FDA Update: February 2019

Feb 19, 2019

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

New Pill Bottle

Pediatric Indication for Sprycel

Bristol-Myers Squibb announced that the U.S. Food and Drug Administration (FDA) approved Sprycel® (dasatinib) tablets for children as young as one year old on Dec. 21, 2018. Sprycel is a tyrosine kinase inhibitor (TKI) that is used, along with chemotherapy (chemo), as initial treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). According to the National Institutes of Health (NIH), about one-fifth of U.S. cancer patients under the age of 20 years have ALL and approximately 3,000 children and teens are diagnosed with it, annually. Around 3% of pediatric ALL cases involve the Ph+ subtype, a chromosome abnormality responsible for a specific mutation of the BCR-ABL gene. The recommended dose for patients who weigh at least 45kg (about 100 pounds) is 100mg per day. For patients who weigh less, doses are based on body weight. In clinical trials, tablets were dissolved in fruit juice or other liquids for patients who could not swallow whole tablets. Bone growth should be monitored for pediatric and adolescent patients because Sprycel can cause malformations or pain as bones develop. Sprycel, which has been on the U.S. market since 2006, also  is indicated to treat certain adults and children with Ph+ chronic myeloid leukemia and adults with Ph+ ALL with resistance or intolerance to prior therapy. Its complete revised prescribing information is available here.

FDA Approves Additional Strengths for Apadaz

On Jan. 7, 2019, KemPharm announced that Apadaz® (benzhydrocodone/acetaminophen) tablets has been approved by the FDA for two more strengths. An immediate-release opioid/acetaminophen combination product, Apadaz is a C-II controlled substance indicated for treating intense, acute pain that has not responded to other therapies. Originally approved last year as benzhydrocodone 6.12mg/acetaminophen 325mg, it also now is approved as tablets containing 4.08mg or 8.16mg of benzhydrocodone combined with 325mg of acetaminophen. The recommended dose is one or two tablets every four to six hours as needed. No more than 12 tablets should be taken in any 24-hour period and treatment should last no longer than two weeks. The benzhydrocodone component is a prodrug that is activated by gastrointestinal (GI) enzymes. Crushing it to inhale, inject or smoke will not produce the euphoria associated with misuse of other immediate-release opioids. However, it still can be abused by swallowing. Therefore, the FDA does not consider it to be abuse deterrent and does not allow abuse-deterrent claims on labeling for Apadaz. All opioids have several boxed warnings, including risks for abuse, addiction, misuse, overdose and respiratory depression. They caution about neonatal withdrawal syndrome for babies born to women who used opioids while pregnant, as well. Apadaz will be dispensed with a Medication Guide and under a Risk Evaluation and Mitigation Strategy (REMS). Although KemPharm has not yet announced its launch or pricing plans, it has entered into an agreement with KVK Tech to manufacture, market and distribute all three strengths of Apadaz in the U.S. Full prescribing information can be found here.

Cabometyx Approved for Hepatocellular Carcinoma

Exelixis received approval from the FDA on Jan. 14, 2019, for a new Cabometyx® (cabozantinib) tablets indication. Initially FDA approved in April 2016 to treat advanced renal cell carcinoma (RCC), Cabometyx now also is indicated for treating hepatocellular carcinoma (HCC) after at least one prior therapy with Nexavar® (sorafenib - Bayer). The most common type of liver cancer, HCC is expected to cause about 32,000 deaths this year in the U.S. Affecting approximately twice as many men as women, it is associated with chronic liver diseases such as hepatitis and non-alcoholic steatohepatitis (NASH). The recommended dose of Cabometyx is 60mg once a day at least an hour before or two hours after eating. Full prescribing information is located here.

Generic Sabril Approved

Teva Pharmaceuticals won FDA approval on Jan. 16, 2019, for vigabatrin 500mg tablets, the first generic for Lundbeck’s Sabril® tablets. Vigabatrin is indicated in combination with other drugs to treat complex partial (focal) seizures for patients 10 years and older who have been treated unsuccessfully with multiple other drugs. For patients up to 16 years of age, the recommended dose depends on body weight. Adult dosing begins at 500mg twice a day and increases to a recommended maintenance dose of 1500mg twice a day. Vigabatrin carries a boxed warning that a significant number of patients who use it gradually lose their sight, which does not return. It also has a Risk Evaluation and Mitigation Strategy (REMS). According to IQVIA, U.S. sales of Sabril tablets totaled over $508 million for 2017. Generics for the oral solution dosage form of vigabatrin have been available since May 2018.

