Xolair (omalizumab) is an injectable asthma medication produced by a Chinese hamster ovary cell suspension culture containing the antibiotic gentamicin, which is not detectable in the final product. The drug comes in a “freeze-dried” (lyophilized) powder form and is mixed with sterile water and administered via a shot (subcutaneous injection) to the patient. Since its inception in 2003, Xolair has been used to treat more than 200,000 patients with a type of asthma caused by allergens (allergic asthma) and a chronic type of hives with no identifiable cause (chronic idiopathic urticaria, or CIU).
Clinical trials prior to Xolair’s release onto the market excluded patients who smoke or were using controller medications other than inhaled corticosteroids or short-acting beta2-agonists, such as albuterol used for asthma attacks. While initially approved by the U.S. Food and Drug Administration for use in children aged 12 to 17 and adults, Novartis Pharmaceuticals Corporation, working alongside Genentech USA, Inc. in the manufacture and marketing of the medication, announced in mid-2016 that the FDA had expanded the age range for Xolair to include children aged six to 11.
Did You Know
Xolair the first-and-only approved biologic for pediatric patients six years of age and older.
The company reported that the approval came three months ahead of the FDA action date, making Xolair the first-and-only approved biologic (medication manufactured in a living system such as a microorganism, or plant or animal cells, mostly using recombinant DNA technology) for pediatric patients six years of age and older with uncontrolled moderate to severe persistent allergic asthma.
But post-marketing reports surfaced regarding a potential for Xolair to result in a severe, life-threatening allergic reaction called anaphylaxis. This new information required a label change and the inclusion of a black box warning in 2007, advising patients and physicians that anaphylaxis could occur at any time after taking Xolair, whether it’s after the first dose or even following a year or more of treatment with no prior reactions. It was also recommended that patients be monitored by a health care professional for an amount of time after receiving an injection since anaphylaxis was not always found to occur immediately after treatment with Xolair.
Then in 2009, the FDA began an evaluation of an ongoing safety study that showed that patients being treated with Xolair were at an increased risk of heart and brain blood vessel problems. The observational study, titled Evaluating the Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma (EXCELS), included approximately 5,000 Xolair patients as well as a control group of approximately 2,500 non-Xolair patients.
Weaknesses in the FDA’s safety study disallowed the federal agency to definitively confirm or determine the exact increased level of risks involving heart and brain blood vessels.
In 2014, the FDA finally announced the results of the five-year study, concluding that while a higher risk to Xolair patients of experiencing certain adverse events involving the heart and brain blood vessels was found, certain weaknesses in the design and implementation of the safety study disallows the federal agency to “definitively confirm or determine the exact increased level of these risks.”
The same conclusion was determined for a showing of a slightly higher rate of Xolair patients acquiring various cancers in comparison to non-Xolair patients. As a result of limitations in the five-year safety study, the FDA was unable to “rule out a potential risk of cancer with Xolair,” necessitating further label changes to warn patients and physicians of both an increased risk of heart and brain blood vessel problems for patients treated with Xolair as well as the potential for an increased risk of cancer.
What Does Xolair Treat?
Xolair (omalizumab) is indicated for the treatment of moderate to severe persistent asthma, resulting from allergies (allergic asthma), in individuals of age six and older, whose symptoms cannot be adequately controlled with inhaled corticosteroids (a type of steroid similar to hormones made by a person’s adrenal glands to fight stress and reduce inflammation).
While the symptoms of asthma and allergic asthma are the same, the triggers are different. Having allergic asthma means that allergens, or year-round exposure to certain elements resulting in an allergic response, are the cause of a person’s asthma symptoms. Allergens are substances that cause an allergic reaction because the immune system thinks they are harmful.
The immune system attacks the perceived foreign and harmful agent by releasing a substance called immunoglobulin E (or IgE). Too much of this substance can cause inflammation (swelling) in the body and in the airways in a person’s lungs. As the condition worsens, it can become difficult to breathe and may even result in an asthma attack.
People with allergic asthma often have higher levels of IgE present in their bodies because of their immune system response to allergens. Blocking the release of IgE may then be a part of an individual’s treatment plan if they suffer from allergic asthma.
Xolair is also used for the treatment of chronic idiopathic urticaria (CIU) in patients 12 years of age and older, who have persistent symptoms (hives) despite treatment with a H1-antihistamine, or histamine blocker at the H1 receptor (anti-allergy drugs).
Xolair should not be used to treat other allergic conditions, including other forms of urticaria. It is also not approved for the treatment of severe asthma attacks or airway constrictions, such as acute bronchospasm and status asthmaticus.
What Is Asthma?
