FDA Drug Approvals

Relief could be on the way for as many as 63 million people that the National Institutes of Health estimates are affected by chronic constipation. 

The U.S. Food and Drug Administration has approved Linzess (linaclotide) to treat chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C) in adults. 

Chronic idiopathic constipation is a diagnosis given to those who experience persistent constipation and do not respond to standard treatment. An estimated 15.3 million people are affected by IBS. IBS-C is a subtype characterized mainly by abdominal pain and by hard or lumpy stools at least 25 percent of the time and loose or watery stools less than 25 percent of the time. 

The treatment 

Linzess is a capsule taken once daily on an empty stomach, at least 30 minutes before the first meal of the day. The medication helps relieve constipation by helping bowel movements occur more often. In IBS-C, it may also help ease abdominal pain. 

“No one medication works for all patients suffering from these gastrointestinal disorders,” said Victoria Kusiak, M.D., deputy director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research. “With the availability of new therapies, patients and their doctors can select the most appropriate treatment for their condition.” 

Safety and effectiveness 

The safety and effectiveness of Linzess for the management of IBS-C were established in two, double-blind studies. A total of 1,604 patients were randomly assigned to take 290 micrograms of Linzess or a placebo for at least 12 weeks. 

Results showed Linzess was more effective in reducing the amount of abdominal pain and increasing the number of complete spontaneous bowel movements compared with placebo. 

The safety and effectiveness of Linzess for the management of chronic idiopathic constipation also were established in two, double-blind studies. A total of 1,272 patients were randomly assigned to take Linzess at doses of 145 mcg or 290 mcg or a placebo for 12 weeks. 

Results from these studies showed patients taking Linzess experienced more complete spontaneous bowel movements than those taking the placebo. The 290 mcg dose is not approved for chronic constipation because studies indicated it was no more effective than the 145 mcg dose.

Linzess is approved with a Boxed Warning to alert patients and health care professionals that the drug should not be used in patients 16 years of age and younger. The most common side effect reported in during the clinical studies was diarrhea.

The current medication you're using to treat rheumatoid arthritis (RA) not working? You may have an alternative.

The U.S. Food and Drug Administration (FDA) has approved Xeljanz (tofacitinib) to treat adults with moderately to severely active RA who have had an inadequate response to, or who are intolerant of, methotrexate.

RA is an autoimmune disease, in which the body's immune system mistakenly attacks healthy tissue leading to inflammation of the joints and surrounding tissues. According to the Centers for Disease Control and Prevention, RA affects an estimated 1.5 million Americans. Xeljanz, a pill taken twice daily, works by blocking molecules called “Janus kinases,” which are important in the joint inflammation of RA.

A new treatment option

“Xeljanz provides a new treatment option for adults suffering from the debilitating disease of RA who have had a poor response to methotrexate,” said Badrul Chowdhury, M.D., Ph.D., director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

Xeljanz is being approved ahead of the product’s prescription drug user fee goal date of Nov. 21, 2012, the date the agency was scheduled to complete review of the drug application.

The safety and effectiveness of Xeljanz were evaluated in seven clinical trials in adult patients with moderately to severely active RA. In all of the trials, patients treated with Xeljanz experienced improvement in clinical response and physical functioning compared to patients treated with placebo.

Risk of infection

The use of Xeljanz was associated with an increased risk of serious infections, including opportunistic infections (infections that occur primarily when the immune system is suppressed), tuberculosis, cancers and lymphoma. Xeljanz carries a Boxed Warning regarding these safety risks. Xeljanz treatment is also associated with increases in cholesterol and liver enzyme tests and decreases in blood counts.

The FDA approved Xeljanz with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a Medication Guide advising patients about important safety information and a communication plan to inform health care providers about the serious risks associated with Xeljanz.

Post-marketing study required

To study the long-term effects of Xeljanz on heart disease, cancer, and serious infections, the FDA is requiring a post-marketing study that will evaluate two doses of Xeljanz and include a group of patients on another approved treatment to serve as a comparison.

The most common adverse reactions in clinical trials were upper respiratory tract infections, headache, diarrhea, and inflammation of the nasal passage and the upper part of the pharynx.

Xeljanz is marketed by New York-based Pfizer Inc.

Tecfidera (dimethyl fumarate) capsules has won approval from the U.S. Food and Drug Administration (FDA) to treat adults with relapsing forms of multiple sclerosis (MS).

“No drug provides a cure for multiple sclerosis so it is important to have a variety of treatment options available for patients,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Multiple sclerosis can impair movement, sensation, and thinking and have a profound impact on a person’s quality of life.”

