FDA Drug Approvals

The U.S. Food and Drug Administration (FDA) thinks seven companies have gone too far in claiming that their dietary supplements can cure, treat, mitigate or prevent cardiovascular disease or related conditions, such as atherosclerosis, stroke or heart failure.

The FDA is making an all-out plea to consumers to stop using these – or similar products – because they haven’t been cleared by the agency as safe or effective for their intended use and may be harmful.

The warning letters were issued to: Essential Elements; Calroy Health Sciences; Iwi; BergaMet North America; Healthy Trends Worldwide (Golden After 50); Chambers' Apothecary; and Anabolic Laboratories. Those manufacturers market a variety of products tied to cardiovascular disease, et al, such as CoEnzyme Q10 and Cholesterol Command.

Dear sir, please stop what you’re doing… now

When ConsumerAffairs reviewed the letter sent to the various companies, it was clear that the FDA was nowhere near happy about how far those supplement producers had gone to convince the unaware consumer that their products were the end-all and be-all.

For example, in its letter to Healthy Trends Worldwide, the maker of Golden After 50 products, the company’s pitch of “That’s why we combined five science-backed ingredients from nature that address multiple factors to help regulate blood pressure” was labeled a false claim.

As was pushing its products’ agenda on YouTube videos where a spokesperson said that ingredients of its BP-5 formula “can lower your high blood pressure naturally and fast.”

“Your BPS-5 product is not generally recognized as safe and effective for the above referenced uses and, therefore, this product is a “new drug” … [adding] “new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA. FDA approves a new drug on the basis of scientific data and information demonstrating that the drug is safe and effective," the letter stated.

What’s so bad about dietary supplements, anyway?

The FDA isn’t criticizing dietary supplements in general. It feels that some can help a person improve their health or help meet the daily requirements of essential nutrients. What it’s unhappy about is that companies are promise-bombing the internet with unfounded claims.

“Given that cardiovascular disease is the leading cause of death in the U.S., it’s important that the FDA protect the public from products and companies that make unlawful claims to treat it,” said Cara Welch, director of the Office of Dietary Supplement Programs in the FDA’s Center for Food Safety and Applied Nutrition. 

And, yes, dietary supplements have to pass the approval of the agency just like a doctor-prescribed drug does.

Fortunately, the seven companies receiving those letters haven’t been served an order to shut down, but rather a request to address the agency’s concerns – what the proper dosage might be, how they could interact with FDA-approved drugs or other substances, or whether they have dangerous side effects or other safety concerns.

“Dietary supplements that claim to cure, treat, mitigate or prevent cardiovascular disease and related conditions could potentially harm consumers who use these products instead of seeking safe and effective FDA-approved treatments from qualified health care providers. We encourage consumers to remain vigilant when shopping online or in stores to avoid purchasing products that could put their health at risk,” Welch said.

For a complete list of FAQs and questions to ask physicians and pharmacists regarding dietary supplements, the FDA offers a consumer guide here.

Earlier this week, the U.S. Food and Drug Administration (FDA) approved a new oral treatment for consumers who suffer from acute migraines.

The drug, named Ubrelvy, is manufactured by Allergan and meant to be taken after symptoms of a migraine have already begun to set in. The FDA said the drug was proven to be more effective than placebos in two randomized, double-blind trials. 

“The FDA is pleased to approve a novel treatment for patients suffering from migraine and will continue to work with stakeholders to promote the development of new safe and effective migraine therapies,” said FDA director Dr. Billy Dunn.

Many participants who took Ubrelvy in the drug trials reported feeling no pain or other associated migraine symptoms after two hours. Regulators said the results are promising for treating a serious health condition that affects millions of people.

“Migraine is an often disabling condition that affects an estimated 37 million people in the U.S. Ubrevly represents an important new option for the acute treatment of migraine in adults, as it is the first drug in its class approved for this indication,” said Dunn. 

The Food and Drug Administration (FDA) has approved a new generic version of the blood pressure drug valsartan, which is also sold under the trade name Diovan. Valsartan is a widely used angiotensin II receptor blocker (ARB) that doctors prescribe for high blood pressure and heart failure.

The approval was placed on the FDA fast track after the agency confirmed the presence of an impurity in several lots of the medicine last year. Researchers detected a trace amount of an unexpected impurity -- N-nitrosodimethylamine (NDMA). NDMA has been classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC).

The discovery led to major recalls of existing forms of valsartan, which in turn led to shortages of the drug.

“To address the public health consequences of these shortages, we've prioritized the review of generic applications for these valsartan products,” said FDA Commissioner Scott Gottlieb. “When faced with a drug shortage situation, the FDA employs a number of strategies to help mitigate the effects of the shortage on patients. As part of that work, we look at where we may be able to prioritize review of pending generic applications of the medicine in shortage, or similar products.”