Asthma is a chronic disease that affects a person’s airways, causing them to swell and narrow. Your airways are tubes that carry air in and out of your lungs. When the inside walls of these airways become sore and swollen, they also become very sensitive causing them to react strongly to allergens (substances that cause allergic reactions) and other irritants. As the airways react and continue to narrow, less air can get through to your lungs.
Common asthma triggers include:
- Animals (pet hair or dander)
- Changes in weather (usually colder temperatures)
- Strong emotions or stress
- Dust mites
- Certain medications (such as aspirin and other NSAIDs)
- Chemicals in the air or food
- Respiratory infections (such as the common cold)
- Tobacco smoke
Asthma can lead to symptoms such as wheezing (a whistling sound when you breathe), coughing (especially early in the morning or at night), chest tightness and shortness of breath. If symptoms of asthma worsen, it’s called an asthma attack. Severe asthma attacks may require emergency care and can even be life-threatening.
Asthma affects people of all ages, but it most often begins in childhood. In the United States, more than 25 million people are living with asthma, and approximately seven million of those people are children. There is no cure for asthma, but it can be managed with quick-relief and long-term medications, and symptoms can sometimes improve over time.
What Is Chronic Idiopathic Urticaria (CIU)?
Urticaria is the medical term for hives, which are red and often itchy, sometimes painful, bumps on the skin that are usually caused by an allergic reaction to a drug or food. During an allergic reaction, the body releases chemicals called histamines that can make the skin swell into hives. Other than an allergic response, hives can be caused by other conditions such as infections, stress and certain autoimmune conditions.
When hives last for six weeks or longer, the condition is considered chronic. In about three out of 10 cases, the cause of hives is known; but in another seven out of 10 cases of chronic hives, a cause cannot be determined. This is diagnosed as chronic idiopathic urticaria (CIU), and it is the most common type of chronic hives, mostly occurring between the ages of 20 and 40. Women are more likely than men to have CIU, experiencing flares that last anywhere from one to five years or longer.
In rare cases, hives can cause swelling in a person’s airways making it difficult to breathe and requiring emergency treatment. If not immediately treated, this dangerous occurrence can even result in death.
How Is Xolair Administered?
Xolair is an injectable prescription medicine administered by a health care provider in a health care setting. It is a subcutaneous injection, meaning it is given in the fatty layer of tissue just under the skin. Subcutaneous injection sites can include the upper arms, abdomen in the belly area and front of the thighs.
The National Institutes of Health (NIH) advises rotating injection sites to keep the skin healthy, as repeated injections in the same location can cause scarring and hardening of tissues that can interfere with subsequent administration and absorption of medication.
Xolair is administered in dosages of 150 milligrams to 375 milligrams every two to four weeks. Dosing and dosing frequency is measured prior to the start of treatment and determined by total pre-treatment blood serum levels of IgE and body weight. A patient’s physician should periodically reassess the need for continued treatment based on the severity of the disease and overall management of their asthma symptoms.
Doses should be adjusted for any significant changes in body weight when receiving Xolair for the treatment of allergic asthma.
When receiving Xolair for the treatment of allergic asthma, doses should be adjusted for any significant changes in body weight. Re-testing of IgE levels during treatment cannot be used as a guide for subsequent dose determinations and adjustments, due to the fact that total IgE levels are elevated as a result of treatment and will remain elevated for up to one year following the discontinuation of the asthma medication.
Dosing of Xolair in patients being treated for CIU is not determined on serum IgE levels or body weight. Rather, treatments should be administered by subcutaneous injection every four weeks in dosages of 150 milligrams or 300 milligrams. A patient’s physician should periodically reassess the need for continued treatment as the appropriate duration of Xolair therapy for CIU has not yet been evaluated.
Xolair injections take approximately five to ten seconds to administer due to the consistency of the solution being slightly viscous (thick and sticky). Each vial delivers 150 milligrams, or 1.2 milliliters of medication per injection site. If more than 150 milligrams is required for treatment, the doses need to be divided among two or more injection sites.
Studies have not yet determined the maximum tolerated dose of Xolair. When administering single doses of up to 4,000 milligrams to patients, no toxicity was found to have resulted. The highest cumulative dose administered to patients was 44,000 milligrams over a 20-week period with no adverse events or resulting toxicity associated with the higher dosing amount.
Side Effects of Xolair
Xolair is not without side effects, ranging from mild to severe, and even life-threatening. Post-marketing reports showed that a severe allergic reaction called anaphylaxis can occur after receiving Xolair, following just one dose or many doses. It can also occur immediately after receiving the injection, or days later. If not immediately treated, anaphylaxis can be deadly. Additionally, a five-year safety study evaluated by the FDA found that patients who received Xolair injections had a slightly increased risk of problems involving the heart and blood vessels in the brain.
