FDA Approves Repatha

• FDA approved: Yes (First approved August 27th, 2015)
• Brand name: Repatha
• Generic name: evolocumab
• Company: Amgen Inc.
• Treatment for: High Cholesterol, Familial Heterozygous, High Cholesterol, Familial Homozygous,High Cholesterol

Repatha (evolocumab) is a monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) for the treatment of patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, or patients with atherosclerotic heart disease who require additional lowering of LDL-cholesterol.The FDA approved Amgen’s Repatha (evolocumab) for U.S. marketing on August 27, 2015. Repatha injection is indicated for use in addition to diet and maximally-tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH), homozygous familial hypercholesterolemia (HoFH), or clinical atherosclerotic cardiovascular disease (ASCVD), such as heart attacks or strokes, who require additional lowering of LDL cholesterol.

Prior to full approval, Repatha underwent FDA advisory committee review on Wednesday, June 10th, 2015. The FDA committee voted 11-4 in favor of FDA approval, including a 15-0 approval for homozygous familial hypercholesterolemia (HoFH).In Phase 3 trials evolocumab lowered LDL-C by roughly 60% across all study groups in 12- and 52-week studies; in HoFH, evolocumab reduced LDL-C by 31%. FDA briefing documents lists further clinical study details.

Common side effects with Repatha use include nasopharyngitis (common old), upper respiratory tract infections, influenza, back pain, and injection site reactions like redness, pain or bruising. Allergic reactions, such as rash and hives, have been reported. Patients should stop using Repatha and seek emergency medical care if they experience symptoms of a serious allergic reaction, such as swelling of the lips, tongue or throat.Repatha is the second PCSK9 inhibitor drug to be approved this summer. Sanofi-Aventis and Regeneron’s Praluent (alirocumab) was given the agency go-ahead on July 24, 2015 for treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of low-density lipoprotein (LDL) cholesterol.

The recommended dose of Repatha for adults is 140 mg every two weeks or 420 mg once a month. Repatha is available as a single-use 140 mg prefilled autoinjector or prefilled syringe that patients can self-administer. For adults with HoFH, the recommended dose is 420 mg once a month.Repatha is expected to be available in the U.S. next week. According to Amgen, the Wholesale Acquisition Cost (WAC) of Repatha is $14,100 annually for the every two weeks administration. Actual costs to patients, payers and health systems are anticipated to be different, based on pricing negotiations, insurance coverage or patient assistance programs.Repatha, the second drug approved in a new class of drugs known as PCSK9 inhibitors, is approved for use in addition to diet and maximally-tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH), homozygous familial hypercholesterolemia (HoFH), or clinical atherosclerotic cardiovascular disease, such as heart attacks or strokes, who require additional lowering of LDL cholesterol.

Familial hypercholesterolemia (encompassing both HeFH and HoFH) is an inherited condition that causes high levels of LDL cholesterol. A high level of LDL cholesterol in the blood is linked to cardiovascular or heart disease. Heart disease is the number one cause of death for Americans, both men and women. According to the Centers for Disease Control and Prevention, about 610,000 people die of heart disease in the United States every year– that equals one in every four deaths.

“Repatha provides another treatment option in this new class of drugs for patients with familial hypercholesterolemia or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough with statins,” said John Jenkins, M.D., director of the Office of New Drugs, Center for Drug Evaluation and Research. “Cardiovascular disease is a serious threat to the health of Americans, and the FDA is committed to facilitating the development and approval of effective and safe drugs to address this important public health problem.”Repatha is an antibody that targets a specific protein, called PCSK9. PCSK9 reduces the number of receptors on the liver that remove LDL cholesterol from the blood. By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels.

The efficacy and safety of Repatha were evaluated in one 52-week placebo-controlled trial and eight 12-week placebo-controlled trials in participants with primary hyperlipidemia, including two that specifically enrolled participants with HeFH and one that enrolled participants with HoFH. In one of the 12-week studies, 329 participants with HeFH, who required additional lowering of LDL cholesterol despite statins with or without other lipid-lowering therapies, were randomized to receive Repatha or placebo for 12 weeks. Participants taking Repatha had an average reduction in LDL cholesterol of approximately 60 percent, compared to placebo.

