FDA Approved Drugs: October 2020

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

Onureg Approved

On Sept. 1, 2020, the FDA approved Onureg® tablets, an oral formulation of the pyrimidine nucleoside analog, azacitidine. It will be used to treat adults who have acute myeloid leukemia (AML) that is in complete remission — with or without complete blood count recovery — after an initial course of intensive induction chemotherapy (chemo); but who cannot tolerate intensive curative treatment. In addition to blocking the production of DNA and RNA, it is believed to destroy aberrant cells in bone marrow. Overall survival (OS) for patients treated with Onureg in a major clinical study averaged 24.7 months versus 14.8 months for participants who took a placebo. The recommended dose is 300mg each day for the first 14 days of 28-day cycles. Because it can cause nausea and vomiting, patients should take an antinausea drug about one-half hour before each dose during the first two cycles, at least. In injectable form, azacitidine has been FDA approved since 2004 for treating myelodysplastic syndromes. The intravenous (IV) and subcutaneous (SC) formulations are not interchangeable with Onureg, however, because dosing levels and indications are very different. A launch date and pricing have yet to be announced by the Celgene division of Bristol Myers Squibb. Check here for Onureg’s complete prescribing information.

Qdolo FDA Approved

Qdolo (tramadol – Athena Bioscience) oral solution, 5mg/mL was approved on Sept. 1, 2020, by the (FDA. A C-IV controlled substance, it is indicated for treating adults who have severe pain that requires an opioid, but that does not respond to other treatments. To be administered from an oral syringe or other precisely marked device, dosing begins at 25mg/day and increases at three-day intervals to a recommended dose of 50mg four times a day. Total daily doses should be 400mg or less, treatment should be at the lowest effective dose for the shortest period of time and Qdolo should be tapered to a gradual endpoint – not stopped suddenly. All opioids have boxed warnings that they increase the risk of respiratory failure – especially if taken at the same time as other central nervous system (CNS) depressants such as alcohol or drugs in the benzodiazepine class. They also have risks of addiction and misuse. If used during pregnancy, opioids can cause withdrawal symptoms for newborns. Qdolo should not be used for children under the age of 12 years or for patients younger than 18 years who have had a tonsillectomy or adenoidectomy. Like all FDA-approved opioids, Qdolo has a risk evaluation and mitigation strategy (REMS) requiring prescribers, dispensers and patients to be certified for its use. It will be dispensed through open distribution in 16 ounce (473mL) bottles, but price and launch details have not yet been released. Here is prescribing information for Qdolo.

Higher Doses Approved for Trulicity

Based on results from the phase III AWARD-11 clinical trial, the FDA approved two new doses and pen devices with higher doses of Eli Lilly’s Trulicity® (dulaglutide) injection, on Sept. 3, 2020. The long-acting glucagon-like peptide-1 (GLP-1) agonist originally was FDA approved in 2014 to treat type 2 diabetes along with diet and exercise. Earlier in 2020, it got a second indication for reducing the likelihood of cardiovascular (CV) events, including heart attacks and strokes, for adults who have type 2 diabetes and established CV disease or multiple CV risk factors. It is self-administered once-weekly as an SC injection. In the study, once-a-week doses of 3mg and 4.5mg improved both HbA1C and weight compared to the previously recommended 1.5mg/week dose. Dosing will begin at 0.75mg/week and raised to 1.5mg if needed. If additional control is required, doses can be increased to 3mg and then to 4.5mg at one-month intervals. Single-dose, prefilled pen devices containing 3mg or 4.5mg are expected to be launched before the end of September. Cost information is not yet available. All GLP-1 drugs carry a boxed warning that tumors of the thyroid gland (thyroid C-cell tumors) have occurred among laboratory animals treated with some GLP-1 receptor agonists in preclinical studies. However, whether or not humans using them develop thyroid C-cell tumors, such as medullary thyroid carcinoma (MTC), is not yet known. Patients who have MCT, individuals with close family members who have thyroid C-cell tumors and patients who have Multiple Endocrine Neoplasia syndrome type 2 (tumors in more than one gland) should not use Trulicity. For updated directions, please see the prescribing information here.