Positive results

Results from two clinical trials showed that those taking Tecfidera had fewer MS relapses compared with people taking an inactive pill (placebo). One of the trials showed that those taking Tecfidera experienced a worsening of disability less often than patients taking a placebo.

Tecfidera may decrease a person’s white blood cell count (lymphocytes). Lymphocytes help protect the body from infection and low counts can raise the risk of infection, although no significant increase in infections was seen in patients taking Tecfidera in clinical trials. Before starting treatment, and annually thereafter, the FDA recommends that the patient’s white blood cell count be assessed by their health care provider.

Flushing (warmth and redness) and stomach problems (nausea, vomiting, and diarrhea) were the most common adverse reactions reported by patients receiving Tecfidera in clinical trials, especially at the start of therapy. These side effects may decrease over time.

Young adults at risk

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function (relapses) are initially followed by recovery periods (remissions).

Over time, recovery periods may be incomplete, leading to progressive decline in function and increased disability. MS patients often experience muscle weakness and difficulty with coordination and balance. Most people experience their first symptoms of MS between the ages of 20 and 40.

Tecfidera is made by Biogen Idec, Weston, Mass.

There's a new product on the market for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and or emphysema.

Breo Ellipta (fluticasone furoate and vilanterol inhalation powder), which has been okayed by the U.S. Food and Drug Administration (FDA), is also approved to reduce exacerbations of COPD in patients with a history of exacerbations.

Symptoms of COPD, a serious lung disease that worsens over time, can include chest tightness, chronic cough and excessive phlegm. Cigarette smoking is the leading cause of COPD which, according to the National Heart, Lung, and Blood Institute, is the third leading cause of death in the United States.

Breo Ellipta, a combination of fluticasone furoate, an inhaled corticosteroid, and vilanterol, a long-acting beta2-adrenergic agonist (LABA), works by decreasing inflammation in the lungs and helping the muscles around the airways of the lungs stay relaxed to increase airflow and reduce exacerbations in patients with COPD.

A serious problem

“COPD is a serious disease that makes breathing difficult,” said Curtis Rosebraugh, M.D., M.P.H., director, Office of Drug Evaluation II, Center for Drug Evaluation and Research, FDA. “The availability of new long-term maintenance medications provides additional treatment options for the millions of Americans who suffer with COPD.”

The safety and efficacy of Breo Ellipta were evaluated in 7,700 patients with a clinical diagnosis of COPD. Those treated showed improved lung function and reduced exacerbations compared with those who used a placebo.

Asthma warning

The drug carries a boxed warning that LABAs increase the risk of asthma-related death. The safety and efficacy of Breo Ellipta in patients with asthma have not been established, and it is not approved for the treatment of asthma.

Breo Ellipta carries a patient medication guide that includes instructions for use and information about the potential risks of taking the drug. It should not be used as a rescue therapy to treat sudden breathing problems (acute bronchospasm) and is not recommended for people younger than 18 years.

Serious side effects include increased risks of pneumonia and bone fractures. Among the most common side effects are inflammation of the nasal passage (nasopharyngitis), upper respiratory tract infection, headache and oral candidiasis (thrush).

Breo Ellipta was developed by GlaxoSmithKline in collaboration with Theravance.

Patients with previously untreated chronic lymphocytic leukemia (CLL) have a new treatment option.

The U.S. Food and Drug Administration (FDA) has approved Gazyva (obinutuzumab) for use in combination with chlorambucil.

CLL is a blood and bone marrow disease that usually gets worse slowly. According to the National Cancer Institute, 15,680 people in the U.S. will be diagnosed and 4,580 will die from the disease this year.

The approval “represents an important new addition to the treatments for patients with CLL,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval reflects the promise of the Breakthrough Therapy Designation program, allowing us to work collaboratively with companies to expedite the development, review and availability of important new drugs.”

How it works

Gazyva works by helping certain cells in the immune system attack cancer cells. Gazyva is intended to be used with chlorambucil, another drug used to treat patients with CLL.

It's the first drug with breakthrough therapy designation to receive FDA approval. This designation was requested by the sponsor and granted soon after the biologic license application to support marketing approval was submitted to the FDA.

The FDA can designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

Gazyva was granted priority review because it demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. And the FDA granted Gazyva orphan product designation because it is intended to treat a rare disease.

Side effects

The most common side effects observed in participants receiving Gazyva in combination with chlorambucil were infusion-related reactions, a decrease in infection-fighting white blood cells (neutropenia), a low level of platelets in the blood (thrombocytopenia), low red blood cells (anemia), pain in the muscles and bones (musculoskeletal pain), and fever (pyrexia).