The most common side effects of Repatha include nasopharyngitis, upper respiratory tract infection, flu, back pain, and reactions such as redness, pain, or bruising where the injection is given. Allergic reactions, such as rash and hives, have been reported with the use of Repatha. Patients should stop using Repatha and get medical help if they experience symptoms of a serious allergic reaction.Multiple clinical trials have demonstrated that statins lower the risk of having a heart attack or stroke. A trial evaluating the effect of adding Repatha to statins for reducing cardiovascular risk is ongoing. Repatha is marketed by Amgen Inc., of Thousand Oaks, Calif.

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FDA Approves Aristada

Aristada

Generic Name: aripiprazole lauroxil
Date of Approval: October 5, 2015
Company: Alkermes, Inc.

Aristada is the first atypical antipsychotic with once-monthly and six-weekly dosing options.

The U.S. Food and Drug Administration (FDA) has approved Aristada (aripiprazole lauroxil), an extended-release injectable atypical antipsychotic for the treatment of patients with schizophrenia.

MEDICATION GUIDE

Read this Medication Guide before you start treatment and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor.

IMPORTANT INFORMATION ABOUT ARISTADA

Each injection of Aristada must be administered by a healthcare professional only.

Aristada may cause serious side effects, including:

• Increased risk of death in elderly people with dementia-related psychosis. Aristada is not for the treatment of people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia).
• Neuroleptic malignant syndrome (NMS) a serious condition that can lead to death.Tell your healthcare provider right away if you have some or all of the following symptoms of NMS:
  • High fever
  • Stiff muscles
  • Confusion
  • Sweating
  • Changes in pulse, heart rate, and blood pressure

Call your healthcare provider right away if you have any of these symptoms.

WHAT IS ARISTADA?

Aristada is a prescription medicine given by injection by a healthcare professional and used to treat schizophrenia. It is not known if it is safe and effective in children under 18 years of age.

WHO SHOULD NOT RECEIVE ARISTADA?

Do not receive Aristada if you are allergic to aripiprazole or any of the other ingredients. See the end of this page for a complete list of active and inactive ingredients.

BEFORE RECEIVING ARISTADA

Before you receive Aristada, tell your healthcare provider if you:

• have never taken Abilify, Abilify Maintena or any aripiprazole product previously
• have diabetes or high blood sugar or a family history of diabetes or high blood sugar. Your healthcare provider should check your blood sugar before and during your treatment.
• have or had seizures (convulsions)
• have or had low or high blood pressure
• have or had heart problems or a stroke
• have or had a low white blood cell count
• have any other medical problems including problems that may affect you receiving an injection in your buttocks or your arm
• are pregnant or plan to become pregnant. It is not known if Aristada will harm your unborn baby.
  • If you become pregnant while taking Aristada, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/
• are breastfeeding or plan to breastfeed. Aristada can pass into your milk and it is not known if it may harm your baby. Talk to your healthcare provider about the best way to feed your baby during treatment.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Aristada and other medicines may affect each other causing possible serious side effects. Aristada may affect the way other medicines work, and vice versa. Your healthcare provider can tell you if it is safe to take Aristada with your other medicines. Do not start or stop any medicines during treatment without talk ing to your healthcare provider first.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

HOW SHOULD I RECEIVE ARISTADA?

• Follow your treatment schedule exactly as your healthcare provider tells you to.
• Each dose is given as an injection in your arm or buttock by your healthcare provider once a month or once every six weeks. You may feel a little pain inyour arm or buttock during the injection.
• After your first injection, you should continue your current antipsychotic medicine for 21 days.
• Do not miss a dose. If you do miss a dose for some reason, call your healthcare provider right away to discuss what you should do next.

What should I avoid while receiving Aristada?

• Do not drive a car, operate machinery, or do other dangerous activities until you know how the treatment affects you. It may make you feel drowsy.
• Do not drink alcohol during treatment.
• Do not become too hot or dehydrated during treatment.
  • Do not exercise too much.
  • In hot weather, stay inside in a cool place if possible.
  • Stay out of the sun.
  • Do not wear too much clothing or heavy clothing.
  • Drink plenty of water.