Gavreto Approved to Treat Non-Small Cell Lung Cancer

The FDA) approved Gavreto (pralsetinib) capsules on Sept. 4, 2020. It is a targeted kinase inhibitor for treating adult patients who have non-small cell lung cancer (NSCLC) that is verified by an FDA-approved diagnostic test to have rearranged during transfection (RET) fusion mutations. According to the American Cancer Society (ACS), NSCLC affects about 192,000 new patients annually in the United States. Up to 2% of patients who have NSCLC are believed to have RET mutations Gavreto is a small molecule drug that selectively blocks overactive RET signals, without changing the activity of other kinases. Once-daily dosing is recommended at 400mg (four capsules) — at least two hours after and one hour before any food intake. In partnership with Genentech, Blueprint Medicines launched Gavreto within the week Cost is not yet available. Presently, Gavreto is under FDA Priority Review, with a Prescription Drug User Fee Act (PDUFA) date of Feb. 28, 2021, for treating advanced or metastatic RET-mutated medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer. Retevmo (selpercatinib) capsules was FDA approved on May 8, 2020, for treating RET+ NSCLC, as well as for the same thyroid cancers currently being evaluated for Gavreto. Complete prescribing information for Gavreto may be found here.

MedWatch Update - Tecentriq Plus Paclitaxel

The FDA issued a safety communication on Sept. 8, 2020, for patients who have triple negative breast cancer (TNBC), their caregivers and the doctors who treat them. Although the combination of Tecentriq® (atezolizumab - Genentech) injection and Abraxane® (paclitaxel protein-bound particles – Bristol Myers Squibb) for injectable suspension is FDA approved for treating adults who have metastatic TNBC that is positive for programmed death-ligand 1 (PD-L1), regular paclitaxel cannot be substituted for Abraxane. In a major clinical trial, patients who received Tecentriq and paclitaxel did no better than patients using Tecentriq and a placebo. Overall survival was shorter for the paclitaxel-treated group than for the placebo group, as well. Further results are under review by the FDA. Patients who have questions about their treatments should discuss alternatives with their physicians. More information is in the FDA’s notice.

Recall - Acella NP Thyroid

On Sept. 17, 2020, Acella Pharmaceuticals announced that it now is recalling two more strengths (15mg and 120mg) of its NP Thyroid® (levothyroxine/liothyronine) tablets that were not recalled in May. The new consumer-level recall is for tablets that tested below the FDA’s specified level of at least 90% active ingredient. Based on complaints it has received, Acella cites a “reasonable risk” of serious adverse events from under doses for pregnant women, newborns, elderly patients and those who have cardiac conditions. For more information, here is the FDA notice.

Recall - Perrigo Albuterol Inhalers

Perrigo Company has recalled all lots of its albuterol inhalers (NDC# 45802-0088-01) after reports that some inhalers clogged – preventing doses from being delivered at all and raising concerns about the accuracy of doses that were dispensed. Production and distribution of the inhalers was stopped well before the Sept. 17, 2020, recall notice. No other generic or brand-name albuterol inhalers have been recalled. To see the Perrigo press release, look here.

MedWatch Update - Benzodiazepine Class

On Sept, 23, 2020, the FDA announced that it is requiring manufacturers of benzodiazepines to update the Boxed Warning, Medication Guide and other sections of the prescribing information. Presently, the descriptions contained within the prescribing information do not provide enough details about the serious risks of damage caused by the inappropriate use of benzodiazepines. In addition, risks increase when benzodiazepines are combined with some other medications, such as opioids, or substances that can be abused, including alcohol. Benzodiazepines are a schedule IV controlled substance class, so -- even when used as prescribed -- they may lead to abuse, misuse, physical dependence or psychological dependence after days or weeks. Suddenly stopping benzodiazepines or reducing the dose too quickly can be life-threatening because of the risk for psychoses, seizures and other severe withdrawal symptoms. Benzodiazepines are widely prescribed to treat anxiety, insomnia, panic disorder, phobias and seizures. The FDA found in post-marketing analyses that benzodiazepines are often taken while alcohol, opioids or illicit drugs also are being used. Additionally, withdrawal symptoms were reported to last several months for some patients. Members in the class include alprazolam (Xanax®, generics), clonazepam (Klonopin®, generics), diazepam (Diastat®/Diastat Acudial, Valium®, Valtoco®, generics), lorazepam (Ativan®, generics), temazepam (Restoril®, generics) and triazolam (Halcion®, generics). A series of FDA Safety Communications, along with other information, can be found here.

MedWatch Update - Diphenhydramine

An FDA safety communication dated Sept. 24, 2020, warns about taking higher than recommended doses of diphenhydramine. Available as the brand, Benadryl®, and multiple generics, diphenhydramine is sold without a prescription primarily to treat allergies. Recently, social media posts, especially among teens and young adults, have promoted the “Benadryl Challenge”, which suggests that taking it in very large amounts can result in euphoric highs or hallucinations. However, large doses can cause serious side effects such as agitation, confusion, vision changes and vomiting. In some cases, seizures and heart rhythm disturbances have occurred. The FDA is investigating reports of emergency room visits and deaths that have been associated with the challenge. Parents and health providers are advised to discuss the risks with children and adolescents who may be tempted to try it. All medications should be kept out of the reach of children – preferably in locked containers. The FDA’s notice has additional information.

