New Drug Launches
FDA Approves First Drug for Rare Skin Cancer
Last week, the U.S. Food and Drug Administration approved the first treatment, Bavencio® (avelumab), for Merkel cell carcinoma (MCC). Bavencio received accelerated approval for adults and pediatric patients 12 years and older with metastatic MCC, including for patients who have not received prior chemotherapy. As a result of the accelerated approval, continued approval for this indication may require verification of benefit in a confirmatory clinical trial.
Merkel cell carcinoma is an aggressive type of skin cancer usually presenting as a localized tumor which can be removed with surgery. However, half of patients experience recurrence of the cancer and more than 30% develop metastatic cancer. Bavencio is a monoclonal antibody which binds to programmed death ligand-1 (PD-L1), blocking the interaction of PD-L1 with its receptor. This results in restoration of immune responses including anti-tumor responses and subsequently reduces tumor growth.
Bavencio was approved based on data from a single-arm study in 88 patients with metastatic MCC who had received prior treatment with at least one chemotherapy regimen. Thirty-three percent of patients experienced complete or partial shrinkage of their tumors with the duration of response lasting for greater than 6 months in 86% of patients who responded. The most common side effects of Bavencio include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reactions, rash, decreased appetite, and swelling of the extremities. Serious side effects include infusion-related reactions and immune-mediated reactions, such as inflammation of the lungs, liver, colon, and other organs.
Bavencio is administered by intravenous (IV) infusion as a weight-based dose of 10 mg/kg over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. Due to the potential for infusion reactions, patients should receive premedication with an antihistamine and acetaminophen before the first four infusions. Bavencio carries an average wholesale price (AWP) of $180.48 per mL (20 mg/mL). For a 70 kg patient, the AWP for one dose of Bavencio is $6,316.80. NPS will be reviewing Bavencio for placement on the national formularies.
For additional information, please view the FDA’s press release.
FDA Approves New Drug for Breast Cancer
On March 13th, the U.S. Food and Drug Administration (FDA) approved Kisqali® (ribociclib) for the treatment of postmenopausal women with a certain type of breast cancer. Kisqali is indicated for use in combination with an aromatase inhibitor (such as letrozole) for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer. It is specifically for use in the first-line setting for patients requiring endocrine-based therapy. Kisqali received Breakthrough Therapy designation as well as a Priority Review.
Breast cancer is one of the most common cancers in the U.S., and it is estimated more than 250,000 women will be diagnosed with invasive breast cancer this year. Kisqali is a kinase inhibitor that inhibits two proteins known as cyclin-dependent kinase 4 and 6 (CDK 4/6). When these proteins are over-active they can contribute to cancer cell growth. By inhibiting CDK 4/6, Kisqali inhibits tumor growth by decreasing cancer cell proliferation.
The safety and efficacy of Kisqali was demonstrated in a phase 3 study, MONALEESA-2, evaluating 688 patients who had not received any prior systemic therapy for advanced breast cancer. Patients were randomized to receive either ribociclib + letrozole or placebo + letrozole until disease progression or unacceptable toxicity. At the first interim analysis, it was found the addition of ribociclib reduced the risk of disease progression or death by 44%. In addition, the patients in the group which received ribociclib had higher partial or complete tumor response (overall response rates) as compared to patients who only received letrozole (53% vs. 37%). A subsequent analysis demonstrated a median progression-free survival of 25 months for ribociclib + letrozole compared with 16 months for placebo + letrozole.
The most common side effects associated with ribociclib include decreased white blood cell counts, nausea and vomiting, fatigue, diarrhea, constipation, hair loss, headache, and back pain. Due to the potential for QT interval prolongation, electrocardiograms (ECGs) and electrolytes should be monitored prior to initiation of therapy. An ECG should be repeated at day 14 of the first cycle, at the beginning of the second cycle, and as clinically indicated. Electrolytes should be monitored at the beginning of each cycle for 6 cycles and as clinically indicated.
