FAQs

Cold Agglutinin Disease (CAD) is a form of autoimmune hemolytic anemia (AIHA), which means the immune system mistakenly attacks and destroys red blood cells.

No, it’s important to know that Cold Agglutinin Disease is not cancer. Cold Agglutinin Disease is a form of autoimmune hemolytic anemia (AIHA), meaning the immune system mistakenly attacks and destroys red blood cells.

Symptoms of Cold Agglutinin Disease can be related to the immune system breaking down red blood cells (complement-mediated hemolysis) or cold-induced circulatory symptoms. Complement-mediated hemolysis may cause profound fatigue, anemia (not having enough red blood cells to carry oxygen through your body), shortness of breath, yellowing of the skin or eyes (also known as jaundice), and dark urine. The Cold Agglutinin Disease symptoms triggered by cold can include bluish or reddish discoloration of the skin (also known as acrocyanosis) and decreased blood flow to the fingers and toes (known as Raynaud’s phenomenon). In rare cases, it can cause a net-like pattern of reddish-blue skin discoloration called livedo reticularis, and skin ulcers or skin death in rare severe cases. Some people may experience pain or discomfort when they swallow cold food or drinks.

Cold Agglutinin Disease is a specific type of autoimmune hemolytic anemia, a category of diseases in which the immune system mistakenly attacks and destroys healthy red blood cells. In CAD, a type of antibodies known as cold agglutinins target red blood cells, the cells responsible for delivering oxygen through the bloodstream.

In some instances known as secondary Cold Agglutinin Disease, or Cold Agglutinin Syndrome, however, Cold Agglutinin Disease results from an underlying condition, including infectious diseases such as mumps, immune system disorders such as non-Hodgkin lymphoma, or connective tissue disorders such as rheumatoid arthritis.

A common misconception about Cold Agglutinin Disease is that it can be managed with cold avoidance alone. While cold can trigger symptoms, red blood cell destruction can still occur without cold exposure. In Cold Agglutinin Disease, the immune system makes antibodies (cold agglutinins) that activate the complement system, leading to the destruction of red blood cells (hemolysis).

Hemolysis is the process where red blood cells are broken down and destroyed.

Cold agglutinin antibodies mistakenly attach to red blood cells, causing them to clump together. This triggers the classical complement pathway, which attaches C1 proteins to these clumps, causing them to be destroyed via hemolysis.

Since hemolysis may be chronic in patients with Cold Agglutinin Disease, this can lead to fewer red blood cells, meaning less oxygen is delivered throughout your body. That can make you feel tired or short of breath. Ongoing hemolysis can also increase the risk of complications like fast or irregular heartbeat, yellowing of the skin or eyes (jaundice), or dark urine. It’s important to pay close attention to how you are feeling and be in regular contact with your doctor.

The immune system produces proteins called antibodies, which in normal circumstances help defend the body against invasive elements such as infectious bacteria. However, some antibodies, including agglutinins, mistakenly target the body’s healthy red blood cells.

In Cold Agglutinin Disease, cold agglutinins bind to red blood cells, particularly at cold temperatures, causing the red blood cells to clump together in a process known as agglutination. The red blood cells are then prematurely destroyed, leading to anemia and other symptoms.

Bilirubin is a pigment that is released when hemoglobin is broken down. When more bilirubin is released than the liver can process, the skin and eyes may acquire a yellow-orange tint, also known as jaundice.

Your blood needs to stay warm after you have your labs drawn because your blood can “agglutinate,” or clump together, below 37 °F, at which point the sample needs to be discarded. This agglutination is caused by the cold agglutinins attaching to the red blood cells, resulting in clumping.

In people with Cold Agglutinin Disease, your body mistakenly attacks the red blood cells and destroys them in a process known as hemolysis. The ongoing hemolysis happening in the body could lead to complications like anemia. 

Anemia occurs when you do not have enough red blood cells or when your red blood cells do not function properly. When you have Cold Agglutinin Disease and red blood cells are destroyed prematurely, they are unable to do their job of carrying oxygen throughout the body. If your organs and tissues do not get enough oxygen, they can’t function normally—which could make you feel tired.

In Cold Agglutinin Disease, cold agglutinins activate a part of the immune system known as the classical complement pathway. The pathway starts with a protein called C1 that binds to the red blood cell that is attached to cold agglutinin, leading to a complex chain of events that marks the red blood cell for destruction.

The first and only treatment approved to help reduce hemolysis in Cold Agglutinin Disease. ENJAYMO is a prescription medicine for the treatment of hemolysis due to Cold Agglutinin Disease in adults.

No. ENJAYMO is a chemotherapy-free treatment option that helps reduce hemolysis.

The efficacy and safety of ENJAYMO have been studied in two Phase 3 clinical trials.

In one study, participants with Cold Agglutinin Disease with no history of blood transfusion during the 6 months prior to starting the study were randomized to receive either ENJAYMO (n=22) or placebo* (n=20). The study was double blind, meaning that neither the participants nor the researchers knew whether they were receiving ENJAYMO or placebo.

