FDA Update: December 2019
Talicia Receives FDA Approval
A new combination product, Talicia® (omeprazole magnesium 10mg/amoxicillin 250mg/rifabutin 12.5mg) delayed-release capsules, was approved by the FDA on Nov. 1, 2019. Containing a proton-pump inhibitor (PPI) and two antibacterial drugs, it is indicated for the short-term treatment of adults who have Helicobacter pylori (H. pylori) infections. Although several similar combination drugs are available, Talicia is the first to contain rifabutin, an antimycobacterial drug more frequently used to treat tuberculosis (TB). By including rifabutin in Talicia, the manufacturer, Redhill Biopharma, hopes to reduce the spread of bacterial resistance, which is increasing to more commonly used antibiotics. H. pylori bacteria are strongly associated with peptic ulcers and some forms of stomach cancer. An estimated 2.5 million American adults are treated for H. pylori-related conditions, each year. After a planned launch in the first quarter of 2020, Talicia will be dispensed in bottles of 84 capsules or cartons of 168 capsules with recommended dosing of four capsules taken together at the same time once every eight hours for 14 days. Patients should not take it while they are taking the antifungal drug, voriconazole, or certain drugs used to treat HIV infections. Because it was approved as an FDA Qualified Infectious Disease Product (QIDP) -- an antibacterial or antifungal drug that treats serious or life-threatening infections with limited patient populations, Talicia will have extended exclusivity before it faces potential generic competition. Its full prescribing information can be found here.
Ziextenzo, a Third Biosimilar to Neulasta, Wins Approval
The Sandoz division of Novartis received FDA approval on Nov. 4, 2019, for Ziextenzo™ (pegfilgrastim-bmez) injection. A biosimilar to Amgen’s Neulasta® (pegfilgrastim) injection, it is indicated to reduce the incidence of infection, expressed by febrile neutropenia, for patients who have nonmyeloid cancers, which are being treated with myelosuppressive antineoplastic drugs that are associated with clinically significant febrile neutropenia. Some forms of chemotherapy (chemo) suppress the activity of bone-marrow cells that generate neutrophils, white blood cells that protect against infections. Pegfilgrastim is a PEGylated form of the granulocyte colony-stimulating factor (G-CSF) analog, filgrastim, which causes bone marrow to produce more neutrophils. For adults, it will be given as 6mg subcutaneously (SC) once in each cycle of chemo. Doses for children who weigh less than 45Kg (99 pounds) are based on body weight. Injections should be administered at least 14 days before or 24 hours after chemo. Sandoz expects to introduce Ziextenzo in 6mg prefilled syringes later in 2019. In addition to the brand product, it will compete with other biosimilars -- Fulphila® (pegfilgrastim-jmdb – Mylan/Biocon) and Udenyca® (pegfilgrastim-cbqv – Coherus BioSciences), both already on the U.S. market. None of the biosimilars is interchangeable with Neulasta or with each other, however. Ziextenzo will be added to Express Scripts’ specialty drug list. See Ziextenzo’s prescribing information here.
Reblozyl Approved to Treat Beta Thalassemia-Associated Anemia
The FDA approved Reblozyl® (luspatercept-aamt) on Nov. 8, 2019. The first erythroid maturation agent (EMA) to be approved in the U.S., it is indicated to treat anemia for adult patients who have beta thalassemia and who need regular transfusions of red blood cells (RBCs). The most common in a group of hereditary conditions, beta thalassemia is a result of mutations in hemoglobin beta (HBB) genes. Patients who have a thalassemia cannot make enough hemoglobin (the part of the blood that carries iron) or their hemoglobin is abnormal. As long as a patient’s hemoglobin (Hgb) level is 11Gm/dL or lower, Reblozyl will be given as SC injections once every three weeks at a beginning dose of 1mg/Kg. The dose may be increased to a maximum of 1.25mg/Kg if the need for RBC transfusions does not decrease after two injections. If Hgb is 11.5mg/dL or higher, doses may be delayed. The manufacturers, Celgene and Acceleron Pharma, expect to launch within the week at an estimated wholesale acquisition cost (WAC) of $3,441 for a 25mg vial and $10,324 for each 75mg vial. The FDA approved Reblozyl under Priority Review; and it also has an Orphan Drug designation. Complete prescribing information is available here.