Gottlieb said he is hopeful the approval of the new generic will quickly alleviate the valsartan shortage. Meanwhile, he says the FDA will step up its efforts to keep impurities out of approved prescription drugs.

Suspected human carcinogen

Valsartan began disappearing from pharmacies in the middle of last year after a Chinese company reported the presence of NDEA in several batches of its valsartan API. It was of special concern since NDEA is a suspected human carcinogen.

The FDA began its tests after the Chinese report and resulting recalls. The FDA probe, completed in September, not only found the impurity in the Chinese company's product, but also in Torrent Pharmaceutical’s valsartan 160mg (lot BV47D001) and 320mg (lots BV48D001 and BV48D002) tablets.

The discovery of a potential carcinogen in a prescription drug may well have been a wakeup call for the agency, It says it has conducted a major investigation to address the presence of nitrosamine impurities in certain generic ARB products.

The FDA says it has also worked with companies to move quickly to remove any products with unacceptable impurities from the U.S. market.

Mrs. Thomas took her prescription for her heart medication to the pharmacy to have it filled. “I don’t want one of those generic drugs either,” she stated. “I want the real thing.” So, are brand name drugs really better than generic version?

According to recent information published in Consumer Reports, the answer is an emphatic no. To win approval from the Food and Drug Administration (FDA), the manufacturer of the generic medication must show that the drug has the same active ingredient and that it is identical in strength, dosage form, route of administration and labeling as the brand name drug.

The company must also demonstrate that individuals absorb and excrete the medication at the same rate. Says a pharmaceutical scientist who worked for decades at the FDA, “People may think that brand name products are better because they’re more expensive, but the body doesn’t know whether the drug came from a brand name or a generic company.”

When a medication goes off patient, other pharmaceutical manufacturers are free to create generic versions of that drug. The consumer can save considerable money by switching to the generic form of that drug. But the price of the drug does not go down immediately after the generic is released to the market.

Let’s take a mythical medication, Fat-no-more, used for weight loss, as an example. The brand’s retail price for a month’s worth of Fat-no-more is $220. Then it goes generic. After one year, the generic price is about half: $110. After 2 years on the market, it goes to $48. After 3 years, the price is $12.

Why does it take so long for the price to go down? When a drug is about to go off patent, manufacturers file lawsuits to challenge the patent. The company that wins obtains a 6-month period to sell that generic exclusively. When that period is over, other generic houses can produce that drug, forcing the prices even lower. Today, 8 out of 10 prescriptions filled in the US are for generic drugs, says the FDA. Cost is a big factor because generics can be as much as 85% cheaper than their brand counterparts.

Costs soaring

The cost of generic drugs is soaring, however.

Relatively cheap as they are compared with brand name products, the price gap between brand name drugs and generics is beginning to narrow – and it is not because proprietary drugs are getting cheaper. A 2014 article in the New England Journal of Medicine revealed that certain older drugs, many of which are generic and not protected by patents or market exclusivity, are now also extremely expensive.

Examples:

• Captopril, used for hypertension and heart failure, increased in price by more than 2,800% between November 2012 and November 2013, from 1.4 cents to 39.9 cents per tablet.
• Doxycycline, a broad-spectrum antibiotic that has been in existence since 1967, zoomed in price from 6.3 cents to $3.36 per pill.
• Clomipramine, a long-established antidepressant, has jumped in price from 22 cents to $8.32 per pill.
• Digoxin, used for atrial fibrillation (irregular heartbeat) and heart failure by millions of Americans, saw a price increase of 637% between 2002 and 2013.
• Some generic versions of codeine formulations for migraine, thyroid medicines, as well as the generic steroid prednisolone, have all more than doubled in price since last year, according to industry analyst EvaluatePharma. 

Yet, low-cost generics have saved the health care industry $209 billion in 2012, $239 billion in 2013 and almost $1.5 trillion over the past decade, according to the most recent data.

Sadly, prices have spiked for certain medications because of shortages of raw materials, supply disruptions or other factors that have led some manufacturers to stop producing those medications, resulting in a near monopoly. The number of manufacturers of digoxin, for example, has fallen from 8 to 3.

As Aaron Kesselheim, MD, assistant professor of pharmaceutical economics at Harvard Medical School, stated, “Studies show it is not until you have 4 or 5 companies manufacturing the same generic will the prices really drop.” Therefore, ask your doctor to switch your medications to another drug in that class if you are spending more money than you would like.

Mrs. Thomas’ pharmacist explained the generic process to her and she agreed that perhaps the generic form of her pricy heart medication was as good as the “real thing” and she agreed to switch to the generic. She was pleased at the money she saved, as well as the confidence she gained from her pharmacist’s counseling.

