Approval Probability
TA Base Rate
Adjusted LOA
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Label indication DAWNZERA™ is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. DAWNZERA is a prekallikrein directed antisense oligonucleotide indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. ( 1 ) FDA label
Also known as ISIS 721744, IONIS-PKK-LRx
Donidalorsen · 5 trials · 2 indications
The time-adjusted HAE attack rate was calculated as number of IC HAE attacks occurring from Week 1 to Week 25, divided by the number of days the participant contributed to the period multiplied by 28 days. An HAE attack was defined as an event with signs or symptoms consistent with an attack in at least 1 of the locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the AE is considered related to the medicinal (investigational) product. TEAEs were defined as those AEs that either started or worsened in severity on or after the date/time of first administration of study drug in this OLE Study. TEAEs included both serious and non-serious TEAEs.
Clinical laboratory tests including clinical chemistry, hematology, coagulation, complement, inflammatory, urinalysis were performed. The percentage of participants with clinically meaningful changes were reported. Clinical meaningfulness was determined by the investigator.
Vital sign measurements including heart rate, respiratory rate, body temperature, systolic and diastolic blood pressure and pulse pressure were assessed. Percentage of participants with clinically meaningful changes in the vital signs were reported. Clinically meaningfulness was determined by the investigator.
The ECG parameters included ventricular rate, PR interval, QRS duration, QTc, QT corrected using the Fridericia's formula (QTcF), QT corrected using the Bazett's formula (QTcB), and overall interpretation. Percentage of participants with clinically meaningful changes in the ECG parameters were reported. Clinical meaningfulness was determined by the investigator.
Concomitant medications include medications that participants were exposed to on or after the first dose of ISIS 721744 in the OLE study. Percentage of participants who received at least one concomitant medication were reported.
The Week 1 to end of on-treatment period HAE attack rate was calculated for each participant as number of HAE attacks occurring from Week 1 to 28 days after the last dose date divided by the number of days the participant contributed to the period multiplied by 28 days. An HAE attack was defined as an event with signs or symptoms consistent with an attack in at least 1 of the locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
| Arm | Type | Description |
|---|---|---|
| Donidalorsen: Group 1 | EXPERIMENTAL | Participant weighing 9 kilograms (kg) to less than (\<)26 kg, will be administered donidalorsen over the period of one year. |
| Donidalorsen: Group 2 | EXPERIMENTAL | Participant weighing greater than or equal to (≥)26 kg to \<41 kg, will be administered donidalorsen over the period of one year. |
| Donidalorsen: Group 3 | EXPERIMENTAL | Participant weighing ≥41kg, will receive donidalorsen over the period of one year. |
| OLE Participants | EXPERIMENTAL | Group 1 and Group 2 participants will be administered donidalorsen by SC injection for up to 157 weeks. |
| Pooled Placebo | PLACEBO_COMPARATOR | Participants with hereditary angioedema type I/type II (HAE-1/HAE-2) received placebo subcutaneously (SC) either every 4 weeks (Weeks 1, 5, 9, 13, 17, and 21) or 8 weeks (Weeks 1, 9, and 17) |
| Cohort A: Donidalorsen 80 mg | EXPERIMENTAL | Participants with HAE-1/HAE-2 received donidalorsen, 80 mg, SC, every 4 weeks at Weeks 1, 5, 9, 13, 17, and 21. |
| Cohort B: Donidalorsen 80 mg | EXPERIMENTAL | Participants with HAE-1/HAE-2 received donidalorsen, 80 mg, SC, every 8 weeks at Weeks 1, 9, and 17. |
