Over a Decade in the Making

“I called myself a ‘closet asthmatic’ because I tried not to let anyone see how bad my allergic asthma symptoms were.”

Rosemary, a registered nurse in Texas, has had allergic asthma since she was young.

Rosemary, a registered nurse in Texas, has had allergic asthma since she was young. As a child, she was constantly armed with an inhaler, and prescribed inhaled corticosteroids and other medications. Despite those treatments, her allergic asthma was uncontrolled. “I experienced symptoms of wheezing and difficulty breathing. Often I felt like I couldn’t get enough air in to breathe,” Rosemary says. “But I was a determined kid who loved life, which kept me going.”

As an adult, she had a particularly difficult and suffocating attack. Her physician knew she needed to try something else. There was, in fact, a treatment option her physician knew of that hadn't been available when Rosemary was a child. It was a biologic medicine and it had been decades in the making.

On June 20, 2003, the FDA approved Xolair® (omalizumab) for the treatment of moderate-to-severe persistent allergic asthma in adults and adolescents 12 years of age and older whose symptoms were not controlled by inhaled corticosteroids Indication and Important Safety Information. It was the first biologic therapy approved by the FDA to target the underlying cause of allergic asthma symptoms in patients like Rosemary.


IMPORTANT SAFETY INFORMATION

What is the most important information I should know about Xolair?

Severe allergic reaction. A severe allergic reaction called anaphylaxis can happen when you receive XOLAIR. The reaction can occur after the first dose, or after many doses. It may also occur right after a XOLAIR injection or days later. Anaphylaxis is a life-threatening condition and can lead to death. Go to the nearest emergency room right away if you have any of these symptoms of an allergic reaction:

  • wheezing, shortness of breath, cough, chest tightness, or trouble breathing
  • low blood pressure, dizziness, fainting, rapid or weak heartbeat, anxiety, or feeling of “impending doom”
  • flushing, itching, hives, or feeling warm
  • swelling of the throat or tongue, throat tightness, hoarse voice, or trouble swallowing

Your healthcare provider will monitor you closely for symptoms of an allergic reaction while you are receiving XOLAIR and for a period of time after your injection. Your healthcare provider should talk to you about getting medical treatment if you have symptoms of an allergic reaction after leaving the healthcare provider’s office or treatment center.

Do not receive XOLAIR if you are allergic to omalizumab or any of the ingredients in XOLAIR.



The approval was an important milestone in a quest that had started in the 1980s. Researchers at Genentech and elsewhere had been working hard over the years to find some way to help people whose asthma appeared to be connected to their allergies. While the standard approach was to treat the effects of the allergic reaction, these researchers were thinking about how to treat the underlying cause, which they suspected was an antibody called Immunoglobulin E (IgE).

Today, it’s well known that when people with allergic asthma are exposed to certain allergens, the immune system causes a cascade of reactions. For every allergen that enters the body, the immune system produces specific IgE antibodies; together, they attach to receptors on inflammatory cells called mast cells, triggering the release of chemical mediators that cause inflammation and can lead to swelling and narrowing of the airways.

But in 1993, researchers were only just beginning to put the pieces together. A team at Genentech had developed a molecule called omalizumab, which successfully helped block the IgE antibodies. They were very excited about the potential of the first biologic for allergic asthma, but were unsure what other roles IgE might play in the body, or what the effects of blocking that antibody would be.

“There was a lot of uncertainty,” says Dr. Karin Rosén, group medical director of the respiratory/immunology franchise in U.S. medical affairs at Genentech. “Yet Genentech embarked on this very complex journey in a disease area where many of the treating physicians weren’t even convinced that IgE actually played a role. It was brave, and the research had the potential to change the way we treat allergic asthma.”

The first years of studying omalizumab were disappointing. In 1994, Genentech set up a number of Phase II clinical trials for the medicine, hoping to validate the theory that excess IgE in the bloodstream was the trigger for a wide range of serious allergic reactions. But of the 240 patients who received the medicine in one of the key trials, only 11 improved.

“The results surprised everyone—the theory was sound,” says Dr. Thomas Casale, a professor of internal medicine at the University of South Florida who helped design the studies while at the University of Iowa. But instead of dropping the theory, Genentech and their research partners kept trying. Casale says it took time for them to understand what had gone wrong in the first trials. While they’d followed the dosing standards similar to those used in other monoclonal antibody trials, which were based on the patient’s weight, they realized they needed to come up with new standards, and base the dose on the patient’s established IgE levels.

Read more about Xolair® (omalizumab) and two doctors’ interesting observation.

So, in 1995, the team went back to the drawing board, starting a new clinical trial with different dosage levels. Taking a step back was just the ticket to moving the investigation forward. The trial showed positive results, proving the theory of anti-IgE in allergic asthma. Genentech then began collaborating with two other pharmaceutical companies, Novartis and Tanox, in 1996. They conducted several additional clinical trials with omalizumab, involving more than 4,000 people with allergic asthma worldwide. “When we saw the positive results, we were all excited,” says Dr. Casale. “These studies included unique designs, based on a primary endpoint of reducing asthma exacerbations; before, it was all symptoms or improvement in pulmonary functions.”

“They were truly innovative pioneers with these clinical trials,” says Andy Anderson, who joined Genentech in 2002 to help support Xolair as the company’s national respiratory liaison for respiratory practitioners and professional medical societies. Anderson had a personal stake in the development – he and the majority of his family suffer from moderate to severe allergic asthma and have experienced life-threatening asthma attacks. “The molecule was well before its time, but it shows that we were continually looking to address unmet needs, and it makes me filled with gratitude,” says Anderson.