ARISTADA SIDE EFFECTS

Aristada may cause serious side effects, including:

• See Important information about Aristada
• Stroke in elderly people (cardiovascular problems) that can lead to death
• Neuroleptic malignant syndrome (NMS): Tell your healthcare provider right away if you have some or all of the following symptoms: high fever, stiff muscles, confusion, sweating, changes in pulse, heart rate, and blood pressure. These may be symptoms of a rare and serious condition that can lead to death. Call your healthcare provider right away if you have any of these symptoms.
• Uncontrolled body movements (tardive dyskinesia): movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop treatment. Tardive dyskinesia may also start after you stop treatment.
• Problems with your metabolism such as:
  • High blood sugar (hyperglycemia): Increases in blood sugar can happen in some people who take Aristada. Extremely high blood sugar can lead to coma or death. If you have diabetes or risk factors for diabetes (such as being overweight or a family history of diabetes), your healthcare provider should check your blood sugar before you start, and during your treatment.Call your healthcare provider if you have any of these symptoms of high blood sugar while receiving Aristada:
    • Feel very thirsty
    • Feel very hungry
    • Feel sick to your stomach
    • Need to urinate more than usual
    • Feel weak or tired
    • Feel confused, or your breath smells fruity
  • Increased fat levels (cholesterol and triglycerides) in your blood.
  • Weight gain. You and your healthcare provider should check your weight regularly.
• Decreased blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.
• Low white blood cell count
• Seizures (convulsions)
• Problems controlling your body temperature so that you feel too warm. See What should I avoid while receiving Aristada?
• Difficulty swallowing

The most common side effects include feeling like you need to move to stop unpleasant feelings in your legs (restless leg syndrome or akathisia).

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088.

GENERAL INFORMATION ABOUT THE SAFE AND EFFECTIVE USE OF ARISTADA

This Medication Guide summarizes the most important information. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information that is written for health professionals.

WHAT ARE THE INGREDIENTS IN ARISTADA?

Active ingredient: aripiprazole lauroxil

Inactive ingredients: sorbitan monolaurate, polysorbate 20, sodium chloride, sodium phosphate dibasic anhydrous, sodium phosphate monobasic and water for injection

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Cost to Develop and Win Marketing Approval for a New Drug Is $2.6 Billion

Developing a new prescription medicine that gains marketing approval, a process often lasting longer than a decade, is estimated to cost $2,558 million, according to a new study by the Tufts Center for the Study of Drug Development.

The $2,558 million figure per approved compound is based on estimated:

• Average out-of-pocket cost of $1,395 million
• Time costs (expected returns that investors forego while a drug is in development) of $1,163 million

Estimated average cost of post-approval R&D—studies to test new indications, new formulations, new dosage strengths and regimens, and to monitor safety and long-term side effects in patients required by the U.S. Food and Drug Administration as a condition of approval—of $312 million boosts the full product lifecycle cost per approved drug to $2,870 million. All figures are expressed in 2013 dollars.

The new analysis, which updates similar Tufts CSDD analyses, was developed from information provided by 10 pharmaceutical companies on 106 randomly selected drugs that were first tested in human subjects anywhere in the world from 1995 to 2007.“Drug development remains a costly undertaking despite ongoing efforts across the full spectrum of pharmaceutical and biotech companies to rein in growing R&D costs,” said Joseph A. DiMasi, director of economic analysis at Tufts CSDD and principal investigator for the study.

He added, “Because the R&D process is marked by substantial technical risks, with expenditures incurred for many development projects that fail to result in a marketed product, our estimate links the costs of unsuccessful projects to those that are successful in obtaining marketing approval from regulatory authorities.”In a study published in 2003, Tufts CSDD estimated the cost per approved new drug to be $802 million (in 2000 dollars) for drugs first tested in human subjects from 1983 to 1994, based on average out-of-pocket costs of $403 million and capital costs of $401 million.

The $802 million, equal to $1,044 million in 2013 dollars, indicates that the cost to develop and win marketing approval for a new drug has increased by 145% between the two study periods, or at a compound annual growth rate of 8.5%.According to DiMasi, rising drug development costs have been driven mainly by increases in out-of-pocket costs for individual drugs and higher failure rates for drugs tested in human subjects.Factors that likely have boosted out-of-pocket clinical costs include increased clinical trial complexity, larger clinical trial sizes, higher cost of inputs from the medical sector used for development, greater focus on targeting chronic and degenerative diseases, changes in protocol design to include efforts to gather health technology assessment information, and testing on comparator drugs to accommodate payer demands for comparative effectiveness data.