Gazyva is being approved with a boxed warning regarding Hepatitis B virus reactivation and a rare disorder that damages the material that covers and protects nerves in the white matter of the brain (progressive multifocal leukoencephalopathy).

These are known risks with other monoclonal antibodies in this class and rare cases were identified in participants on other trials of Gazyva.

Gazyva is marketed by South San Francisco-based Genentech.

TheU.S. Food and Drug Administrationhas approved Rituxan (rituximab) to treat patients with Wegenergranulomatosis (WG) and microscopic polyangiitis (MPA), two rare disorders that cause blood vessel inflammation (vasculitis).

Rituxan will be usedin combination with steroids.

Vasculitis in patients with WG and MPA can lead to tissue damage. WG mostly affects the respiratory tract (sinuses, nose, trachea, and lungs) and kidneys, while MPA commonly affects the kidneys, lungs, nerves, skin, and joints.

Both of these diseases affect people of all ages and ethnicities, and both genders. The causes of these disorders are unknown, and both are considered orphan diseases because they each affect less than 200,000 people in the United States.

“This new indication for Rituxan provides the first approved therapy for these two orphan diseases,said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA?Center for Drug Evaluation and Research.

Rituxan is an antibody that is manufactured through biotechnology methods. The drug works by greatly reducing the number of specific immune cells in the blood, known as B cells. 

The safety and effectiveness of Rituxan was demonstrated in a single controlled trial, in which 197 patients with WG or MPA were assigned at random to receive either Rituxan plussteroids once a week for four weeks or oral cyclophosphamide plus steroids daily to induce remission. After six months, 64 percent of patients treated with Rituxan had complete remission compared to 53 percent of patients treated with cyclosphosphamide. 

Retreatment with Rituxan was not formally evaluated; therefore, the safety and efficacy of retreatment with subsequent courses of Rituxan has not been established. More data are needed to determine the safety of more than one course of Rituxan and long term safety of use of Rituxan in patients with WG and MPA. These questions will be further evaluated in a required post-marketing study.

Rituxan carries a Boxed Warning for infusion reactions, which can occur during infusion or within 24 hours afterwards. Other Boxed Warnings for Rituxan include rashes and sores in the skin and mouth (severe mucocutaneous reactions); and progressive multifocal leukoencephalopathy, a brain infection that generally is fatal. Rituxan is not recommended for use in patients with severe, active infections.

The most common side effects in study participants with WG and MPA included infection, nausea, diarrhea, headache, muscle spasms, and anemia.

Rituxan, which has been marketed since 1997, is also indicated for the treatment of patients with non-Hodgkin'slymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.

Rituxan is manufactured by San Francisco-based Genentech, a member of the Roche Group.

Gilenya is the first oral drug that can slow the progression of disability and reduce the frequency and severity of symptoms in MS, offering patients an alternative to currently available injectable therapies, said Russell Katz, M.D., director of the Division of Neurology Products in the FDAs Center for Drug Evaluation and Research.

Gilenya, made by Novartis AG, is the first in a new class of drugs that block some blood cells in lymph nodes, reducing their migration to the brain and spinal cord, which may help with reducing the severity of MS.

The drug has also been approved in Russia and is awaiting approval in other countries. Merck is now selling a similar MS drug, cladribine, in Australia and Russia and is expecting approval in the U.S. later this year.

MS is a chronic, often disabling, disease that affects the central nervous systemthe brain, spinal cord, and optic nerves. According to the National Multiple Sclerosis Society, there are about 400,000 people in the United States and 2.1 million people worldwide with MS.

The progress, severity, and specific symptoms of MS are unpredictable and vary from one person to another. Symptoms can be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.

Patients using Gilenya should be monitored for a decrease in heart rate upon starting the drug. Gilenya may also increase the risk of infections. Cases of serious eye problems (macular edema) have occurred in patients taking the drug and an ophthalmologic evaluation is recommended.

The most frequent adverse reactions reported by patients taking Gilenya in clinical trials include headache, influenza, diarrhea, back pain, elevation of certain liver enzymes and cough.

The drug will be available in 0.5 milligram capsules.

Read more about Multiple Sclerosis.

The Food and Drug Administration has licensed a new biologic approach to treat patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of symptom flare-ups or exacerbations of the disease. MS is a chronic, often disabling disease of the brain and spinal cord.

Natalizumab, the new product, is a monoclonal antibody bioengineered from part of a mouse antibody to closely resemble a human antibody. It is being marketed under the tradename Tysabri. The product is given intravenously once a month in a physician's office.