The FDA has moved levonorgestrel – the contraceptive drug first sold as “Plan B One-Step” – one step closer to full over-the-counter status, by removing previous legal restrictions limiting the purchase of generic versions to buyers age 17 or older unless the buyers had a prescription.

Plan B's previous legal status was that official name-brand Plan B, produced by Teva, was available to all ages without a prescription, but the cheaper generic version was prescription-only to those age 16 and younger. The FDA's official reasoning for this restriction was that the generic version still needed to be tested on teenagers (rather than protecting Teva from low-priced generic competition).

NPR's health blog noted on March 2 that “the FDA now says the generic versions of the product must still say on their labels that they are intended for 'women 17 years of age or older,' but they may be sold directly from retail shelves without a requirement to produce proof of age.”

The Reproductive Health Technologies Project praised the FDA decision in a press release (.pdf) which noted that “in the very near future, people seeking generic emergency contraception, which tends to cost $7 less on average than the brand name product, will be able to get it directly off the shelf instead of from a pharmacist. Moving generic products to the shelf will also hopefully result in market competition that will drive down the price of EC overall.”

The FDA decision was made in compliance with a circa-2013 federal court order (also in .pdf form) requiring all “levonorgestrel-based emergency contraceptives [be] available without a prescription and without point-of-sale or age restrictions.”

The first generic versions of Cymbalta (duloxetine delayed-release capsules), a prescription medicine used to treat depression and other conditions, has been green-lighted by the federal government.

The U.S. Food and Drug Administration (FDA) has given approval to

Aurobindo Pharma Ltd., Dr. Reddy’s Laboratories Ltd., Lupin Ltd., Sun Pharma Global FZE, Teva Pharmaceuticals USA, and Torrent Pharmaceuticals Ltd. to market the drug in various strengths.

“Health care professionals and consumers can be assured that these FDA-approved generic drugs have met our rigorous standards,” said Kathleen Uhl, M.D., acting director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research. “Generic drugs offer greater access to health care for many people.”

Boxed warning

Duloxetine and other antidepressant drugs have a boxed warning describing the increased risk of suicidal thinking and behavior during initial treatment in children, adolescents and young adults ages 18 to 24. The warning also says data do not show this increased risk in those older than 24 years and that patients ages 65 and older who take antidepressants have a decreased risk of suicidal thinking and behavior.

The warning says depression and other serious psychiatric disorders themselves are the most important causes of suicide and that close monitoring of patients starting these medications is necessary. Duloxetine must be dispensed with a patient medication guide that describes important information about the drug’s uses and risks.

Common adverse reactions reported by people taking Cymbalta include nausea, dry mouth, drowsiness, fatigue, decreased appetite, increased sweating, and dizziness.

Generic prescription drugs approved by the FDA have the same high quality and strength as brand-name drugs. Generic prescription drug manufacturing and packaging sites must pass the same quality standards as those of brand-name drugs.

Depression is characterized by symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy once-pleasurable activities. Episodes often recur throughout a person's lifetime.

Signs and symptoms of depression include: depressed mood, loss of interest in usual activities, significant change in weight or appetite, insomnia or excessive sleeping (hypersomnia), restlessness/pacing (psychomotor agitation), increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration and suicide attempts or thoughts of suicide.

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.

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.

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.

If you use the antibiotic azithromycin, which is sold as Zithromax or Z-Pak, you should know that it can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.

The U.S. Food and Drug Administration (FDA) says patients at particular risk for developing this condition include those with known risk factors such as existing prolongation of the QT interval -- a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, low blood levels of potassium or magnesium, a slower than normal heart rate, or use of certain drugs used to treat abnormal heart rhythms, or arrhythmias.

The FDA advisory follows a review of a study by medical researchers as well as another study by a manufacturer of the drug that assessed the potential for it to cause abnormal changes in the electrical activity of the heart.

Updated labels

The azithromycin drug labels have been updated to strengthen the Warnings and Precautions section with information related to the risk of QT interval prolongation and torsades de pointes, a specific, rare heart rhythm abnormality. Information has also been added regarding the results of a clinical QT study which showed that azithromycin can prolong the QTc interval.

Health care professionals are advised to consider the risk of fatal heart rhythms with azithromycin when considering treatment options for patients who are already at risk for cardiovascular events .

Antibacterial drugs

FDA notes that the potential risk of QT prolongation with azithromycin should be placed in appropriate context when choosing an antibacterial drug: Alternative drugs in the macrolide class, or non-macrolides such as the fluoroquinolones, also have the potential for QT prolongation or other significant side effects that should be considered when choosing an antibacterial drug.

