly affect consciousness and also can lead to severe breathing problems. Additionally, it has a Risk Evaluation and Mitigation Strategy (REMS) that requires Xyrem to be prescribed only by certified providers, dispensed only through a single certified specialty pharmacy and sent only to registered patients. Prescribing information is located here.

Bijuva Approved to Treat Menopausal Symptoms

Bijuva (estradiol, 1mg/progesterone, 100mg – TherapeuticsMD) capsules was approved by the FDA on Oct. 28, 2018. It is indicated to be taken once every evening along with food to relieve moderate-to-severe vasomotor symptoms due to menopause for women who have not had hysterectomies. “Bio-identical” hormone replacement has been available from compounding pharmacies and as single-component (estradiol or progesterone) commercial products for decades. However, Bijuva is the first to use them together in an FDA-approved commercial combination. Bio-identical hormones chemically duplicate natural ones to help manage symptoms, which include facial flushing, hot flashes and night sweats. Labeling has a boxed warning, common to all female-hormone replacements, that using an estrogen/progestin combination may raise the risk of blood clots, dementia, breast cancer or strokes. Taking estrogen alone may contribute to developing CV conditions, dementia and endometrial cancer. Hormone replacement should not be used to prevent CV disease or dementia. No cost information currently is available for Bijuva, but its launch is planned for the second quarter of 2019. Complete prescribing information is available here.

Cardiovascular Indication for Invokana

On Oct. 29, 2018, the FDA approved a new indication for Janssen’s Invokana® (canagliflozin) tablets, Invokamet® (canagliflozin/metformin) tablets and Invokamet®  XR (canagliflozin/metformin) extended-release tablets. Invokana is a sodium-glucose co-transporter 2 (SGLT2) inhibitor, first approved in 2013 to treat adults who have type 2 diabetes. It and its metformin combinations now are indicated to decrease the risk of a heart attack, stroke or CV-related death for adults who have both type 2 diabetes and diagnosed CV disease. Although other diabetes drugs, such as Novo Nordisk’s Victoza® (liraglutide) injection, are approved for the same indication, the Invokana line currently includes the only oral drugs to have the indication. All three drugs containing canagliflozin have a boxed warning that taking them may increase the risk of amputation of the toes, feet or legs. Updated prescribing information is here.

Keytruda Gains New Indication

Merck’s Keytruda® (pembrolizumab) injection was granted a new FDA approval on Oct. 30, 2018, as first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC). It will be used along with carboplatin and either paclitaxel or Abraxane® (nab-paclitaxel) and given at an IV dose of 200mg once every three weeks until the cancer begins to progress or until the patient can no longer take the drug. Keytruda is a human programmed death receptor-1 (PD-1)-blocking antibody that has previous indications for treating multiple types of cancer. As an immuno-oncology (I/O) drug, it increases the ability of the body’s immune system to destroy cancer cells. Its new indication does not depend on PD-L1 expression and patients will not need pharmacogenomic testing before it can be used. Complete, revised prescribing information is located here.

Generic Launched for Levitra

Lannett Company released vardenafil, an AB-rated generic for Bayer Healthcare’s Levitra®, to the U.S. market on October 31, 2018. Vardenafil is a phosphodiesterase-5 (PDE-5) inhibitor indicated to treat erectile dysfunction (ED), which is estimated to affect about 18 million American men. According to IQVIA, Levitra’s sales amounted to approximately $127 million in 2017. Other ED drugs, sildenafil (Viagra® - Pfizer) and tadalafil (Cialis® - Eli Lilly), also are available as generics.

MedWatch Update


On Oct. 30, 2018, the FDA announced that irbesartan tablets labeled as Westminster and Golden State Medical Supply were being recalled to the patient level. Trace amounts of a contaminant, N-nitrosodiethylamine (NDEA), a probable human carcinogen, were found in samples of the raw material used to manufacture the tablets by another company, ScieGen Pharmaceuticals. Potential harm to patients is low, so patients who have recalled irbesartan should not stop taking it. They should call their doctors or pharmacies to see if they can switch to an irbesartan product that was not recalled or if they need a prescription for a different drug. For more information on the recall, including a list of affected NDC and lot numbers, the FDA notice is available here.

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