According to the Multiple Sclerosis Association of America, approximately 350,000 individuals have been diagnosed with MS in the U.S., with an estimated 10,000 new cases diagnosed each year. The most common form of MS at the time of initial diagnosis is a relapsing-remitting form, in which acute symptoms or worsening of neurologic function, referred to as "relapses," "attacks," or "exacerbations," occur intermittently. The symptoms can diminish or disappear for months or years between relapses.

Although the cause of MS is unknown, it is widely considered to be an autoimmune disease in which the person's immune system attacks the brain and/or spinal cord. Tysabri appears to work by binding to these immune system cells, thus preventing them from traveling to the brain where they can cause damage.

Antibodies are proteins produced by a person's immune system to fight foreign substances, such as infections. Monoclonal antibodies, such as natalizumab, can be produced in large quantities in cell culture in a laboratory setting. They can be designed to bind to proteins on the body's normal cells. By recognizing and attaching to these proteins, monoclonal antibodies can interfere with (or alter) normal or abnormal cellular responses. In this way, monoclonal antibodies may be useful in the treatment of certain diseases such as MS.

"This innovative treatment for multiple sclerosis represents a new approach to treating MS -- exciting news for patients with this serious disease," said Dr. Lester M. Crawford, Acting FDA Commissioner. "While we eagerly await long-term results from ongoing clinical trials, we have reason to believe that Tysabri will significantly reduce relapses in MS."

The FDA said approval of Tysabri is based on positive results seen in patients after one year of treatment. The agency said the product received accelerated approval because it appears to provide substantial benefit for patients with a serious disease. As part of that approval, the manufacturer has committed to continuing its trials of this product for another year.

Tysabri was evaluated for safety and efficacy in two ongoing randomized, double-blind, placebo-controlled trials in patients with relapsing forms of MS. In the first clinical trial of the product's safety and efficacy, the drug reduced the frequency of relapses by 66 percent relative to placebo.

In a second trial, patients who had been treated with Avonex (interferon beta-1a), an approved treatment for MS, but who had experienced one or more relapses while on Avonex, were randomized to receive Tysabri or placebo. Avonex was continued throughout the study for both groups. In this trial, natalizumab reduced the frequency of relapses by 54 percent relative to placebo.

The most frequently reported serious adverse reactions were infections, including pneumonia, temporary hypersensitivity reactions (such as rash, fever, low blood pressure, and chest pain), depression, and gallstones. These serious adverse reactions were uncommon.

Common adverse reactions were generally mild and included non-serious infections such as urinary tract, lower respiratory tract, GI system, and vaginal infections, headache, depression, joint pains, and menstrual disorders.

Tysabri is marketed by Biogen Idec, Inc., of Cambridge, Massachusetts, and Elan Pharmaceuticals, Inc., of Dublin, Ireland.

Gout occurs due to an excess of the bodily waste uric acid, which is eventually deposited as needle-like crystals in the joints or in soft tissue. These crystals can cause intermittent swelling, redness, heat, pain and stiffness in the joints.

Gout is strongly associated with obesity, high blood pressure, high cholesterol and diabetes, and occurs more often in men, in women after menopause, and in people with kidney disease.

"About three percent of the three million adults who suffer from gout are not helped by conventional therapy. This new drug offers an important new option for them," said Badrul Chowdhury, M.D., director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA's Center for Drug Evaluation and Research.

Metabolizes uric acid

For patients with gout, the conventional therapy is to receive drugs that lower the amount of uric acid in the blood -- for example, the xanthine oxidase inhibitors Zyloprim (allopurinol) and Uloric (febuxostat). Krystexxa is an enzyme that lowers uric acid levels by metabolizing it into a harmless chemical that is excreted in the urine. The drug is administered to patients every two weeks as an intravenous infusion.

Two six-month clinical trials of 212 total patients demonstrated that the drug lowered uric acid levels and reduced deposits of uric acid crystals in joints and soft tissue, the FDA said.

Since one out of every four patients in the clinical trials experienced a severe allergic reaction when receiving an infusion of Krystexxa, health care providers should dispense a corticosteroid and an antihistamine to their patients beforehand to minimize the risk of such a reaction, the agency advised. Other reactions during the clinical trials included gout flare, nausea, injection site bruising, irritation of the nasal passages, constipation, chest pain and vomiting.

Physicians are also being warned to be cautious about administering Krystexxa to patients with congestive heart failure because the drug was not studied in this patient population.

Krystexxa is being approved with a Risk Evaluation and Mitigation Strategy that includes a medication guide for patients and materials for healthcare providers to communicate the risk of severe infusion and allergic reactions. The drug is manufactured by Savient Pharmaceuticals Inc. of East Brunswick, N.J.