| HAE-1/HAE-2 | EXPERIMENTAL | Participants with hereditary angioedema Type I/Type II (HAE-1/HAE-2) who received placebo or donidalorsen, 80 milligrams (mg), SC once every 4 weeks, in the previous study ISIS 721744-CS2 (NCT04030598), received donidalorsen, 80 mg, SC once every 4 weeks, from Week 1 to Week 13 (Fixed Dosing Period). Starting From Week 17 (Flexible Dosing Period), participants had 3 different dosing options as: 80 mg every 4 weeks, 80 mg every 8 weeks for participants who were attack-free for ≥12 weeks, 100 mg every 4 weeks for participants who were not attack-free for ≥12 weeks up to Week 53 based on the investigator and sponsor medical monitor recommendation. Participants continued flexible dosing from Week 53 for up to approximately 209 weeks. |
| HAE-nC1-INH | EXPERIMENTAL | Participants with hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) who received donidalorsen, 80 mg, SC, once every 4 weeks, in the previous study ISIS 721744-CS2 (NCT04030598), continued to receive donidalorsen, 80 mg, SC once every 4 weeks, from Week 1 to Week 13 (Fixed Dosing Period). Starting From Week 17 (Flexible Dosing Period), participants had 2 different dosing options as: 80 mg every 4 weeks, and 100 mg every 4 weeks for participants who were not attack-free for ≥12 weeks up to Week 53 based on the investigator and sponsor medical monitor recommendation. Participants continued flexible dosing from Week 53 for up to approximately 209 weeks. |
| Part A: Placebo | PLACEBO_COMPARATOR | Participants with hereditary angioedema type I/type II (HAE-1/HAE-2) received placebo subcutaneously (SC) every 4 weeks at Weeks 1, 5, 9, and 13. |
| Part A: Donidalorsen 80 mg | EXPERIMENTAL | Participants with HAE-1/HAE-2 received donidalorsen, 80 mg, SC, every 4 weeks at Weeks 1, 5, 9, and 13. |
| Part B: Donidalorsen 80 mg | EXPERIMENTAL | Participants with hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) received donidalorsen, 80 mg, SC, every 4 weeks at Weeks 1, 5, 9, and 13. |
| Name | Type | Description |
|---|---|---|
| Donidalorsen | DRUG | Donidalorsen will be administered by subcutaneous (SC) injection. |
| Placebo | DRUG | Donidalorsen-matching placebo was administered by SC injection. |
Key Inclusion Criteria: 1. Must be between the ages of 2 and less than 12 years, inclusive, at the time of informed consent and, as applicable, assent. 2. Must weigh at least 9 kg at the time of informed consent and, as applicable, assent. 3. Documented diagnosis of HAE-1/HAE-2 based upon both of t...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Intellia Therapeutics, Inc. | NTLA | 3 | PHASE3 | NTLA-2002 |
| BioCryst Pharmaceuticals, Inc. | BCRX | 2 | PHASE3 | Berotralstat |
| Ionis Pharmaceuticals, Inc. | IONS | 1 | PHASE3 | Donidalorsen |
| Pharvaris N.V. | PHVS | 1 | PHASE2 | Deucrictibant |
| BioMarin Pharmaceutical Inc. | BMRN | 1 | PHASE1 | BMN 331 |
| Astria Therapeutics, Inc. | ATXS | 1 | PHASE2 | STAR-0215 |
Donidalorsen is an investigational RNA therapy being developed for the prophylactic treatment of hereditary angioedema (HAE), a rare immunological condition characterized by recurrent swelling attacks. It is designed as a preventive therapy rather than an on-demand treatment for acute attacks.
Donidalorsen targets KLKB1, the gene encoding plasma prekallikrein. It is an antisense oligonucleotide (ASO) that reduces production of prekallikrein, a precursor to plasma kallikrein, which is involved in the contact activation pathway that drives bradykinin generation and angioedema attacks in HAE.
Donidalorsen is being developed by Ionis Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker IONS. Ionis is the sponsor of the clinical development program evaluating the drug in hereditary angioedema.
Donidalorsen is in Phase 3 clinical development for hereditary angioedema. It is an investigational therapy and has not been approved by the FDA. The program includes completed Phase 2 and Phase 3 studies as well as ongoing Phase 3 trials.
Donidalorsen has been studied in five clinical trials. Key studies include OASIS-HAE (NCT05139810), a completed Phase 3 trial, a Phase 3 long-term safety and efficacy study (NCT05392114), a Phase 3 trial in children with HAE (NCT07298447), and a completed Phase 2 extension study (NCT04307381).
Yes. Donidalorsen has also been known as ISIS 721744 and IONIS-PKK-LRx. These names refer to the same antisense oligonucleotide candidate targeting KLKB1 that Ionis Pharmaceuticals is developing for hereditary angioedema, so searches under any of these names refer to the same drug.