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Donidalorsen

Donidalorsen is an innovative drug being studied in clinical trials for the treatment of Hereditary Angioedema (HAE). This article explores the ongoing research, potential benefits, and important information about Donidalorsen in various clinical trial phases. The drug, also known as ISIS 721744 or IONIS-PKK-LRx, is administered subcutaneously and shows promise in reducing HAE attacks and improving the quality of life for patients with this rare genetic condition.

Table of Contents

What is Donidalorsen?

Donidalorsen is a new medication being developed for the treatment of Hereditary Angioedema (HAE). It is also known by other names such as ISIS 721744 and IONIS-PKK-LRx[1]. This drug is currently undergoing clinical trials to evaluate its safety and effectiveness in treating HAE, a rare genetic condition that causes sudden and potentially life-threatening swelling in various parts of the body.

How Does Donidalorsen Work?

Donidalorsen works by targeting a specific protein in the body called prekallikrein (PKK). PKK plays a crucial role in the development of HAE attacks. By reducing the levels of PKK in the blood, donidalorsen aims to prevent or reduce the frequency and severity of HAE attacks[2]. This approach is different from some other HAE treatments that focus on replacing missing proteins or blocking the effects of substances that cause swelling.

What Condition Does Donidalorsen Treat?

Donidalorsen is specifically designed to treat Hereditary Angioedema (HAE). HAE is a rare genetic disorder that affects the immune system. People with HAE experience sudden episodes of swelling in various parts of the body, including:

  • Skin (face, hands, feet)
  • Gastrointestinal tract (causing severe abdominal pain)
  • Airways (which can be life-threatening)

These swelling attacks can be painful, disfiguring, and in some cases, dangerous if they affect the airways. Donidalorsen aims to prevent these attacks and improve the quality of life for people living with HAE[3].

Clinical Trials and Research

Donidalorsen is currently being studied in several clinical trials to assess its safety and effectiveness. These trials include:

  • Phase 2 studies to evaluate the clinical efficacy and safety in HAE patients[2]
  • Phase 3 studies to further assess long-term safety and efficacy[3]
  • Open-label extension studies to allow participants from earlier trials to continue receiving the medication[4]
  • Expanded Access Program to provide pre-approval access to eligible patients[1]

These studies involve patients with different types of HAE, including HAE type 1, type 2, and HAE with normal C1-inhibitor levels.

Administration and Dosage

Donidalorsen is administered through subcutaneous (SC) injections. This means the medication is injected just under the skin, typically in the abdomen, thigh, or upper arm. The dosing schedule being studied includes:

  • Monthly injections (every 4 weeks)[5]
  • Bi-monthly injections (every 8 weeks)[5]

The exact dosage and frequency may vary depending on the individual patient and the results of ongoing clinical trials.

Effectiveness of Donidalorsen

Early clinical trials have shown promising results for donidalorsen in treating HAE. The medication has demonstrated the ability to:

  • Reduce the frequency of HAE attacks[2]
  • Decrease the severity of attacks when they do occur[5]
  • Lower the need for on-demand medications to treat acute attacks[2]

Researchers are measuring the effectiveness of donidalorsen by looking at factors such as the number of HAE attacks per month, the percentage of patients who become attack-free, and the reduction in moderate or severe attacks[3].

Safety and Side Effects

As with any new medication, the safety of donidalorsen is being carefully evaluated in clinical trials. Researchers are monitoring for any adverse events (side effects) that may be related to the treatment[6]. While specific side effects are still being studied, common side effects of subcutaneous injections may include:

  • Injection site reactions (redness, swelling, or itching at the injection site)
  • Mild pain or discomfort during injection

It’s important to note that the full safety profile of donidalorsen will become clearer as more data from clinical trials becomes available.

Impact on Quality of Life

One of the key goals of donidalorsen treatment is to improve the quality of life for people living with HAE. Researchers are using specific tools to measure this impact, including:

  • Angioedema Quality of Life (AE-QoL) Questionnaire: This measures how HAE affects various aspects of a patient’s life, including functioning, fatigue/mood, fears/shame, and food-related issues[4].
  • Angioedema Control Test (AECT): This helps identify how well a patient’s HAE is controlled[5].

By reducing the frequency and severity of HAE attacks, donidalorsen aims to help patients lead more normal, less disrupted lives.

Future Prospects

Donidalorsen is still in the research and development phase, but it shows promise as a potential new treatment option for people with HAE. If approved, it could offer several advantages:

  • Less frequent dosing compared to some existing treatments
  • A new mechanism of action that may be effective for patients who don’t respond well to current therapies
  • Potential for long-term prevention of HAE attacks

As clinical trials progress, more information will become available about the effectiveness, safety, and potential role of donidalorsen in HAE treatment[3].