Lengthening development and approval times were not responsible for driving up development costs, according to DiMasi.“In fact,” DiMasi said, “changes in the overall time profile for development and regulatory approval phases had a modest moderating effect on the increase in R&D costs. As a result, the time cost share of total cost declined from approximately 50% in previous studies to 45% for this study.”The study was authored by DiMasi, Henry G. Grabowski of the Duke University Department of Economics, and Ronald W. Hansen at the Simon Business School at the University of Rochester.

ABOUT THE TUFTS CENTER FOR THE STUDY OF DRUG DEVELOPMENT

The Tufts Center for the Study of Drug Development (http://csdd.tufts.edu) at Tufts University provides strategic information to help drug developers, regulators, and policy makers improve the quality and efficiency of pharmaceutical development, review, and utilization. Tufts CSDD, based in Boston, conducts a wide range of in-depth analyses on pharmaceutical issues and hosts symposia, workshops, and public forums, and publishes Tufts CSDD Impact Reports, a bi-monthly newsletter providing analysis and insight into critical drug development issues.

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FDA Approves Onivyde

October 22, 2015 — The U.S. Food and Drug Administration today approved Onivyde (irinotecan liposome injection), in combination with fluorouracil and leucovorin, to treat patients with advanced (metastatic) pancreatic cancer who have been previously treated with gemcitabine-based chemotherapy.

According to the National Cancer Institute, there will be 48,960 new cases of pancreatic cancer diagnosed in the U.S. in 2015, and nearly the same number of deaths caused by the disease (40,560). Pancreatic cancer can be difficult to diagnose early and treatment options are limited, especially when the disease has spread to other parts of the body (metastatic disease) and surgery to remove the tumor is not possible.

“Many FDA staff who review drug applications are clinicians as well, so it’s especially rewarding when we are able to expedite access to new treatments for patients with unmet needs,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “By using the Priority Review designation for the application for Onivyde, patients will have earlier access to a drug that helps extend survival.”

The FDA granted Priority Review and orphan drug designations for Onivyde. Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as tax credits, user fee waivers, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.The effectiveness of Onivyde was demonstrated in a three-arm, randomized, open label study of 417 patients with metastatic pancreatic adenocarcinoma whose cancer had grown after receiving the chemotherapeutic drug gemcitabine or a gemcitabine-based therapy. The study was designed to determine whether patients receiving Onivyde plus fluorouracil/leucovorin or Onivyde alone lived longer than those receiving fluorouracil/leucovorin. Patients treated with Onivyde plus fluorouracil/leucovorin lived an average of 6.1 months, compared to 4.2 months for those treated with only fluorouracil/leucovorin. There was no survival improvement for those who received only Onivyde compared to those who received fluorouracil/leucovorin.

In addition, patients receiving Onivyde plus fluorouracil/leucovorin had a delay in the amount of time to tumor growth compared to those who received fluorouracil/leucovorin. The average time for those receiving Onivyde plus fluorouracil/leucovorin was 3.1 months compared to 1.5 months for those receiving fluorouracil/leucovorin.The safety of Onivyde was evaluated in 398 patients who received either Onivyde with fluorouracil/leucovorin, Onivyde alone or fluorouracil/leucovorin. The most common side effects of treatment with Onivyde included diarrhea, fatigue, vomiting, nausea, decreased appetite, inflammation in the mouth (stomatitis) and fever (pyrexia). Onivyde was also found to result in low counts of infection-fighting cells (lymphopenia and neutropenia). Death due to sepsis following neutropenia has been reported in patients treated with Onivyde.

The labeling for Onivyde includes a boxed warning to alert health care professionals about the risks of severe neutropenia and diarrhea. Onivyde is not approved for use as a single agent for the treatment of patients with metastatic pancreatic cancer. Onivyde is marketed by Merrimack Pharmaceuticals Inc. of Cambridge, Massachusetts.

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Source: FDA

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