These problems included:
- Mini-strokes (known as transient ischemic attacks, or TIAs)
- High blood pressure in the arteries of the lungs (called pulmonary hypertension)
- Heart attacks
- Sudden, unexpected chest pain
- Blood clots in the lungs and veins
Other common side effects of Xolair include:
- Pain, especially in the arms and legs
- Feeling tired
- Bone fractures
- Skin rash
- Pain or discomfort of the ears
Pediatric patients (ages six to 12) may experience slightly different side effects, including common cold symptoms, headache, fever, sore throat, earache or ear infection, abdominal pain, nausea, vomiting and nose bleeds.
Side effects in patients who are being treated for CIU:
- Swelling of the inside of your nose, throat or sinuses
- Joint pain
- Upper respiratory tract infection
Injection site reactions include swelling, erythema (redness of the skin caused by increased blood flow in the capillaries in the lower layers of skin), pain, itching, bleeding and hives.
Serious side effects of Xolair include:
- Cancer — Patients receiving Xolair may have a higher risk of certain types of cancer.
- Inflammation of blood vessels — Symptoms include chest pain, shortness of breath, or a feeling of pins and needles or numbness of the arms and legs.
- Fever, muscle aches and rash — These symptoms can occur one to five days after receiving Xolair.
- Parasitic infection — This side effect can occur after receiving Xolair in patients who are at high-risk for parasite (worm) infections.
- High blood levels of a certain antibody (serum total IgE)
Black Box Warning: Anaphylaxis
In July 2007, the U.S. Food and Drug Administration announced that Genentech updated its labeling for Xolair to include a boxed warning, often referred to as a black box warning. The FDA requested the change following new post-marketing reports that anaphylaxis was occurring after administration of the injectable asthma drug. In a FDA news bulletin, the FDA was reported as saying it requested the labeling change “because of the continued reports of anaphylaxis and the life-threatening potential of its delayed onset.”
According to the National Institutes of Health (NIH), anaphylaxis is “a severe, whole-body allergic reaction to a chemical that has become an allergen.” It is an emergency condition that requires immediate medical attention. Without treatment, anaphylaxis can result in blocked airways, cardiac arrest (stopping of the heart), respiratory arrest (no breathing) or shock.
Symptoms of an anaphylaxis reaction can include:
- Trouble breathing
- Chest tightness
- Dizziness or lightheadedness
- Nausea or vomiting
- Difficulty swallowing
- Itching and hives
- Swelling of the, face, eyes, mouth, tongue and throat
- Abdominal pain
- Feeling anxious
- Low blood pressure
- Flushing or feeling warm
- Slurred speech
In previous clinical trials for Xolair that included 39,500 human test subjects, it was determined that anaphylaxis occurred in as little as 0.1 percent of patients, typically within one to two hours of receiving a subcutaneous injection of the medication.
But new reports indicated that anaphylaxis was delayed in some patients, sometimes for more than 24 hours following a Xolair treatment. While this result can occur as early as after the first dose of Xolair, it was also found to occur after any dose of the asthma medication even beyond one year of beginning regular treatment on Xolair, and even if there was no adverse reaction to previous doses.
FDA Safety Communication: Risk for Heart and Brain Problems
In July 2009, the FDA announced it was evaluating interim safety findings from an ongoing study of Xolair that suggested an increased number of heart and brain complications and other potential adverse events in patients being treated with Xolair. ABC News reported that the FDA began its review following reports of “an increased risk of heart attack, abnormal heart rhythm, heart failure and stroke.”
The study, titled Evaluating the Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma (EXCELS), was an observational study that spanned five years. It included 5,000 patients being treated with Xolair and a control group of 2,500 non-Xolair users. Even though early results of the study provoked the federal agency’s investigation, finding that Xolair users were at a higher risk for heart problems compared to nonusers, the FDA did not recommend any changes to prescribing information at that time or that patients stop taking Xolair.
The FDA found that Xolair users were at a higher risk for heart problems compared to nonusers.
In September 2014, the FDA released a safety announcement following its review of the five-year safety study. The federal agency reported that results showed a “slightly higher rate of heart and brain blood vessel problems” in the patients being treated with Xolair compared to those who were not treated with the asthma medication. The FDA concluded, “Although the data are suggestive of a serious safety signal, due to weaknesses in how the safety study was designed and carried out, we are unable to definitively confirm or determine the exact increased level of these risks with Xolair.”
The FDA furthered its evaluation of the EXCELS results by reviewing a combined analysis of 25 randomized double-blind clinical trials comparing Xolair to a placebo (dummy pill). Although these trials did not come to the same conclusion, the FDA noted that trial conditions such as the low number of these events, the young patient population and the short duration of follow-up would not allow for any “definite conclusions” about the absence of a risk.