Help may soon be on the way for folks who find themselves constantly running for the bathroom. 

The U.S. Food and Drug Administration has approved Myrbetriq (mirabegron) to treat adults with overactive bladder -- a condition in which the bladder muscle cannot be controlled, squeezes too often or squeezes without warning. 

An extended-release tablet taken once daily, Myrbetriq improves the storage capacity of the bladder by relaxing the bladder muscle during filling. Symptoms of overactive bladder include the need to urinate too often (urinary frequency), the need to urinate immediately (urinary urgency) and the involuntary leakage of urine as a result of the need to urinate immediately (urge urinary incontinence). 

“An estimated 33 million Americans suffer from overactive bladder, which is uncomfortable, disrupting and potentially serious,” said Victoria Kusiak, M.D., deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, adding that, the products approval “provides a new treatment option for patients with this debilitating condition.” 

Rigorous testing 

Myrbetriq’s safety and efficacy were demonstrated in three double-blind, placebo-controlled, multicenter clinical trials. A total of 4,116 patients with overactive bladder were randomly assigned to take Myrbetriq at doses of 25 milligrams, 50 mg, 100 mg, or a placebo once daily for 12 weeks. 

Results showed that Myrbetriq 25 mg and 50 mg effectively reduced the number of times a patient urinated and the number of times a patient had wetting accidents during a 24-hour period. Patients taking Myrbetriq 50 mg also expelled a greater amount of urine, demonstrating the drug’s effectiveness in improving the storage capacity of the bladder. 

Side effects 

The most common side effects observed in the trials were increased blood pressure, common cold-like symptoms (nasopharyngitis), urinary tract infection, constipation, fatigue, elevated heart rate (tachycardia) and abdominal pain. 

Myrbetriq is not recommended for use in those with severe uncontrolled high blood pressure, end stage kidney disease or severe liver impairment. 

Myrbetriq is marketed by Astellas Pharma US, Inc. of Northbrook, Ill.

The U.S. Food and Drug Administration (FDA) has approved Marqibo (vincristine sulfate liposome injection) to treat adults with a rare type of leukemia called Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL). 

ALL is a rapidly progressing form of blood and bone marrow cancer that is more commonly diagnosed in children than adults. According to the National Cancer Institute, an estimated 6,050 men and women will be diagnosed with ALL and 1,440 will die from the disease this year. 

Seriously ill 

Marqibo is approved for patients whose leukemia has returned (relapsed) two or more times, or whose leukemia has progressed following two or more regimens of anti-leukemia therapy. Marqibo contains vincristine, a commonly used anti-cancer drug, encased within a liposome, a drug delivery vehicle composed of material similar to that of cell membranes. It is an injection administered once a week by a health care professional. 

“Marqibo’s approval demonstrates the FDA’s commitment to the development and approval of drugs that address serious, unmet medical 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. “Marqibo provides an additional option for Philadelphia chromosome negative acute lymphoblastic leukemia patients whose disease is unresponsive to available therapies.” 

Speedy action 

Marqibo is approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts additional clinical studies to confirm the drug’s clinical benefit and safe use. Marqibo also received orphan-product designation by the FDA because it is intended to treat a rare disease or condition. 

The drug’s effectiveness was evaluated in a single clinical trial in adult patients whose leukemia had relapsed at least two times despite standard treatments, and who had at least one previous treatment response lasting at least 90 days. The study objective was to determine the response rate to Marqibo, as either a complete remission (CR) or a complete remission with incomplete blood count recovery (CRi). Of 65 patients enrolled, 10 patients, or 15.4 percent, responded with either a CR or CRi. In the 10 patients achieving CR or CRi, the median duration of documented remission was 28 days. The median time to the first event of relapse, death, or next therapy was 56 days. 

The safety of Marqibo was evaluated in two single-arm trials of 83 patients who received the clinical treatment regimen. Serious adverse events such as low white blood cell counts with fever, low blood pressure, respiratory distress and cardiac arrest occurred in 76 percent of the patients studied. The most common side effects observed during clinical studies include constipation, nausea, low blood cell counts, fever, nerve damage, fatigue, diarrhea, decreased appetite, and insomnia. 

Prescription warning 

Prescribing information for Marqibo will carry a Boxed Warning alerting patients and health care professionals that the drug must be administered only through a vein (intravenously) because it is deadly if administered in other ways, such as into the spinal fluid. 

The Boxed Warning also states that Marqibo has different dosage recommendations than vincristine sulfate injection alone. To avoid overdose, it is important for health care professionals to verify the drug name and the dose before administration. Special requirements for preparation of the drug are detailed in the label.