Ontruzant Approved to Treat Breast Cancer

Ontruzant® (trastuzumab-dttb – Samsung Bioepsis) for solution for injection received approval from the U.S. Food and Drug Administration (FDA) on Jan. 18, 2019. A biosimilar to Herceptin® (trastuzumab - Genentech), it is indicated in combination with other drugs for treating HER2-overexpressing breast cancer, metastatic breast cancer and metastatic gastric cancer or gastroesophageal junction adenocarcinoma in patients who have not received prior treatment for metastatic disease. Recommended doses vary according to the condition being treated. All trastuzumab products have boxed warnings that they may cause birth defects, heart failure, respiratory collapse or severe allergic reactions. Ontruzant will compete with previously FDA-approved biosimilars for Herceptin – Ogivri® (trastuzumab-dkst – Mylan/Biocon) and Herzuma® (trastuzumab-pkrb – Celltrion/Teva), which have been approved but not yet launched. None of the biosimilars is interchangeable with Herceptin or another biosimilar. Merck will market Ontruzant in the U.S. with a planned launch in the second half of 2019. IQVIA estimates that U.S. sales of Herceptin topped $2.8 billion in 2017. Prescribing information is available here.

Tosymra Approved to Treat Migraines

Tosymra (sumatriptan nasal spray) 10mg was approved by the FDA on Jan. 25, 2019. A new strength of sumatriptan nasal spray that uses a novel formulation, it treats adults who have migraine headaches with or without an aura. The recommended dose is one spray with up to two additional sprays at least one hour apart if pain is not controlled. No more than three doses should be used in any 24-hour period. It should not be used to prevent migraines. Tosymra is packaged in single-dose, disposable spray devices. It is not interchangeable with Imitrex® (sumatriptan nasal spray 5mg and 20mg), generics to Imitrex nasal spray or Onzetra® Xsail® (sumatriptan nasal powder for inhalation). Promius Pharma, the U.S. subsidiary of Dr. Reddy’s Laboratories, has not yet finalized its plans to commercialize Tosymra. Full prescribing information can be found here.

New Indication for Imbruvica

An oral drug, Imbruvica® (ibrutinib – AbbVie/Pharmacyclics), was FDA approved for a new indication on Jan. 25, 2019. In combination with Gazyva® (obinutuzumab – Genentech) injection, it is approved as initial treatment for adults who have chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Imbruvica is a Bruton’s tyrosine kinase (BTK) inhibitor and Gazyva is a CD20-directed monoclonal antibody that targets cancer cells both directly and along with the body’s immune system. Recommended dosing is 420mg of Imbruvica each day. After four loading doses in the first 28-day cycle, 1,000mg of Gazyva is infused intravenously (IV) on only the first days of five successive cycles, after the dose of Imbruvica is taken. Gazyva has boxed warnings that it may cause hepatitis B to recur for patients who have or have had hepatitis B and that it rarely may cause progressive multifocal leukoencephalopathy (PML), a potentially fatal brain infection. Both drugs have indications for other types of cancer. Prescribing information is located here.

FDA Grants Osphena a New Indication

Duchesnay’s Osphena® (ospemifene) was FDA approved to treat moderate to severe vaginal dryness on Jan. 25, 2019. Initially approved in 2013 for treating moderate to severe dyspareunia (painful intercourse), Osphena is not a hormone. It is an oral selective estrogen receptor modulator (SERM) that activates some estrogen receptors and blocks others. Both of its indications result from vulvar and vaginal atrophy (VVA), due to menopause. Recommended dosing is one 60mg tablet daily. Due to its estrogenic effects, Osphena’s labeling has a boxed warning highlighting potential increased risks of uterine cancer, stroke and deep vein thrombosis. Updated full prescribing information is available here.

First Generic to Advair Diskus Approved

On Jan. 30, 2019, the U.S. Food and Drug Administration (FDA) approved Mylan’s Wixela Inhub (fluticasone propionate/salmeterol inhalation powder). It is the first A-rated generic to GlaxoSmithKline’s Advair Diskus® to be approved in the United States. Mylan received approval to market generics for all three currently marketed strengths of Advair Diskus: fluticasone propionate 100mcg/salmeterol 50mcg, 250mcg/50mcg and 500mcg/50mcg. GlaxoSmithKline’s possible plans to launch an authorized generic are still unclear. Mylan is planning to launch Wixela Inhub during the second half of February. Pricing and prescribing information are not yet available. U.S. annual sales for Advair Diskus are approximately $4.19 billion, according to IQVIA. Other companies developing generics to Advair Diskus include Sandoz, Hikma/Vectura and Teva. However, additional generic competition is not expected until 2020.

Alimta Receives Expanded Indication

On Jan. 30, 2019, accelerated approval for Eli Lilly’s Alimta® (pemetrexed) injection was converted to full approval by the FDA, based on results from an additional clinical trial. In combination with Keytruda® (pembrolizumab – Merck) and platinum-based chemo, Alimta now is fully approved as initial treatment for patients who have metastatic nonsquamous non-small cell lung cancer (NSCLC) that does not have epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. Dosing is on three-week cycles with Alimta and Keytruda administered on the first day of each cycle. For the first four cycles, a platinum-based drug is given, as well. Alimta works by blocking enzymes that cancer cells need to grow. Keytruda, a programmed death receptor-1 (PD-1)-blocking antibody, is an immunotherapy drug that helps the body’s immune system attack cancer cells. Cancer drugs that contain platinum destroy cancer cells by altering their DNA. In clinical trials, 47% of patients receiving the three-drug regimen responded at least partially to treatment, as compared to only 18% of those given Alimta, platinum-based chemo and a placebo. Updated prescribing information for Alimta is located here.

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