Kalbitor (ecallantide) is a medicine used to treat sudden attacks of hereditary angioedema (HAE). During an HAE attack, swelling happens in different areas of the body, such as your face, hands, feet, gut, or throat. If it affects the gut, it can cause severe stomach pain. If swelling affects your throat, it can be deadly because it can close off your airway. Certain situations or triggers can cause these attacks to happen. Common triggers for attacks include stress, surgery, medical or dental procedures, infections, and tiredness.
HAE is a rare genetic condition that is caused by a problem with a gene that makes a blood protein called C1 inhibitor. In most cases of HAE, you do not have enough of this protein. In others, you have normal levels, but it does not work right. When this protein is missing or not working properly, the body releases too much of a substance called bradykinin. Bradykinin causes blood vessels to widen, which causes swelling that can be painful and life-threatening.
HAE medicines work in different ways to stop or prevent your attacks by lowering or preventing too much bradykinin from being made. Treatment depends on the type of HAE you have and how severe it is. It focuses on avoiding and managing attacks with medicine. Because attacks can happen at any time and are hard to predict, you need to take medicine regularly to prevent attacks. You also need rescue medicine (on-demand treatment) readily available to treat breakthrough attacks. Kalbitor is a medicine injected under the skin by a health care provider that is approved to treat sudden HAE attacks in adults and children aged 12 years or older.
How Does Kalbitor Work for Hereditary Angioedema?
Medicines called bradykinin inhibitors are used to treat and prevent HAE attacks. The main ingredient in Kalbitor is ecallantide, a medicine that blocks a protein called kallikrein. Kallikrein plays a key role in swelling because it causes the release of bradykinin. By blocking kallikrein, Kalbitor lowers the amount of bradykinin that your body makes, limits fluid buildup in the body, and eases pain and swelling from the HAE attack.
How Is Kalbitor Given?
Kalbitor is a liquid injected under the skin (subcutaneous) by a health care provider in a health care setting. For each dose, you will get three shots into your thigh, stomach area, or upper arm. You may receive another dose of three shots within 24 hours if you are still having symptoms or if they come back.
How Was Kalbitor Studied for Hereditary Angioedema?
Two clinical studies, known as EDEMA4 and EDEMA3, looked at whether Kalbitor was safe and effective for treating HAE attacks in people who were aged 10 years or older. Kalbitor was compared to a placebo that contained no medicine. People in the study did not know if they were getting Kalbitor or a placebo.
In both studies, people could take part if they had a confirmed diagnosis of HAE and arrived at the study site within eight hours after a moderate or severe attack began. Participants were given either a dose of Kalbitor 30 mg or a placebo injected under the skin. After receiving the study treatment, people stayed at the study site for at least four hours to have their symptoms monitored.
In either study, if a participant developed severe swelling of the upper airway within the first four hours, they could receive a dose of Kalbitor 30 mg. (If this happened, everyone knew it was the medicine being given and not a placebo.) In the EDEMA4 study, a second dose of Kalbitor 30 mg was allowed if symptoms did not improve, did not fully go away, or came back about 4-24 hours after the first dose.
The effects of Kalbitor were measured using the Mean Symptom Complex Severity (MSCS) score and the Treatment Outcome Score (TOS). The MSCS score measures symptoms at one point in time and is used to evaluate the severity of the HAE attack. People rated their symptoms using a scale of 0 = normal, 1 = mild, 2 = moderate, and 3 = severe. The score was recorded before treatment (baseline) and four hours after treatment. The TOS measures the response of each symptom to treatment. A TOS greater than 0 is considered an improvement in symptoms compared to baseline (0 = same, 50 = improvement, 100 = significant improvement).
The main goals of the studies were to measure the change in severity of symptoms after four hours and to see how well people responded to treatment at four hours.
Who Was Included in the Studies of Kalbitor?
There were 96 people in EDEMA4 and 72 people in EDEMA3, but some people were in both studies. There were a total of 143 unique people in the studies. Characteristics of the people in the studies are described below:
- The average age was about 36 years (range, 11-77).
- More than half of the people were female (66%), and the rest were male.
- Most people in both studies were White (about 86%). In EDEMA4, 6% were Black, 2% were Asian, and 3% identified as Hispanic.
- The average age at onset of HAE was 13 years of age in EDEMA4.
- HAE attacks occurred most often in the stomach (45%), or other areas such as head, neck, skin, genital areas, hands, or feet (38%), and throat (17%).
What Benefits Were Seen With Kalbitor in Studies?
In both studies, people who were given Kalbitor had a greater decrease in the severity of their attack at four hours compared to a placebo. They had a greater response to attack symptoms than people who were given a placebo at four hours. The table below shows the average of everyone’s results.
EDEMA4 | EDEMA3 | |||
|---|---|---|---|---|
| Kalbitor (n=48) | Placebo (n=48) | Kalbitor (n=36) | Placebo (n=36) | |
| Average Change in MSCS Score at 4 hours | -0.8 | -0.4 | -1.1 | -0.6 |
| Average change in TOS at 4 hours | 53 | 8 | 63 | 36 |
In both studies, more people in the placebo group needed additional medical care to treat symptoms that did not go away within 24 hours compared to those treated with Kalbitor. In the EDEMA4 study, some people had improvement in symptoms after a second dose of Kalbitor within 24 hours after the initial dose.
Your results may differ from those seen in clinical studies.
How Long Does It Take for Kalbitor to Work?
In the studies, Kalbitor improved symptoms of the HAE attack within four hours after it was given. For many people, symptoms improved within two hours after the dose was given and lasted for 24 hours.
How Can I Prevent and Manage Side Effects of Kalbitor?
It is important to tell your health care provider about any side effects you have during or after receiving Kalbitor. Some common side effects of Kalbitor are:
- Headache
- Nausea
- Diarrhea
- Fever
- Stuffy nose
- Redness, rash, swelling, itching, or bruising in the areas where Kalbitor is injected
If you have a headache or fever, using an over-the-counter (OTC) pain reliever or fever reducer may help. Talk with your health care provider about which OTC product may be best for you.
To help limit nausea, you can try simple methods such as eating bland foods, such as toast or crackers. Your health care provider may prescribe medicine to help manage nausea and vomiting.
If you have diarrhea, your health care provider may recommend that you take antidiarrhea medicine and drink more fluids to avoid dehydration.
If you have injection site pain, redness, or irritation after receiving Kalbitor, applying a cool compress to the area may help. Ask your health care provider if an over-the-counter (OTC) pain medicine or antihistamine may help.
Serious allergic reactions can happen, usually within one hour after receiving Kalbitor. This is why you need to receive Kalbitor from a health care provider in a health care setting. Symptoms may be similar to those of HAE. Tell your health care provider right away if you have symptoms of an allergic reaction during or after treatment with Kalbitor. These include:
- Shortness of breath, cough, chest tightness, trouble breathing
- Feeling dizzy, fainting, fast or weak heartbeat, feeling nervous
- Redness of the face, itching, hives, or feeling warm
- Throat or tongue swelling, throat tightness, hoarse voice, trouble swallowing
- Runny nose, stuffy nose, or sneezing
If your side effects get worse or do not go away, talk with your health care provider.
Is There Any Cost Assistance Available for Kalbitor?
There is a patient support program offered by the drugmaker that may help you afford Kalbitor. Your health care provider can help you get started. You can find out more at KALBITOR - Takeda Treatment Patient Support or by calling 866-888-0660.