First Rituxan Biosimilar to Launch in the U.S.
Teva and Celltrion have announced that they will introduce Truxima® (rituximab-abbs) injection for intravenous (IV) use to the U.S. market the week of Nov. 11, 2019. The first FDA-approved biosimilar to Genentech’s Rituxan®, Truxima is indicated for use alone or in combination with chemo to treat adult patients who have chronic lymphocytic leukemia (CLL) or some types of CD20-positive, B-Cell non-Hodgkin’s lymphoma (NHL). Rituximab is an infused monoclonal antibody that targets CD20 receptors on cancerous and normal B-cells resulting in their destruction. Due to patent protection, Truxima currently is approved only for Rituxan’s NHL and CLL indications. However, a settlement agreement with Genentech may allow Truxima to be FDA approved in the second quarter of 2020 for treating some of Rituxan’s other indications -- rheumatoid arthritis (RA) and granulomatosis with polyangiitis and microscopic polyangiitis (GPA/MPA). Ruxience™ (rituximab-pvvr), Pfizer’s Rituxan biosimilar, which was FDAapproved on July 23, 2019, is indicated to treat adults who have NHL, CLL and granulomatosis with GPA/MPA. While its launch date still is uncertain, Ruxience is expected to become available early in 2020. Although the three products do not have clinically significant differences in safety, purity or effectiveness, they are not interchangeable. Rituximab products must be given by healthcare providers in facilities that are equipped and staffed to handle severe adverse effects. Doses and timing vary according to the condition being treated and other therapy the patient is receiving. A boxed warning on their labeling lists potentially fatal side effects, including infusion-related reactions, mucocutaneous (skin and mucus membrane) reactions, progressive multifocal leukoencephalopathy (PML) and reactivation of hepatitis B. Truxima’s WAC is $845.55 for a 100mg vial and $4227.75 for a 500mg vial – about 90% of the WAC for Rituxan. Look here for Truxima’s prescribing information.
FDA Approval for a New Antibacterial, Fetroja
Shionogi’s new cephalosporin-class antibiotic, Fetroja® (cefiderocol) for injection, was approved by the FDA on Nov. 14, 2019. It is indicated for adults who have few or no alternatives after other antibiotics have failed to resolve complicated urinary tract infections (cUTIs) caused by susceptible gram-negative bacteria. Fetroja is effective against several bacteria, including some antibiotic-resistant strains of Enterobacter, Escherichia and Pseudomonas. In addition to diffusing into bacterial cells like other antibiotics, Fetroja uses a unique way to enter and attack bacterial cells. It piggybacks onto iron molecules that are needed by bacteria to survive and divide. In the clinical trial that the FDA used to approve Fetroja, infections cleared for about 18% more of the patients who were receiving Fetroja (72.6%) than those using the current standard of care, which is imipenem/cilastatin (54.6%). Recommended dosing is 2gm infused IV over three hours once every eight hours for seven days to 14 days. Fetroja was approved under the FDA’s Fast Track and Priority Review programs. It also is a qualified infectious disease product (QIDP), an FDA designation which promotes the approval of antibacterial and antifungal drugs to treat serious or life-threatening infections that have limited patient populations. Shionogi plans to launch an early 2020 launch. Here is its prescribing information.
FDA Approves Brukinsa to Treat Mantle Cell Lymphoma
On Nov. 14, 2019, FDA approved Brukinsa™ (zanubrutinib - BeiGene) capsules. It is a Bruton’s tyrosine kinase (BTK) inhibitor indicated to treat mantle cell lymphoma (MCL) that has been treated at least once previously for patients who are 18 years of age and older. Diagnosed for approximately 3,300 Americans each year, MCL accounts for 3% to 6% of non-Hodgkin lymphoma (NHL) cases in the United States. Typically, it is aggressive -- by the time it is diagnosed, it usually has spread to the bone marrow and lymph nodes. After diagnosis, the average survival time is only four to five years. The recommended dose for Brukinsa is 320mg per day, taken either as 160mg (two capsules) twice a day or 320mg (four capsules) once daily. Launch is expected in the next few weeks, but cost estimates are not yet available. For Brukinsa’s full prescribing information, look here.
