Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Donidalorsen · 6 trials · 3 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).
The safety and tolerability of multiple doses of Donidalorsen will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with Donidalorsen.
Maximum Donidalorsen plasma concentration, Cmax (ug/mL) will be assessed following SC administration
Time to peak Donidalorsen plasma concentration, Tmax (hours) will be assessed following SC administration
Effects of Donidalorsen on plasma PKK concentration after multiple doses of Donidalorsen compared to baseline
| 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. |
| Donidalorsen | EXPERIMENTAL | Ascending single and multiple doses of Donidalorsen administered subcutaneously |
| Placebo (sterile saline 0.9%) | PLACEBO_COMPARATOR | Calculated volume to match active comparator |
| 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, Normal Saline Administration |
| 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 | Dose 1 of BMN 331 |
| Astria Therapeutics, Inc. | ATXS | 1 | PHASE2 | STAR-0215 |
Donidalorsen is an investigational drug being studied for the prophylactic treatment of hereditary angioedema (HAE), a condition characterized by recurrent episodes of severe swelling. It is also being evaluated in healthy volunteers. Donidalorsen is not yet approved and is in clinical development.
Donidalorsen targets KLKB1, which encodes plasma prekallikrein. It is an antisense oligonucleotide (ASO) designed to reduce the production of prekallikrein, a protein involved in the pathway that leads to swelling attacks in hereditary angioedema.
Donidalorsen is being developed by Ionis Pharmaceuticals, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol IONS.
Donidalorsen is in clinical development. It has completed Phase 2 and Phase 3 trials and is currently being studied in a Phase 3 trial in children with hereditary angioedema. It is not FDA approved.
Donidalorsen has been studied in several trials, including NCT05139810 (OASIS-HAE), a completed Phase 3 study in participants with HAE, and NCT05392114, an active Phase 3 long-term safety study. A Phase 3 trial in children (NCT07298447) is currently recruiting.
Yes, Donidalorsen is also known as ISIS 721744 or IONIS-PKK-LRx, as referenced in clinical trial titles. These names refer to the same investigational drug.