What to Know About Yartemlea for Transplant-Associated Thrombotic Microangiopathy

How Does Yartemlea Work for TA-TMA?

Yartemlea is a complement inhibitor. It works by blocking MASP-2. MASP-2 is an enzyme involved in the lectin pathway of the complement system, which is part of the body’s immune response. The complement system can be activated by three pathways: the classical pathway, alternative pathway, and lectin pathway.

In TA-TMA, injury to endothelial cells can directly activate the lectin pathway, which can cause damage and clot formation in small blood vessels. By blocking MASP-2, Yartemlea reduces lectin pathway activity. This is thought to help stop the damaging, clot-promoting effects in small blood vessels.

How Is Yartemlea Given?

Yartemlea is given as an intravenous (IV) infusion. A health care professional will prepare the medicine as a liquid solution in an IV bag or syringe. The medicine will flow through a small tube into your vein. It takes about 30 minutes.

Yartemlea is administered by a health care professional. It is typically given once a week. If your signs and symptoms of TA-TMA do not improve enough, your health care provider may increase it to twice a week. 

If you weigh 110 pounds (50 kg) or more, the recommended dosage is 370 mg once weekly. If you weigh less than 110 pounds, your health care provider will calculate your dose based on your body weight.

How Was Yartemlea Studied for TA-TMA?

Researchers tested how well Yartemlea worked in two groups of people with TA-TMA. The first group came from a clinical trial called the TA-TMA study and the second group was part of a special program.

The TA-TMA study included 28 people who developed TA-TMA after a stem cell transplant. The typical time from a stem cell transplant to a TA-TMA diagnosis was 74 days (median, or middle value), with some cases occurring as early as 21 days and others as late as 436 days after transplant. Everyone in the study had a confirmed diagnosis of TA-TMA based on certain blood test results and their kidneys not working as well as they should. Once their TA-TMA was diagnosed, people in this study typically started treatment with Yartemlea about two weeks later (median, 13.5 days) but ranged anywhere from four days to 196 days. The following information describes the 28 adults before study treatment began:

• Ages ranged from 22 to 68 years, with a median age of 48 years.
• 71% were male and 29% were female.
• 61% were White, 25% were Asian, 7% were Black or African American, 4% were Native Hawaiian or other Pacific Islander, and 4% were of other races.
• 7% were Hispanic or Latino, and 93% were not Hispanic or Latino.
• Most people had organ problems (96%), including kidney problems (75%).
• Most people had infections (86%).
• Moderate to severe GVHD was present in many people (68%).

The medicine was also studied in a second group of people with confirmed TA-TMA who received Yartemlea through an expanded access program (EAP). EAPs allow people to receive a medicine outside of a clinical trial if they have a serious, life-threatening condition and no other effective treatments are available.

More than 200 people were treated with Yartemlea through the EAP, but only 19 people had enough individual data available to assess how well the medicine worked. Of those 19 people, the typical time from a stem cell transplant to TA-TMA diagnosis in this group was 81 days (median) but ranged from 24 to 452 days. After TA-TMA was diagnosed, treatment with Yartemlea generally began more quickly in the EAP group, ranging from the same day to 52 days after diagnosis, with a median of three days. The following information describes this group of 19 people, made up of 13 adults and six children, before treatment began:

• Adults: Ages ranged from 19 to 71 years, with a median age of 62 years; 38% were male, and 62% were female.
• Children: Ages ranged from 5 to 15 years, with a median age of 10.5 years; 33% were boys, and 67% were girls.
• All participants had organ problems, including kidney problems in all adults and 83% of children.
• Infections were common, affecting all children and 62% of adults.
• Moderate to severe GVHD was present in 83% of children and 85% of adults.
• Race and ethnicity information was not reported.

People in both studies received Yartemlea once weekly. The main goal of both studies was to see how many people had a response to treatment. In other words, how many people got better. To count as a response, the following signs of TMA had to improve:

• Key blood test markers of TA-TMA, including improvements in platelet counts and LDH levels
• Overall health, shown by either improved organ health or no longer needing blood transfusions

What Are the Main Benefits of Yartemlea Based on Studies?

In both studies, the condition of many people improved while receiving treatment with Yartemlea for TA-TMA. The table below summarizes the main results:

Together, these results show that Yartemlea can be an effective treatment for improving blood markers of TA-TMA, including platelets and LDH. It may also improve organ health or help patients no longer need blood transfusions.

In addition to the main study goal, researchers also looked at many other outcomes to understand how people responded to treatment, such as survival, average changes in certain blood or urine tests, and the speed at which people improved after starting Yartemlea.

Survival: Out of the 28 participants in the TA-TMA study who received at least one dose of Yartemlea, 68% were alive 100 days after diagnosis of TA-TMA. Among those who responded to treatment, 94% were alive at 100 days. Median overall survival was 274 days.

Did Studies Compare Yartemlea With a Placebo?

In the clinical study and expanded access program, everyone received Yartemlea; there was no placebo group. (A placebo contains no medicine and can help compare how well a treatment works.)

To better understand if the medicine improves survival, researchers later compared people with high-risk TA-TMA who received Yartemlea with a group of similar people identified from a transplant registry who did not receive the medicine. People treated with Yartemlea were about four times less likely to die, suggesting the medicine may improve survival in high-risk TA-TMA cases.

Individual results may vary, and your health care provider can discuss what this may mean for you.

What Should I Know About the Side Effects of Yartemlea?

As with most medicines, side effects can happen while using Yartemlea. You and your health care provider will talk about the possible risks and benefits. Because TA-TMA is a serious and life-threatening condition, your health care provider may determine that the potential benefits of treatment are greater than the risks.

Many study participants had side effects while receiving Yartemlea. In the TA-TMA study, the most common side effects (affecting at least 20% of participants) were viral infections, sepsis, bleeding, diarrhea, vomiting, low levels of white blood cells called neutrophils (neutropenia), fever, tiredness, and low potassium levels.

More than half (61%) the participants reported serious side effects, with the most common ones being kidney problems, confusion, breathing problems, sepsis or septic shock, fluid buildup in the lungs, and vomiting. A small number of people that developed serious side effects passed away (7%).

That said, many of these problems were consistent with what is typically seen in people after a stem cell transplant or with TA-TMA, and the researchers did not identify any new or unexpected safety concerns. 

Is There Any Cost Assistance Available?

A patient support program may be available for Yartemlea. For more information, including possible financial assistance options, call 844-927-8361 or visit the drugmaker’s website.