Donidalorsen: A Breakthrough RNA-Targeted Therapy for Hereditary Angioedema Moves closer to EU Approval
Rome,9 Jan.– Teh European Medicines Agency (EMA) has taken a significant step toward approving donidalorsen, an experimental RNA-targeted drug developed by Otsuka Pharmaceutical Netherlands BV for the routine prophylactic treatment of hereditary angioedema (HAE). This rare, perhaps life-threatening genetic disorder causes recurrent episodes of severe swelling in various parts of the body, including the hands, feet, genitals, stomach, face, and throat.
the marketing authorization request (MA) submission is based on promising results from the OASIS-HAE and OASISplus Phase 3 clinical trials, which evaluated the drug’s efficacy and safety. These studies included patients treated with donidalorsen administered every 4 weeks (Q4W) or every 8 weeks (Q8W), and also a cohort of patients who switched to donidalorsen from other therapies.
A novel Approach to HAE Treatment
Table of Contents
Donidalorsen is designed to precisely target and reduce the production of prekallikrein (PKK),a key protein in the pathway that triggers HAE attacks. If approved, it will be the first RNA-targeted therapy for HAE, offering a groundbreaking therapeutic option for patients.
“We believe that donidalorsen has the potential to advance the landscape of long-term prophylactic treatments for people with HAE,” said Andy Hodge, CEO of Otsuka Pharmaceutical Europe Ltd. “The acceptance of our marketing authorization application in the European Union is a significant milestone, bringing us one step closer to helping meet the unmet needs of HAE patients in Europe.”
Clinical Trial Results: A Game-Changer for Patients
In the OASIS-HAE and OASISplus trials, donidalorsen demonstrated a significant and long-lasting reduction in the rate of HAE attacks. Key findings include:
- A >90% reduction in the average monthly attack rate in both the Q4W and Q8W dosage groups.
- A clinically significant improvement in quality of life, as measured by the Angioedema Quality of Life Questionnaire (AE-QoL), especially in the Q4W group.
- High levels of disease control, with 91% of patients in the Q4W group reporting well-controlled symptoms according to the Angioedema Control Test (AECT).
In the OASISplus switch study, patients who transitioned to donidalorsen from other prophylactic treatments experienced an additional 62% reduction in mean monthly HAE attack rates compared to baseline. Notably,84% of patients surveyed preferred donidalorsen over their previous therapy.
Data from the ongoing Phase 2 OLE trial further underscored the drug’s efficacy, showing an average 96% reduction in HAE attack rates for up to two years of treatment.
Safety and Tolerability
Donidalorsen was well-tolerated across all studies, with no serious adverse events related to the treatment reported. Most adverse events were mild or moderate, with injection site reactions being the most common.
A Commitment to Rare Diseases
“Otsuka’s commitment to fighting rare diseases is further strengthened today,” said Alessandro Lattuada, Managing Director of Otsuka Pharmaceutical Italy. “Thanks to the collaboration with Ionis, a company strongly committed to the research and development of new RNA-based therapeutic options, Otsuka has successfully submitted the request for marketing authorization to EMA for donidalorsen. This represents an important step for us which, we hope, will bring an improvement in the care and quality of life of patients and their families.”
Key Takeaways: Donidalorsen at a Glance
| Aspect | Details |
|————————–|—————————————————————————–|
| Target | RNA, specifically reducing prekallikrein (PKK) production |
| Dosage | Every 4 weeks (Q4W) or every 8 weeks (Q8W) |
| Efficacy | >90% reduction in HAE attack rates; 96% reduction in Phase 2 OLE trial |
| Quality of Life | Significant improvement in AE-QoL scores |
| Disease Control | 91% of Q4W patients reported well-controlled symptoms (AECT) |
| Safety | Well-tolerated; mild to moderate injection site reactions most common |
Looking Ahead
The EMA’s acceptance of the marketing authorization request marks a pivotal moment in the fight against HAE. If approved, donidalorsen could revolutionize the treatment landscape, offering patients a safer, more effective, and long-lasting prophylactic option.
For more information on the clinical trials and the science behind donidalorsen, explore the detailed findings from the OASIS-HAE and OASISplus studies here.
Stay tuned as we continue to follow this groundbreaking development in the treatment of hereditary angioedema.
Donidalorsen: A Breakthrough RNA-Targeted Therapy for Hereditary Angioedema Moves Closer to EU Approval
In a significant development for the treatment of hereditary angioedema (HAE),the European medicines Agency (EMA) has accepted the marketing authorization request for donidalorsen,an innovative RNA-targeted therapy developed by Otsuka Pharmaceutical. To delve deeper into this groundbreaking advancement, we sat down with Dr. Elena Rossi, a leading expert in rare genetic disorders and a key opinion leader in HAE research.
Introduction to Donidalorsen and Its Mechanism of Action
Senior Editor: Dr. Rossi, thank you for joining us today.could you start by explaining what makes donidalorsen such a unique approach to treating HAE?
Dr. Elena Rossi: Absolutely. Donidalorsen represents a novel approach because it targets RNA, specifically reducing the production of prekallikrein (PKK), a protein that plays a critical role in the biochemical pathway triggering HAE attacks. By precisely modulating this pathway, donidalorsen offers a more targeted and potentially long-lasting solution compared to traditional therapies.
Clinical Trial Results: Efficacy and Safety
Senior Editor: the clinical trial results for donidalorsen have been quite extraordinary. Can you highlight some of the key findings?
dr. Elena Rossi: Certainly. The OASIS-HAE and OASISplus trials demonstrated remarkable efficacy. Patients experienced a greater than 90% reduction in monthly HAE attack rates, with some groups showing a 96% reduction in the Phase 2 open-label extension trial. Additionally, the drug was well-tolerated, with mild to moderate injection site reactions being the most common side effect. Importantly, patients reported significant improvements in their quality of life, as measured by the Angioedema Quality of Life Questionnaire (AE-QoL).
Impact on Patients and Disease Management
Senior Editor: How do you see donidalorsen impacting the daily lives of HAE patients and their families?
Dr. Elena Rossi: This therapy has the potential to be transformative. HAE is a debilitating condition that can cause unpredictable and severe swelling episodes, often leading to hospitalizations and a significant emotional burden.With donidalorsen, patients could experience fewer attacks, better disease control, and an overall betterment in their quality of life. the fact that it can be administered every 4 or 8 weeks also reduces the treatment burden, making it more convenient for patients.
Looking Ahead: The Road to Approval and Beyond
Senior Editor: With the EMA’s acceptance of the marketing authorization request, what are the next steps, and what does this meen for the future of HAE treatment?
Dr. Elena Rossi: The EMA’s acceptance is a pivotal milestone. If approved, donidalorsen will be the first RNA-targeted therapy for HAE, setting a new standard in treatment. It also opens the door for further research into RNA-based therapies for other rare diseases. For patients, this means access to a safer, more effective, and long-lasting prophylactic option that could significantly reduce the frequency and severity of attacks.
Conclusion
Senior Editor: Dr. Rossi, thank you for sharing yoru insights. It’s clear that donidalorsen has the potential to make a profound difference in the lives of HAE patients. We’ll be closely following its journey toward approval and beyond.
Dr. Elena Rossi: Thank you.It’s an exciting time for HAE research,and I’m hopeful that donidalorsen will soon become a valuable tool in our fight against this challenging condition.