After a few more hurdles – including additional submissions of patient safety and a revision to the application – Xolair was approved by the FDA, 10 years after the omalizumab molecule had been developed.

Today, researchers are continuing to explore the role of IgE in other conditions. “We’ve learned a lot about the biology of IgE,” says Dr. Casale. “This has provided many of us an opportunity to better understand the pathophysiology of a number of diseases.” Xolair is not approved to treat other allergic conditions.

“The success of Xolair took a very pioneering team thinking outside the box,” says Dr. Rosén, “and also the commitment and backing from the company.”


What it Treats

XOLAIR® (omalizumab) for subcutaneous use is an injectable prescription medicine used to treat:

  • moderate to severe persistent asthma in patients 6 years of age or older whose asthma symptoms are not controlled by asthma medicines called inhaled corticosteroids. A skin or blood test is performed to see if you have allergies to year-round allergens.
  • chronic idiopathic urticaria (CIU; chronic hives without a known cause) in patients 12 years of age and older who continue to have hives that are not controlled by H1 antihistamine treatment.

XOLAIR is not used to treat other allergic conditions, other forms of urticaria, acute bronchospasm or status asthmaticus.

Important Safety Information

What is the most important information I should know about XOLAIR?

Severe allergic reaction. A severe allergic reaction called anaphylaxis can happen when you receive XOLAIR. The reaction can occur after the first dose, or after many doses. It may also occur right after a XOLAIR injection or days later. Anaphylaxis is a life-threatening condition and can lead to death. Go to the nearest emergency room right away if you have any of these symptoms of an allergic reaction:

  • wheezing, shortness of breath, cough, chest tightness, or trouble breathing
  • low blood pressure, dizziness, fainting, rapid or weak heartbeat, anxiety, or feeling of “impending doom”
  • flushing, itching, hives, or feeling warm
  • swelling of the throat or tongue, throat tightness, hoarse voice, or trouble swallowing

Your healthcare provider will monitor you closely for symptoms of an allergic reaction while you are receiving XOLAIR and for a period of time after your injection. Your healthcare provider should talk to you about getting medical treatment if you have symptoms of an allergic reaction after leaving the healthcare provider’s office or treatment center.

Do not receive XOLAIR if you are allergic to omalizumab or any of the ingredients in XOLAIR.

Before receiving XOLAIR, tell your healthcare provider about all of your medical conditions, including if you:

  • have a latex allergy or any other allergies (such as food allergy or seasonal allergies). The needle cap on the XOLAIR prefilled syringe may contain latex.
  • have sudden breathing problems (bronchospasm)
  • have ever had a severe allergic reaction called anaphylaxis
  • have or have had a parasitic infection
  • have or have had cancer
  • are pregnant or plan to become pregnant. It is not known if XOLAIR may harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if XOLAIR passes into your breast milk. Talk with your healthcare provider about the best way to feed your baby while you receive XOLAIR.

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

How should I receive XOLAIR?

  • XOLAIR should be given by your healthcare provider, in a healthcare setting.
  • XOLAIR is given in 1 or more injections under the skin (subcutaneous), 1 time every 2 or 4 weeks.
  • In asthma patients, a blood test for a substance called IgE must be performed prior to starting XOLAIR to determine the appropriate dose and dosing frequency.
  • In patients with chronic hives, a blood test is not necessary to determine the dose or dosing frequency.
  • Do not decrease or stop taking any of your other asthma or hive medicine unless your healthcare providers tell you to.
  • You may not see improvement in your symptoms right away after XOLAIR

What are the possible side effects of XOLAIR?

XOLAIR may cause serious side effects, including:

  • See, “What is the most important information I should know about XOLAIR” regarding the risk of anaphylaxis.
  • Cancer. Cases of cancer were observed in some people who received XOLAIR.
  • Inflammation of your blood vessels. Rarely, this can happen in people with asthma who receive XOLAIR. This usually, but not always, happens in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered. It is not known whether this is caused by XOLAIR. Tell your healthcare provider right away if you have rash; chest pain; shortness of breath; or a feeling of pins and needles or numbness of your arms or legs.
  • Fever, muscle aches, and rash. Some people who take XOLAIR get these symptoms 1 to 5 days after receiving a XOLAIR injection. If you have any of these symptoms, tell your healthcare provider.
  • Parasitic infection. Some people who are at a high risk for parasite (worm) infections, get a parasite infection after receiving XOLAIR. Your healthcare provider can test your stool to check if you have a parasite infection.
  • Heart and circulation problems. Some people who receive XOLAIR have had chest pain, heart attack, blood clots in the lungs or legs, or temporary symptoms of weakness on one side of the body, slurred speech, or altered vision. It is not known whether this is caused by XOLAIR.

The most common side effects of XOLAIR:

  • In adults and children 12 years of age and older with asthma: pain especially in your arms and legs, dizziness, feeling tired, skin rash, bone fractures, and pain or discomfort of your ears.
  • In children 6 to less than 12 years of age with asthma: common cold symptoms, headache, fever, sore throat, pain or discomfort of your ear, abdominal pain, nausea, vomiting and nose bleeds.
  • In people with chronic idiopathic urticaria: nausea, headaches, swelling of the inside of your nose, throat or sinuses, cough, joint pain, and upper respiratory tract infection.

These are not all the possible side effects of XOLAIR. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555 or Novartis Pharmaceuticals Corporation at 888-669-6682.

Please see full Prescribing Information, including Medication Guide for additional Important Safety Information.