While the agency stopped short of requiring Genentech and Novartis to issue a black box warning, this new information did necessitate changes to the “Adverse Reactions” section of the drug label.
The FDA noted in the same 2014 safety communication that previous clinical trials also showed “slightly higher rates of various cancers” in patients treated with Xolair versus nonusers. The FDA pointed out that its review of the five-year study found no difference in cancer rates among Xolair users and those not treated with Xolair, but the agency also said that due to limitations in the study a potential risk of cancer cannot be ruled out. Therefore, the FDA required this information to also be added to the “Warnings and Precautions” section as a part of the drug label changes.
Did You Know
No formal drug interaction studies have been performed with Xolair.
No formal drug interaction studies have been performed with Xolair. In patients with allergic asthma, the associated use of Xolair and allergen immunotherapy (commonly referred to as allergy shots) has not been evaluated. Similarly, it is unknown what interactions might occur in patients with CIU using Xolair and other immunosuppressive therapies simultaneously.
Adequate and well-controlled studies in pregnant women using Xolair have not been conducted, and therefore, the data is insufficient to inform patients on associated risk. Likewise, for breastfeeding mothers, it is unknown if Xolair is present in breast milk.
In 2006, 2010 and 2012, Genentech and Novartis were hit with whistleblower, or qui tam, actions filed by Frank Garcia, Stephen Fauci and Allison Kelly, respectively, all former employees of the drug companies. In a qui tam case, a private party called a relator brings an action on behalf of the government. In this regard, the government is considered the real plaintiff to the lawsuit. If the government prevails in the suit, the relator (or relators) receive a portion of the award.
The federal False Claims Act allows for relators to bring qui tam actions against parties who have defrauded the federal government. In these suits, the relators all alleged that Genentech and Novartis engaged in off-label marketing (including urging health care professionals to use Xolair for children, active asthma and other allergic conditions not related to asthma, such as peanut allergies), and kickback schemes in the form of free cash equivalents and expensive gifts, free medical and office equipment, and free services to health care providers to induce them to prescribe Xolair in an effort “to broaden their patient population and increase sales.” The relators claimed that the pharmaceutical companies engaged in these actions despite the FDA’s approval for “limited uses.”
The relators also claimed that the drug companies’ efforts were successful, driving sales from $25 million in Xolair’s first year on the market to $320 million in just two years’ time. From its onset in 2003 to 2008, Xolair sales in the United States had increased by approximately $2 billion.
Plaintiffs claimed that the manufacturers misbranded Xolair, making it ineligible for reimbursement under government health care programs.
The relators further claimed that Genentech and Novartis had misbranded Xolair “making it ineligible for reimbursement” under government health care programs, such as Medicare and Medicaid. Additionally, the relators claimed that health care providers were induced to submit claims for reimbursement at improper rates by using improper medical codes, called upcoding, for the administration of Xolair.
But on June 17, 2016, despite the allegations, the U.S. Court of Appeals affirmed a district court’s ruling to dismiss the federal claims with prejudice (meaning they cannot be amended, revised and refiled), finding that the relators failed to state their complaints with “sufficient particularity” (not clearly enough), and that the lower court did not abuse its discretion in denying the relators the opportunity to amend their complaints.
However, as to the legal claims made at the state level, the appeals court found that the district court failed to exercise jurisdiction (or the official power to make legal decisions and judgments) over them prior to also dismissing those claims. The appeals court therefore vacated (or got rid of) that ruling with instructions for the district court to dismiss the state-law claims without prejudice, providing the relators the opportunity to amend and refile those claims.
Potential for Personal Injury Claims
With former employees accusing Genentech and Novartis of wrongdoing in the marketing and sales of Xolair, and with post-marketing studies and reports linking the use of Xolair to serious
Future Claims Incoming
Drug companies are likely to face lawsuits stemming from personal injury claims made by injured patients using Xolair.
side effects, such as life-threatening anaphylaxis, heart attacks, mini-strokes, blood clots in the lungs, high blood pressure in the arteries of the lungs, and possibly even cancer, the drug companies are likely to face lawsuits stemming from personal injury claims made by injured patients using Xolair.
Law firms across the country are currently seeking out injured consumers and preparing to file lawsuits on behalf of patients who have suffered serious side effects or even death after receiving Xolair treatments.
Kristin Compton is a medical writer with a background in legal studies. She has experience working in law firms as a paralegal and legal writer. She also has worked in journalism and marketing. She’s published numerous articles in a northwest Florida-based newspaper and lifestyle/entertainment magazine, as well as worked as a ghost writer on blog posts published online by a Central Florida law firm in the health law niche. As a patient herself, and an advocate, Kristin is passionate about “being a voice” for others.
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