Ruconest (recombinant C1 esterase inhibitor) for hereditary angioedema

Last updated Jan. 15, 2024, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

What is Ruconest for hereditary angioedema?

Ruconest (recombinant C1 esterase inhibitor) is an approved therapy indicated for the on-demand treatment of swelling attacks in adults and adolescents with hereditary angioedema (HAE).

Administered via an intravenous or into-the-vein injection, Ruconest was developed and is marketed by Pharming.

Therapy snapshot

How does Ruconest work?

In the most common types of HAE, the lack of a protein called C1-esterase inhibitor (C1-INH) leads to the overproduction of bradykinin, a molecule that promotes fluid leakage and blood vessel widening. Bradykinin is known to drive swelling attacks in HAE.

Ruconest aims to provide patients with the C1-INH protein they are missing to help reduce bradykinin levels and control swelling.

Its main ingredient, conestat alfa, is a recombinant version of human C1-INH that’s produced in genetically engineered rabbits. The protein is then purified from their milk and mixed with other inactive ingredients to produce Ruconest.

Compared with other C1-INH products that are obtained from human blood donors — such as Berinert, Cinryze, or Haegarda — recombinant C1-INH is believed to pose a lower risk of transmission of infectious agents, and helps ensure therapy access, since it does not rely on the availability of donor blood.

Who can take Ruconest?

Ruconest was approved by the U.S. Food and Drug Administration (FDA) in July 2014 for the treatment of acute HAE attacks in adults and adolescents.

In the European Union, Ruconest was first approved for adults with HAE in October 2010. Its label later was expanded, first in February 2016 to include adolescents, and then again in April 2020 for children as young as age 2. The therapy also is approved in dozens of other countries globally for treating HAE attacks.

Who should not take Ruconest?

Ruconest is contraindicated, or not recommended, for individuals with a known or suspected allergy to rabbits or rabbit-derived products, or to people with a history of immediate and life-threatening allergic reactions, including a severe reaction called anaphylaxis, to C1-INH products.

While the therapy is approved for treating acute HAE attacks, its effectiveness for treating laryngeal attacks, or those that affect the throat and airways, has not been established.

How is Ruconest administered?

Ruconest is given as an intravenous injection at the onset of an acute HAE attack. Patients or their caregivers may be able to administer the injections after receiving appropriate training from a qualified healthcare professional.

The medication comes as a white-to-off-white powder in single-use vials that must be dissolved, or reconstituted, in sterile water before the injection. Each vial of medication contains 2,100 international units (IUs) of recombinant C1-INH, which should be reconstituted in 14 mL of sterile water. That yields a solution containing 150 IU of medication per mL of water.

The amount of Ruconest injected depends on the patient’s weight:

• Individuals weighing less than 84 kg (about 185 pounds) should receive a dose of 50 IU per kilogram of body weight.
  • The volume of the reconstituted solution that should be injected to achieve this dose can be calculated by dividing a person’s body weight in kilograms by three. For example, a person weighing 60 kg (about 132 pounds) would need a dose of 20 mL of Ruconest solution (60/3).
• Patients weighing 84 kg or more should be given a dose of 4,200 IU, or two vials, for a total volume of 28 mL.

The solution, which should be colorless, clear, and free of visible particles after mixing, should be administered immediately or stored in the refrigerator and used within eight hours; the medication should never be frozen. Ruconest should be slowly injected at room temperature over a period of about five minutes.

If attack symptoms persist after the first dose, a second injection at the same dose level can be given. Ruconest should never be given in amounts greater than 4,200 IU per dose, and no more than two doses should be given within a 24-hour period.

Prior to mixing, Ruconest should be stored at room temperature and protected from light.

Sterile water, syringes, antiseptic wipes, and a commercially available vial adapter and needle are required to administer Ruconest, but are not provided along with the medication.

Ruconest in clinical trials

Ruconest’s approvals were mainly backed by findings from a Phase 3 trial and its open-label extension phase, supported by two other randomized, controlled clinical trials.

That pivotal Phase 3 trial (NCT01188564) enrolled 75 HAE patients, ages 13 and older, who were randomly assigned to receive Ruconest (50 IU/kg) or a placebo at the time of an acute swelling attack. The median time to the onset of symptom relief with Ruconest was 90 minutes (1.5 hours), which was significantly shorter than the median time of 152 minutes (about 2.5 hours) for those on the placebo. Most participants on Ruconest achieved symptom relief with just one dose.