FDA released a statement on May 17, 2012, about a New England Journal of Medicine (NEJM) study that compared the risks of cardiovascular death in patients treated with the antibacterial drugs azithromycin, amoxicillin, ciprofloxacin (Cipro), and levofloxacin (Levaquin), or no antibacterial drug.

The study reported an increase in cardiovascular deaths, and in the risk of death from any cause, in persons treated with a 5-day course of azithromycin (Zithromax) compared with persons treated with amoxicillin, ciprofloxacin, or no drug. The risks of cardiovascular death associated with levofloxacin treatment were similar to those associated with azithromycin treatment.    

Chances are you've done this before: You go to your local pharmacy to buy medicine. You're inclined to go with the familiar brand name product -- the one you've seen in the TV commercials and other ads. But you see the generic version -- which is much less expensive -- and you think, "If it's so inexpensive, it must not be as effective or safe.”

You would be wrong -- and you're not alone.

Food and Drug Administration (FDA) pharmacist Brenda Stodart, Pharm.D., who for 14 years has answered questions on FDA's Drug Information line (1-855-543-DRUG ) says, "Every day without fail we educate consumers and health care professionals about the safety and efficacy of generic drugs."

So, what are generic drugs and how does FDA ensure they are a safe and effective alternative to name brands?

When a new, FDA-approved drug goes on the market, it may have patent or exclusivity protection that lets the manufacturer sell the drug exclusively for a period of time. When those expire or no longer serve as a barrier to approval, other companies can make it in generic form. FDA must approve the generic drug before it can be marketed.

Rigorous standards

Lawrence Yu, Ph.D., FDA acting deputy director for science in FDA's Office of Generic Drugs, explains that for a generic drug to be approved by FDA, its manufacturer must show that it is "equivalent" to the innovator drug (brand name). This means that to gain FDA approval, a generic drug must:

• contain the same active ingredients as the innovator drug. Active ingredients make the drug effective against the disease or condition it is treating.
• come in the same dosage form. If the brand name is a capsule, the generic should be a capsule, too.
• be administered the same way. If the brand name is taken orally, the generic should be taken orally, too.
• be identical in strength
• have the same conditions of use
• be bioequivalent (an equal rate and extent of drug absorbed the bloodstream)
• meet the same standards for identity, strength, purity and quality
• be manufactured under the same standards that FDA requires for the manufacture of innovator products

"Then, and only then,” says Yu, “we can assure consumers that the generic will work as well as the name brand."

Mansoor Khan, R.Ph., Ph.D., the agency's director of the Division of Product Quality Research, says the review process includes a review of scientific data on the drug's manufacturing, ingredients and performance.

Shifting gears

Sometimes, new reports or evidence arise indicating that a generic drug may not have the same safety or effectiveness as was previously believed. "If we have reasons to believe a generic drug does not perform the same as a brand name product," Khan says, "we have the ability to perform experiments in the FDA laboratories and take a comprehensive, scientific look at the differences between the products."

This happened with the generic drug Budeprion XL 300 mg, a generic form of Wellbutrin, a drug used to treat depression. FDA's original bioequivalence evaluation had been of a lower dosage (150 mg). After receiving reports of adverse effects from consumers who used Budeprion at the 300 mg dosage level, the FDA conducted another study and determined that Budeprion XL 300 mg was not bioequivalent to the Wellbutrin XL 300 mg.

FDA requested that the manufacturers of Budeprion XL voluntarily withdraw the 300-mg version from the market, which they promptly agreed to do.

While FDA goes to great lengths to ensure that the brand and generic drugs perform equally, in very rare instances, such as Budeprion XL, these efforts do not succeed. BudeprionXL is definitely an outlier, however, Khan says, as there are literally thousands of approved generic products that perform equally without problems or reports of issues.

The price is right

Generic manufacturers are able to sell their products for lower prices because they are not required to develop a new drug from scratch with pre-clinical studies or to repeat the many costly clinical trials of new drugs, Khan says. Generally, they also do not pay for costly advertising, marketing and promotion.

The Congressional Budget Office estimated that from 1984 to 1994, generic drugs save consumers an estimated $8 to $10 billion a year at retail pharmacies. Even more billions are saved when hospitals use generics.

Even greater savings were found in a report from the IMS Institute for Health Care Informatics commissioned by the Generic Pharmaceutical Association in 2012. It found that generic drugs have saved over $1 trillion over the last decade, $193 billion in 2011 alone.

But not every drug has a comparable generic.

To find out if there is a generic equivalent for your brand-name drug, use Drugs@FDA. You can also search for generic equivalents by using FDA's "Electronic Orange Book." You can also consult the most recent monthly approvals for "First Generics."

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.

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 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.