Adakveo Approved for Sickle Cell Disease
The FDA approved Adakveo® (crizanlizumab-tmca - Novartis) on Nov. 15, 2019. It is indicated to treat vaso-occlusive crises (VOCs) for patients 16 years of age and older who have sickle cell disease. Affecting around 100,000 patients in the United States, sickle cell disease is the country’s most common inherited condition. Most patients have African, Hispanic, Mediterranean, Middle Eastern or Southeastern Asian ancestors and most cases are diagnosed through required newborn screenings. A first-in-class P-selectin inhibitor, Adakveo blocks the activity of a cell adhesion protein involved in VOC, keeping blood cells from clumping and helping to maintain blood flow. It will be administered by a healthcare professional as a 30-minute IV infusion at a dose of 5mg/Kg. The first two treatments will be two weeks apart, then one infusion will be given every four weeks. Novartis plans to launch Adakveo in the coming weeks at a WAC of $2,357 per vial. Here is its full prescribing information.
Abrilada, a Biosimilar for Humira, Wins Approval
Pfizer’s Abrilada™ (adalimumab-afzb), was approved by the FDA on Nov. 15, 2019. The fifth biosimilar to Humira® (adalimumab – AbbVie), it is a tumor necrosis factor (TNF) inhibitor that helps to inhibit inflammation. It is indicated to treat a number of inflammatory conditions including ankylosing spondylitis (AS), adult Crohn's disease, juvenile idiopathic arthritis (JIA), plaque psoriasis, psoriatic arthritis (PsA), RA and ulcerative colitis (UC). Generally, it will be given once every other week as an SC injection at doses that vary according to the condition being treated. A boxed warning on the labels of all TNF blockers outlines the increased risks of cancer and serious infections that may be associated with their use. Patients should be screened for tuberculosis (TB) before starting treatment and periodically while therapy continues. Abrilada is not interchangeable with Humira or with the other Humira biosimilars that already are FDA approved - Amjevita™ (adalimumab-atto - Amgen), Cyltezo™ (adalimumab-adbm - Boehringer Ingelheim), Hadlima™ (adalimumab-bwwd – Samsung Bioepis) and Hyrimoz™ (adalimumab-adaz - Sandoz). Under the terms of an agreement with AbbVie, which is similar to settlements with the other Humira biosimilar manufacturers, Pfizer expects to launch Abrilada in 2023. Check here for its complete prescribing information.
First Drug for Hepatic Porphyria FDA Approved
The FDA approved Givlaari™ (givosiran – Alnylam Pharmaceuticals) injection on Nov. 20, 2019. It is indicated to treat adults who have a rare genetic disease, acute hepatic porphyria (AHP). Patients who have the condition are missing or have defects in some of the liver enzymes important in eliminating byproducts of making heme, the iron-rich part of blood that moves oxygen around the body. As a result of the toxins (porphyrins) that accumulate, patients who have AHP experience sudden attacks that often involve intense pain; that may last for several days or weeks; and that can lead to hypertension, neurologic damage, respiratory failure, seizures and even death. Givlaari is a small interfering RNA (siRNA) molecule that reduces the levels of aminolevulinic acid synthase 1 (ALAS1) to decrease the toxins. Recommended dosing for it is 2.5mg/Kg given (SC once every month by a healthcare provider. Injections should be administered in a facility that is equipped and staffed to handle any anaphylactic reactions that may occur. Alnylam expects a launch before the end of 2019 at WAC of $39,000 per vial. Alnylam estimates that roughly 1,700 patients could qualify for treatment with Givlaari. The FDA approved Givlaari, also designated as an Orphan Drug, under both its Breakthrough Therapy and Priority Review programs. Its full prescribing information is here.