Kisqali is commercially available and is supplied as a 200 mg oral tablet. The recommended starting dose is 600 mg once daily for 21 days followed by 7 days without treatment. Dose reductions may be required for patients who experience adverse effects. The average wholesale price (AWP) for a 200 mg tablet is $208.57 to $250.29 with the lower cost per tablet being associated with the recommended dosing of three tablets per day. Kisqali is expected to compete directly with Ibrance® (palbociclib), another oral CDK 4/6 inhibitor also indicated for HR+/HER2- advanced or metastatic breast cancer. NPS is planning to review Kisqali for placement on the national formularies.
For additional information, please view the manufacturer’s press release.
New Drug Approvals
FDA Approves First Biologic for Atopic Dermatitis
Earlier this week, the U.S. FDA approved Dupixent® (dupilumab) for the treatment of patients with moderate-to-severe atopic dermatitis. Dupixent is indicated specifically for adults with atopic dermatitis whose disease is not adequately controlled with topical therapies or for whom topical therapies are not appropriate. It can be used with or without topical corticosteroids.
Eczema is a term used to describe multiple types of skin inflammation, and atopic dermatitis is the most common type of eczema. Patients with atopic dermatitis generally experience a rough, red itchy rash on the face, arms or legs, primarily beginning in childhood and in some patients lasting through adulthood. Scratching of the area affected may lead to swelling, cracking, and thickening of the skin. Atopic dermatitis may be caused by a number of factors including genetic predisposition as well as environmental triggers. Dupixent is a monoclonal antibody that binds to the interleukin-4 (IL-4) receptor. By binding to the IL-4 receptor, Dupixent prevents inflammatory signaling by IL-4 which reduces the inflammatory response contributing to atopic dermatitis.
The efficacy and safety of Dupixent were evaluated in three placebo-controlled clinical studies evaluating over 2,000 adults with moderate-to-severe atopic dermatitis. Patients had disease not adequately controlled by topical medications. At 16 weeks of therapy, a greater proportion of patients who received Dupixent achieved clear or almost clear skin compared to patients who received placebo. The most common side effects of Dupixent, occurring in 1% or more of patients treated, include: injection site reactions, eye problems such as pink eye, dry eye, inflammation of the cornea or eyelid, oral cold sores, and other herpes simplex virus infections. Dupixent also has the potential to cause serious allergic hypersensitivity reactions.
Dupixent is administered by subcutaneous injection with a recommended initial dose of 600 mg (two 300 mg injections), followed by 300 mg every other week. It is expected to be commercially available by the end of the week and will be supplied in a prefilled syringe for self-administration. NPS is planning to review Dupixent for placement on the national formularies. For additional information, please view the FDA’s press release.
FDA Safety Update
Avoid Viberzi® in Patients Without a Gallbladder
Earlier this month, the U.S. FDA issued a warning regarding use of the irritable bowel syndrome medication Viberzi® (eluxadoline) in patients without a gallbladder. The FDA found patients who do not have a gallbladder and take Viberzi have an increased risk of serious pancreatitis which could result in hospitalization or death. Since approval of Viberzi in May 2015 through February 2017, the FDA has received 120 reports of serious pancreatitis or death. Over half of these patients reported their gallbladder status, and the majority of them did not have a gallbladder.
Viberzi is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults. It acts to decrease bowel contractions resulting in less diarrhea, and can decrease the accompanying abdominal pain. Pancreatitis has occurred with only one or two doses of Viberzi at the recommended dosage of 75 mg in patients who do not have a gallbladder and do not consume alcohol. As a result, health care providers should not prescribe Viberzi to individuals without a gallbladder and alternative therapies should be considered. Potential alternative therapies include over-the-counter (OTC) bismuth subsalicylate (Pepto-Bismol®, Kaopectate®), OTC loperamide (Imodium®), or the prescription product diphenoxylate/atropine (Lomotil®). FDA-approved prescription drugs for IBS-D include alosetron (Lotronex®) and rifaximin (Xifaxan®).