Expanded Indication for Kalydeco

On Sept. 25, 2020, the FDA extended the age range for patients eligible for treatment with Kalydeco® (ivacaftor – Vertex) to infants at least four months old. Previously indicated for patients six months of age and older, Kalydeco treats cystic fibrosis (CF) that has mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Additionally, patients must be shown by an FDA-approved diagnostic test to be responsive to treatment with ivacaftor.By potentiating CFTR, Kalydeco helps to keep ion channels functional, which increases the flow of water and salts into and out of cells. Dosing for patients between four months old and six years old begins at 25mg twice a day and increases 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. Here is updated prescribing information.

FDA Approves Nucala to Treat Hypereosinophilic Syndrome

The FDA awarded an additional indication to GlaxoSmithKline’s Nucala® (mepolizumab) on Sept. 25, 2020. Earlier approved to treat eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (EGPA), the monoclonal antibody now can be used for treating patients at least 12 years old who have hypereosinophilic syndrome (HES). A group of rare conditions, HES is estimated to affect only three to four individuals per one million. It produces consistently high levels of eosinophils (a kind of white blood cells) that cannot be associated with a definite primary trigger, such as a parasitic infection. Excessive eosinophils accumulate in body tissues, causing inflammation and organ damage. Nucala is believed to keep an eosinophil growth factor, interleukin 5 (IL-5), from sticking to eosinophils, thereby decreasing eosinophil levels to more normal amounts. To treat HES, the recommended dose is 300mg once a month. Dispensed in 100mg single-use vials and 100mg prefilled syringes, Nucala is given  by SC injection. For its updated prescribing information, look here.

New Indication for Fetroja

Fetroja® (cefiderocol – Shionogi) received an additional approval on Sept. 25, 2020, from the FDA. A cephalosporin antibiotic, it originally was approved in the U.S. on Nov. 15, 2019, to treat complicated urinary tract infections (cUTI). It now also has indications for treating adults who have hospital-acquired pneumonia or ventilator-associated pneumonia that are caused by specific Gram-negative bacteria. In addition to spreading into bacterial cells like other antibiotics, Fetroja uses a unique way to enter and attack bacterial cells by piggybacking onto iron molecules that are needed by bacteria to survive and divide. It is administered as a 2gm IV infusion once every eight hours, typically for seven to 14 days. Here is prescribing information for Fetroja.

Xeljanz Approved for New Indication and Dosage Form

Pfizer was granted FDA approval on Sept. 25, 2020, for Xeljanz® (tofacitinib) to treat children aged two years and older for active polyarticular course juvenile idiopathic arthritis (pcJIA). At the same time, a 1mg/mL oral solution form of Xeljanz also was FDA approved to make dosing easier for small children and those who cannot swallow tablets. It is not interchangeable with Xeljanz® XR extended-release tablets. The oral solution will be introduced in the first quarter of 2021. Arthritis affects at least five joints – including large joints, such as the knees, and small joints in the hands and feet -- for patients who have pcJIA. While not all who are affected have the polyarticular form of the disease, about 300,000 children and teens are thought to have some form of JIA, which begins before age 16 years and lasts for six or more consecutive weeks. A Janus kinase (JAK) inhibitor that blocks inflammation, Xeljanz has prior FDA approvals for the treatment of some adults who have rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ulcerative colitis (UC). Xeljanz is used as monotherapy or along with methotrexate or other non-biologic disease-modifying antirheumatic drugs (DMARDs). However, it should not be taken at the same time as biologic DMARDs or immunosuppressants, such as azathioprine and cyclosporine. For patients who have apJIA and who weigh 40kg (88 pounds) or more, the recommended dose is 5mg twice a day. For patients weighing less than 40kg, doses are determined according to weight. The labeling for Xeljanz contains a boxed warning about the medication’s potential risk of causing serious infections, blood clots and cancer. For its complete prescribing information, look here.

Simponi Aria Also Gets pJIA Indication

Simponi Aria® (golimumab – Janssen) received a new FDA approval on Sept. 29, 2020. Already indicated to treat adults who have ankylosing spondylitis (AS), PsA and RA, it now is approved to treat pJIA for children as young as two years old. The FDA also expanded the PsA indication to pediatric patients in the same age group. A tumor-necrosis factor (TNF) blocker, Simponi Aria is given by 30-minute IV infusions to reduce inflammation. For children, after the first two doses are given four weeks apart, dosing is on an eight-week basis at 80mg/m2. All drugs in the TNF inhibitor class 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 Simponi Aria prescription outlines its potential risks for patients. Check here for revised prescribing information.