ENJAYMO has also been studied in 24 participants with Cold Agglutinin Disease with at least 1 blood transfusion during the 6 months prior to starting treatment. The study was single arm and open label, meaning that all of the participants received ENJAYMO and they knew what drug they were given.

In both studies, responders:

• Improved hemoglobin^†
• Remained transfusion free^‡
• Did not need other medications for CAD

The effect of ENJAYMO on other factors was studied, including:

• Hemoglobin levels over time
• Bilirubin levels over time
• Impact of fatigue
• Symptoms of anemia

Discover the full study results.

Placebo=a harmless medicine with no therapeutic effect, used as a control in testing new drugs.

At least 1.5 g/dL increase in hemoglobin from the start of treatment in the double-blind, randomized, placebo-controlled trial, and a return to at least 12 g/dL or at least a 2 g/dL improvement from the start of treatment in the single-arm, open-label trial.

No blood transfusion from Week 5 through Week 26.

The impact of ENJAYMO treatment on fatigue in Cold Agglutinin Disease was investigated in a placebo-controlled study.

People taking ENJAYMO or placebo answered a questionnaire about their fatigue and its impact on their daily life. The survey was administered at each visit.

At 6 months, only people on ENJAYMO reported a meaningful improvement in their fatigue (not people on placebo). Discover the full study results.

FACIT-Fatigue measures the impact of fatigue on a scale of 0 (not at all) to 4 (very much so) for a total of 52 points. This 13-item survey (FACIT) included questions about:

• How fatigued they felt
• How weak and tired they felt
• Ability to do usual activities
• Need to take a nap to get through the day
• Frustration because of tiredness

ENJAYMO was studied in 2 clinical trials, CADENZA and CARDINAL, in patients with and without a history of blood transfusion. People living with Cold Agglutinin Disease may be considered for treatment with ENJAYMO whether or not they have received blood transfusions in their past. Discuss with your doctor what the best treatment approach is for you.

In the ENJAYMO clinical trial, some patients started to see improvement in hemoglobin levels at Week 3. Discover the full study results.

Individual treatment results will vary.

Serious infections (bacterial and viral) were reported in 15% (10/66) of patients receiving ENJAYMO from the two Phase 3 trials. These infections included:

• urinary tract infection with sepsis
• respiratory tract infection
• pneumonia
• otomastoiditis 
• skin infections

One patient (1.5%) died due to klebsiella pneumonia.

The most common side effects reported in patients on ENJAYMO were:

• increase in blood pressure
• urinary tract infection
• respiratory tract infection
• bacterial infection
• swelling in lower legs or hands
• joint pain
• headache
• nausea
• runny nose
• bluish color to the lips and skin
• dizziness
• feeling tired or weak
• cough
• changes in color or sensation in the fingers and toes (Raynaud’s phenomenon)

These are not all the possible side effects of ENJAYMO. See more safety information.

You should tell your doctor about any side effect that bothers you or does not go away. There are other possible side effects of ENJAYMO. For more information, ask your doctor or pharmacist.

Because ENJAYMO interacts with a pathway in your immune system that can increase risk of serious infections, your doctor will take precautionary steps to help protect you while on treatment. Before starting treatment you will need to be vaccinated against certain bacteria that can cause potentially life-threatening infections in your blood, lungs, or in or around your brain. Then during treatment with ENJAYMO, you may need additional vaccinations. Vaccination may not prevent serious infection. You should seek immediate medical attention if signs or symptoms of serious infection occur.

ENJAYMO is first given every week for 2 weeks, then you’ll get an infusion every 2 weeks after that. An infusion can take 1 to 2 hours plus an additional 2 hours after your first infusion to monitor for infusion and allergic reactions. Then for all future infusions, you should be monitored for infusion reactions for 1 hour.

If you miss an ENJAYMO infusion, be sure to call your doctor right away. Schedule your next dose as soon as possible, then continue with an infusion every 2 weeks. If it’s been more than 17 days since your last dose, you will need a dose of ENJAYMO every week for 2 weeks before returning to an infusion every second week. In clinical studies, some patients who stopped treatment with ENJAYMO saw a return of symptoms of hemolysis to pretreatment levels.

The Recordati Rare Diseases Financial Assistance Programs are designed to provide support for eligible patients who wouldn’t otherwise be able to access ENJAYMO. There are 2 options available: the Co-Pay Assistance Program (designed to help with treatment costs) and the Patient Assistance Program (designed to provide financial support to eligible patients with limited access to treatment due to insurance issues).*

The Recordati Rare Diseases Co-Pay Program (the “Program”) is not valid for prescriptions covered by or submitted for reimbursement under Medicare, Medicaid, VA, DoD, TRICARE®, or similar federal or state programs, including any state pharmaceutical assistance programs. The Program is not valid where prohibited by law, and savings may vary depending on patients’ out-of-pocket costs. Recordati Rare Diseases reserves the right to modify or terminate the Program at any time without notice. Patients will receive all Program details upon registration.