Pancreatitis can be caused by a spasm of digestive system muscles in the small intestine. Symptoms can include new or worsening stomach pain or pain in the upper right side of the stomach area that radiates to the back or shoulder with or without nausea and vomiting. If patients taking Viberzi experience these symptoms, they should stop taking Viberzi immediately and seek medical attention. In addition, patients are instructed to speak with their health care provider, if they have IBS-D and do not have a gallbladder, in order to discuss appropriate options for managing their IBS-D symptoms.
For additional information, please view the FDA’s Drug Safety Communication.
Generic Pristiq® Now Available
A generic of the antidepressant Pristiq® (desvenlafaxine succinate extended-release) has been approved by the FDA and is commercially available. Pristiq and its generic, desvenlafaxine, are indicated for the treatment of major depressive disorder. The brand and generic products are available as an oral extended release tablet in the strengths of 25 mg, 50 mg, and 100 mg.
The recommended starting dose of desvenlafaxine is 50 mg once daily taken at the same time each day, with or without food. Tablets should be swallowed whole and should not be divided, crushed, chewed, or dissolved. Doses of 50 mg to 400 mg per day have been demonstrated to be effective, however no additional benefit was observed at doses greater than 50 mg per day. Side effects and therapy discontinuation were also more common at higher doses. The 25 mg tablet is used for tapering of doses when therapy is being discontinued.
Pristiq carries an average wholesale price (AWP) of $12.75 per each oral tablet, and the generic carries an AWP of between $11.46 and $11.95 per tablet. NPS is planning to review the generic desvenlafaxine tablets for placement on the national formularies.
Nitro-Dur® Patch Discontinued
Earlier this month, Merck announced discontinuation of their nitroglycerin transdermal infusion system Nitro-Dur®. The product is being discontinued due to a business decision and is not due to any safety concerns. Nitro-Dur is a transdermal infusion system that provides continuous controlled release of nitroglycerin through the skin. It is indicated for prevention of chest pain due to coronary artery disease.
Final sale dates for each of the presentations have been released by the manufacturer. Some presentations will be discontinued immediately (0.1 mg/hour, 30 unit doses) while others will be phased out between now and November 2018. Nitroglycerin will continue to be available as a generic transdermal patch and as the brand-name product Minitran®. These products are available in the strengths of 0.1 mg/hour, 0.2 mg/hour, 0.4 mg/hour, and 0.6 mg/hour. However, Nitro-Dur is the only transdermal patch preparation available in the strengths of 0.3 mg/hour and 0.8 mg/hour.
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- Novartis Kisqali (ribociclib, LEE011) receives FDA approval as first-line treatment for HR+/HER2- metastatic breast cancer in combination with any aromatase inhibitor. Novartis News Release. https://www.novartis.com/news/media-releases/novartis-kisqalir-ribociclib-lee011-receives-fda-approval-first-line-treatment. Updated March 13, 2017. Accessed March 23, 2017.
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- FDA approves new eczema drug Dupixent. FDA News Release. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm549078.htm. Updated March 28, 2017. Accessed March 28, 2017.
- Dupixent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; March 2017. https://www.regeneron.com/sites/default/files/Dupixent_FPI.pdf. Accessed March 28, 2017.
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- Dupixent wins FDA approval to treat moderate-to-severe atopic dermatitis. P&T Community. https://www.ptcommunity.com/news/20170328/dupixent-wins-fda-approval-treat-moderate-severe-atopic-dermatitis. Updated March 28, 2017. Accessed March 29, 2017.
- FDA Drug Safety Communication: FDA warns about increased risk of serious pancreatitis with irritable bowel drug Viberzi (eluxadoline) in patients without a gallbladder. U.S. Food & Drug Administration. https://www.fda.gov/Drugs/DrugSafety/ucm546154.htm. Updated March 15, 2017. Accessed March 29, 2017.
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