Calquence Receives New FDA Indication
Calquence® (acalabrutinib) capsules was given additional FDA approval on Nov. 21, 2019 as treatment for adults who have chronic CLL or small lymphocytic lymphoma (SLL). Originally approved by the FDA in October 2017, Calquence is a next-generation BTK inhibitor that also is indicated as second-line therapy for MCL. For its new indications, it can be used for patients new to treatment and for those who have had previous therapy. Recommended dosing for all three cancers is one capsule (100mg) every 12 hours. For Calquence’s full prescribing information, look here.
The new indications were approved under the FDA’s Project Orbis, an international agreement that allows drug regulatory agencies in Australia, Canada and the U.S. to share information about new drugs and new indications. All three countries approved the new indications for Calquence at the same time. Eventually, the project will include agencies from additional countries. It also aims to standardize the conducting and reporting of clinical trials for cancer drugs so that they can be approved more quickly. More information about Project Orbis may be found on the FDA’s website here.
FDA Approves Xcopri to Treat Epilepsy
On Nov. 21, 2019, SK Life Science, Inc., the U.S. subsidiary of SK Biopharmaceuticals, received FDA approval for Xcopri® (cenobamate) tablets. The drug has at least two actions – it blocks voltage-gated sodium currents and it modulates gamma-aminobutyric acid (GABA) channels to interrupt nerve impulses and decrease the risk of seizures for adults who have partial-onset seizures. Patients taking it will be started on 12.5mg once a day and then gradually increased to a maintenance dose of 200mg once daily. Some patients may need the maximum dose of 400mg/day. Xcopri can be used alone or in combination with other antiepileptic drugs. Dosages may need to be modified, however, when antiepileptics from different classes are taken at the same time. In clinical trials, some patients took doses of Xcopri that rose over six weeks to either 100mg, 200mg or 400mg/day. The doses were maintained for an additional six or 12 weeks. Compared to a 24% decrease among patients taking a placebo, seizure frequency was reduced by 38% for patients taking 100mg and 55% for patients receiving 200mg or 400mg doses of Xcopri. Some actively treated patients were completely seizure free during the maintenance parts of the studies. SK Life Science expects to launch Xcopri in the second quarter of 2020 after the U.S. Drug Enforcement Agency (DEA) determines the controlled substance category for it. Pricing has not yet been disclosed. Here is its prescribing information.
A New Dosage Form for Riluzole FDA Approved
On Nov. 22, 2019, Aquestive Therapeutics received FDA approval for Exservan™ (riluzole). It is an oral-film formulation of the glutamate inhibitor that is used to treat amyotrophic lateral sclerosis (ALS). A progressive neurological disease, ALS destroys the nerves that control muscle movement, eventually leaving patients unable to move. The ALS Association estimates that roughly 16,000 Americans have ALS -- with around 5,000 new cases diagnosed annually. The large majority of cases occur spontaneously with no known genetic link. Although some people who have the disease, such as Dr. Stephen Hawking, live many years; only about 50% of patients survive for three years after diagnosis. Riluzole neither cures ALS nor reduces its symptoms, but it may help to prolong survival time. Riluzole tablets are available generically and as the brand, Rilutek® (Covis Pharma). An oral suspension, Tiglutik™ (ITF Pharma) also is marketed in the U.S. However, as ALS advances, patients lose the ability to swallow. Using patented PharmFilm® technology, Exservan dissolves on the patient’s tongue without the need for water. Recommended dosing is 50mg (one film) allowed to dissolve on the tongue twice each day. Doses should be taken at least one hour before or at least two hours after consuming food, and patients should not chew the film, spit out any part of it or talk while it is dissolving. Because riluzole may damage the liver, patients should be tested for liver enzymes before treatment and periodically while riluzole is being taken. Exservan films will be packaged individually in small packets. A launch date and pricing are not yet available as Aquestive seeks a distribution partner for the U.S. Check here for its complete prescribing information.