Haegarda Approved for Pediatric Use

In a press release dated Sept. 28, 2020, CSL Behring revealed that the indication for its Haegarda® (C1 esterase inhibitor subcutaneous [human]) was extended by the FDA to patients who are as young as six years old. It is indicated for routine prophylaxis to prevent attacks of hereditary angioedema (HAE). A genetic disorder caused by a deficiency of C1 inhibitor, HAE affects between 6,000 and 10,000 patients in the U.S. Patients with the disease experience recurrent, unpredictable, potentially life-threatening inflammatory attacks – generally in the larynx, abdomen, face, extremities and urogenital tract. Intended for SC injection by the patient or caregiver, Haegarda comes in single-dose vials that contain 2,000 International Units (IU) or 3,000 IU of active drug for reconstitution. The recommended dose is 60 IU of Haegarda per kg of body weight once every three or four days. Shire’s C1 esterase inhibitor, Cinryze®, also is FDA approved for the same indication, age range and dosing schedule. However, it has to be administered as IV infusions. Neither Haegarda nor Cinryze is approved to treat acute attacks of HAE. Check herefor Haegarda’s prescribing information.

FDA Approves Alkindi Sprinkle

A new oral formulation of hydrocortisone (also called cortisol), Alkindi® Sprinkle, was approved by the FDA on Sept. 29, 2020. It is indicated to replace cortisol and possibly aldosterone for children and adolescents up to the age of 17 years who have a rare condition, adrenocortical insufficiency, also known as Addison’s disease. The adrenal glands of patients who have the disorder do not produce enough cortisol, which results in low blood pressure, premature puberty, mental status changes, shortness and other symptoms. Potentially life-threatening adrenal crises may happen if cortisol gets too low. Adrenocortical insufficiency can be hereditary, it can be due to an autoimmune disease or it can result from another disorder, such as an infection. Between 5,000 and 10,000 pediatric patients in the U.S. are believed to have it. Supplied in the form of granules that are packed into capsules, Alkindi Sprinkle will be available in 0.5mg. 1mg, 2mg and 5mg strengths, to help make dosing more accurate. Once the capsules are opened, the contents can be emptied directly into the patient’s mouth or mixed with a spoonful of soft food for administration. Recommended initial daily dosing is 8mg to 10mg/m2 rounded to the nearest 0.5mg or 1mg and divided into two or three doses. The manufacturer, Eton pharmaceuticals, plans a launch through its partner, Diurnal Group, in the fourth quarter of 2020. Prescribing information can be found here.

Generic to Tykerb Launched

Lupin Pharmaceuticals has released lapatinib tablets, 250mg in the United States. The generic for Tykerb® – Novartis, lapatinib is used along with other drugs to treat certain types of breast cancer. It is an orally administered small molecule that blocks two proteins, tyrosine kinase EGFR (ErbB1) and HER2 (ErbB2) receptors, that are involved in cancer growth. IQVIA estimated that Tykerb brought in $61 million in U.S sales for the 12-month period that ended on June 30, 2020.

Truvada and Atripla Generics Available

Under a patent lawsuit settlement, Teva Pharmaceuticals USA launched AB-rated generics for two of Gilead’s HIV drugs, Truvada® (emtricitabine/tenofovir disoproxil fumarate, which is abbreviated as TDF) tablets and Atripla®(efavirenz/emtricitabine/TDF) tablets, when the Truvada patent expired on Sept. 30, 2020. Both are used to treat HIV-1 and the two-drug combination also is approved to prevent HIV-1 infections as pre-exposure prophylaxis (PrEP). Either is taken once a day. Both drugs have boxed warnings that discontinuing emtricitabine or TDF may reactivate hepatitis B (HBV) for patients who have both HIV-1 and HBV. Labeling for emtricitabine/TDF also cautions that some patients may experience lactic acidosis while using it and that patients using it for PrEP must be tested for HIV status before beginning treatment and periodically during therapy. Other companies also have FDA approvals for Truvada generics, but a settlement agreement between Gilead and Teva allowed Teva to release its generics about one year ahead of any others. In 2016, Gilead introduced a new combination HIV drug, Descovy® (emtricitabine/tenofovir alafenamide – abbreviated as TAF) tablets. While TAF is similar to TDF, it is effective in smaller doses, so it has less risk of causing kidney damage and bone mineral density problems than TDF. Descovy was FDA approved on Oct. 3, 2019, as PrEP for many individuals who do not have HIV-1, but who are at high risk of acquiring it. Since then, an estimated 43% of patients who were taking Truvada have been switched to Descovy. In 2019, U.S. sales of Truvada were approximately $2.6 billion and Atripla sales were around $500 million.


Stay Informed
Subscribe to our newsletter for regular updates and the latest thinking from our experts.