Aspect Details
Drug Name Donidalorsen (also known as ISIS 721744 or IONIS-PKK-LRx)
Condition Treated Hereditary Angioedema (HAE)
Administration Method Subcutaneous (SC) injection
Dosing Frequency Once monthly or every other month (varies by trial)
Primary Outcome Measures Reduction in HAE attack frequency, safety profile
Secondary Outcome Measures Quality of life improvements, reduction in attack severity, use of on-demand medication
Trial Phases Phase 1, Phase 2, and Phase 3 studies
Trial Durations Ranging from 25 weeks to over 1 year, with some extended treatment periods
Key Biomarkers Plasma Prekallikrein (PKK) levels, cleaved High Molecular Weight Kininogen (cHMWK) levels
Patient Population Adults with HAE-1, HAE-2, and in some trials, HAE with normal C1-inhibitor

FAQ

  • What is Donidalorsen and how does it work? Donidalorsen is a drug being studied for the treatment of Hereditary Angioedema (HAE). It works by inhibiting prekallikrein (PKK), a protein involved in the process that leads to HAE attacks. By reducing PKK levels, Donidalorsen aims to prevent or decrease the frequency and severity of HAE attacks.
  • How is Donidalorsen administered? Donidalorsen is administered through subcutaneous (SC) injections, which means it's injected just under the skin. Depending on the specific trial, it may be given once monthly or every other month in areas such as the abdomen, thigh, or upper arm.
  • What are the main goals of the Donidalorsen clinical trials? The main goals of the Donidalorsen clinical trials are to evaluate its safety, efficacy, and tolerability in patients with HAE. Researchers are particularly interested in how well it reduces the frequency of HAE attacks, improves quality of life, and how it compares to existing treatments or placebo.
  • What types of HAE are being studied in these trials? The clinical trials are studying Donidalorsen in patients with different types of HAE, including HAE type 1 (HAE-1), HAE type 2 (HAE-2), and in some cases, HAE with normal C1-inhibitor (HAE-nC1-INH).
  • How long do the clinical trials for Donidalorsen typically last? The duration of Donidalorsen clinical trials varies, but many last several months to over a year. For example, some trials have treatment periods of 25 weeks, while others extend up to 53 weeks or even longer in extended treatment periods. This allows researchers to assess both short-term and long-term effects of the drug.

Ongoing Clinical Trials on Donidalorsen

  • A study of donidalorsen for children with hereditary angioedema

    Recruiting

    3 1 1
    Investigated drugs:
    Italy Poland Spain

  • Study on the Safety of Donidalorsen for Patients with Hereditary Angioedema

    Not recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    The Netherlands

  • Study on Long-Term Safety of Donidalorsen for Patients with Hereditary Angioedema

    Not recruiting

    3 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Bulgaria France Germany Italy The Netherlands +2

Glossary

  • Hereditary Angioedema (HAE): A rare genetic disorder characterized by recurrent episodes of severe swelling in various parts of the body, including the limbs, face, intestinal tract, and airway.
  • Subcutaneous (SC) injection: A method of administering medication by injecting it into the layer of tissue just beneath the skin.
  • Prekallikrein (PKK): A protein in the blood that, when activated, plays a role in the process leading to HAE attacks.
  • C1-inhibitor (C1-INH): A protein that helps regulate various complex systems in the body. In most cases of HAE, this protein is either missing or not functioning properly.
  • Angioedema Quality of Life (AE-QoL) Questionnaire: A tool used to measure how HAE impacts a patient's quality of life, covering areas such as functioning, fatigue/mood, fears/shame, and food.
  • Placebo: An inactive substance used in clinical trials to compare the effects of a drug against no treatment.
  • Pharmacokinetics: The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion.
  • Pharmacodynamics: The study of how a drug affects the body, including its mechanism of action and biochemical effects.
  • Expanded Access Program (EAP): A program that allows patients with serious or life-threatening conditions to access investigational drugs outside of clinical trials.
  • Time-normalized HAE Attacks: A measure used in clinical trials to standardize the number of HAE attacks a patient experiences over a specific time period, typically expressed as attacks per month.

References

  1. https://clinicaltrials.gov/study/NCT06415448
  2. https://clinicaltrials.gov/study/NCT04030598
  3. https://clinicaltrials.gov/study/NCT05392114
  4. https://clinicaltrials.eu/trial/study-on-the-safety-of-donidalorsen-for-patients-with-hereditary-angioedema/
  5. https://clinicaltrials.gov/study/NCT05139810
  6. https://clinicaltrials.gov/study/NCT03263507