In the open-label extension, all trial participants were able to treat multiple attacks with Ruconest. The treatment was well tolerated with repeated use, with the onset of symptom relief occurring at a median of 75 minutes, or 1.25 hours. In the extension study, 97% of attacks required only a single dose of Ruconest.

These findings were generally consistent with two earlier clinical trials conducted in North America and Europe. The North American study, a Phase 2/3 trial (NCT00225147), enrolled HAE patients, ages 12 and older, who were randomly assigned to receive Ruconest (50 or 100 IU/kg) or a placebo to treat a single attack. In the European Phase 3 trial (NCT00262301),  HAE patients, ages 16 and older, were randomly assigned to receive Ruconest (100 IU/kg) or a placebo to treat an attack.

A pooled analysis concerning 70 patients showed that the time to the start of symptom relief was significantly shorter with either dose of Ruconest than with a placebo. The median time to the onset of symptom relief was about one hour at Ruconest’s highest dose and about two hours at the lower dose, compared with more than eight hours on the placebo. A single dose of Ruconest was sufficient to control the attack for most patients.

Both trials were followed by an open-label extension in which patients treated multiple attacks with Ruconest at a dose of 50 IU/kg. Findings from both extension phases demonstrated the continued efficacy of Ruconest. More than 90% of attacks were responsive to treatment within four hours in the North American study, similar to the 87% observed in the European study.

Other trials

An open-label Phase 2 trial (NCT01359969) involving pediatric HAE patients, ages 2-13, supported the expanded approval of Ruconest in the EU to include children as young as age 2. A total of 73 attacks across 20 children were treated with Ruconest at a dose of 50 IU/kg. The treatment was found to be safe, well tolerated, and effective in these young patients, with a median time to symptom relief of about one hour.

Another Phase 2 study (NCT02247739) was conducted to evaluate the use of Ruconest as a prophylactic treatment to prevent swelling attacks in HAE patients. This trial enrolled 32 HAE patients, ages 13 and older, who had been experiencing recurrent swelling attacks. All participants received twice weekly Ruconest (50 IU/kg), once weekly Ruconest, and a placebo, in random order, for four weeks or about one month each.

Results showed that the mean number of HAE attacks while on Ruconest was significantly lower than while on the placebo. The participants experienced a mean of 2.7 attacks with twice weekly treatment, 4.4 attacks with once weekly treatment, and 7.2 attacks while on the placebo. Prophylactic treatment with Ruconest also was found to be well tolerated.

Common side effects of Ruconest

The most common adverse reactions reported in clinical trials of Ruconest were:

• headache
• nausea
• diarrhea.

Allergic reactions

The most serious adverse event reported in Ruconest clinical trials was anaphylactic shock, a life-threatening allergic reaction in which a person’s airways may close. Other signs of allergic reactions also may occur, including hives, welts, chest tightness, wheezing, and low blood pressure.

Should symptoms of anaphylaxis or other severe allergic reactions occur, Ruconest should be stopped and appropriate treatment started. Allergic reactions may have symptoms similar to those of HAE attacks, so treatment methods should be carefully considered.

Blood clots

Serious thromboembolic events, or blood clots, have been reported with the use of human blood-derived C1-INH products when given at their recommended dose, especially in patients with known risk factors. Such risk factors may include the presence of an indwelling catheter — a urinary catheter left in place — for repeated injections, a history of thrombosis, or underlying atherosclerosis, which is the buildup of plaque in arteries. The use of oral contraceptives or other hormonal medications, morbid obesity, and immobility are other such risk factors.

Patients with known risk factors should be monitored for blood clots during and after Ruconest administration.

Use in pregnancy and breastfeeding

Well-controlled studies on the use of Ruconest in pregnant women are lacking, but limited existing data have not found any adverse effects to the mother or the developing fetus. Still, those data are insufficient to establish Ruconest’s safety in this population. Patients using Ruconest should discuss the matter of pregnancy with their doctors.

Ruconest’s effects on human breast milk or on the nursing infant are not known. The benefits of breastfeeding, along with the mother’s need for Ruconest, and any potential adverse effects to the breastfed child should all be considered when deciding if the therapy should be used during breastfeeding.

Angioedema News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.