Oxbryta Approved to Treat Sickle Cell Disease
Well ahead of the scheduled date, the FDA approved Oxbryta™ (voxelotor – Global Blood Therapeutics) tablets on Nov. 25, 2019. The first in a new drug class (sickle hemoglobin polymerization inhibitors), Oxbryta also is the first drug that treats the cause of sickle cell disease. Causing normally soft, round RBCs to twist into a characteristic crescent or sickle shape, sickle cell disease also makes them less flexible and more sticky than usual. Additionally, sickled cells do not survive as long as regular RBCs and they do not transport oxygen efficiently. The resulting decrease in hemoglobin causes anemia and fatigue. More than one-half of patients who took Oxbryta in a phase III clinical trial had at least a 1Gm/dL rise in hemoglobin levels after 24 weeks. Fewer than 7% of study patients who took placebos achieved the same result. Oxbryta sticks to hemoglobin, attracting more oxygen and stabilizing red blood cells (RBCs). It also may decrease the thickness of blood and the tendency of blood cells to deform (sickle) while increasing RBC flexibility. Recommended dosing for patients age 12 and older is 1,500mg (three tablets) taken once a day. It is not approved for younger patients. It will be distributed at a WAC of $10,417 per month. For some patients, it is likely to be used in combination with other drugs that are approved to treat some complications of sickle cell disease. The FDA awarded Oxbryta Breakthrough Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations. Because it also was granted the FDA’s Accelerated Approval, further testing, including in patients younger than age 12, will need to be completed successfully before full approval is given. Oxbryta’s prescribing information is here.
Pediatric Indication Approved for Toujeo
Sanofi’s Toujeo® (insulin glargine injection) 300 Units/mL, was granted FDA approval on Nov. 27, 2019, to improve glycemic control for children as young as six years old who need insulin to manage diabetes. A once-daily, long-acting basal insulin, it originally was indicated only for patients who are at least 18 years old. Results from a clinical trial that involved more than 450 children and teens who have type 1 diabetes were similar for Toujeo and for Lantus® (insulin glargine injection) 100 Units/mL, also made by Sanofi. Toujeo and Lantus are the same kind of insulin, but it is concentrated in Toujeo to allow for a lower injection volume and a longer duration of action. Its dosing is individualized based on several factors – primarily the patient’s weight. Toujeo should be administered at the same time each day as an SC injection. It is available in prefilled pens that should be used only for a single patient; they should not be shared. For Toujeo’s revised prescribing information, go here.
RediTrex Receives FDA Approval
Cumberland Pharmaceuticals received FDA approval on Nov. 27, 2019, for RediTrex™, an injectable form of methotrexate. It is indicated as second-line treatment for adults who have psoriasis or RA and children who have polyarticular juvenile idiopathic arthritis (pJIA). To be dispensed in boxes of four single-dose, prefilled syringes, it is indicated for once-weekly SC self-injection into the abdomen or thigh. To treat psoriasis, the recommended dose is 10mg to 25mg; for RA, 7.5mg; and for pJIA, 10mg/m2. Methotrexate also is available as an oral solution (Xatmep® – Silvergate Pharmaceuticals), oral tablets (Trexall® – Teva Women’s Health and generics), generic powder for reconstitution to inject and two other auto-injectors (Otrexup™ - Antares Pharmaceuticals) and (Rasuvo™ - Medexus Pharma). RediTrex will be marketed in the same strengths (7.5mg, 10mg, 12.5mg, 15mg. 17.5mg, 20mg, 22.5mg and 25mg) as the other self-injectable brands. A boxed warning on all methotrexate products cautions that it can cause severe side effects in the bone marrow, gastrointestinal (GI) system, kidneys, liver and lungs. Additionally it can trigger hypersensitivity responses, infections or skin reactions. If methotrexate is used during pregnancy, the fetus may be harmed severely. Cumberland has not yet disclosed its launch or pricing plans. Full prescribing information for RediTrex is here.