Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ALN-AGT01
Zilebesiran · 5 trials · 4 indications
24-hour ABPM was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33, 2. the number of successful nighttime readings were ≥11, 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly mean was the average of BP by each hour of the day. The 24-hour mean was the average of the hourly means. Least squares (LS) mean and standard error (SE) were calculated using a mixed model repeated measures (MMRM) approach.
An AE is any untoward medical occurrence in a patient or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
| Arm | Type | Description |
|---|---|---|
| Zilebesiran 300 mg | EXPERIMENTAL | Participants will be administered 300 mg zilebesiran subcutaneously (SC) once every 6 months as add-on therapy to their standard of care antihypertensive medications. |
| Placebo | PLACEBO_COMPARATOR | Participants will be administered placebo SC once every 6 months as add-on therapy to their standard of care antihypertensive medications. |
| Zilebesiran | EXPERIMENTAL | Participants will receive zilebesiran on Day 1 of the 6-month double-blind (DB) treatment period. Participants must be on stable doses of at least 2, but not more than 4, antihypertensive medications for at least 30 days prior to screening and plan to remain on stable doses of these medications during screening and through the DB treatment period. |
| Zilebesiran 150 Milligrams (mg) Once Every 6 Months (Q6M) | EXPERIMENTAL | Participants receive zilebesiran, 150 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed. |
| Zilebesiran 300 mg Q6M | EXPERIMENTAL | Participants receive zilebesiran, 300 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed. |
| Zilebesiran 300 mg Q3M | EXPERIMENTAL | Participants receive zilebesiran, 300 mg, SC injection, Q3M, during the 12-month DB period. Participants continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Upon implementation of Amendment 6, the DB Extension period was closed. |
| Zilebesiran 600 mg Q6M | EXPERIMENTAL | Participants receive zilebesiran, 600 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed. |
| Part A: SAD: ALN-AGT01 | EXPERIMENTAL | Participants will be administered a single dose of ALN-AGT01. |
| Part A: SAD: ALN-AGT01-Matching Placebo | PLACEBO_COMPARATOR | Participants will be administered a single dose of ALN-AGT01-matching placebo. |
| Part B: SD: ALN-AGT01 | EXPERIMENTAL | Participants with controlled salt intake will be administered a single dose of ALN-AGT01. |
| Part B: SD: ALN-AGT01-Matching Placebo | PLACEBO_COMPARATOR | Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo. |
| Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo | EXPERIMENTAL | Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo. |
| Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan | ACTIVE_COMPARATOR | Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan. |
| Part E: Open Label: ALN-AGT01 + Irbesartan | EXPERIMENTAL | Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan. |
| Name | Type | Description |
|---|---|---|
| Zilebesiran | DRUG | Zilebesiran will be administered SC |
| Placebo | DRUG | Placebo will be administered SC |
| ALN-AGT01 | DRUG | ALN-AGT01 administered by SC injection |
| ALN-AGT01-Matching Placebo | DRUG | Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC. |
| Irbesartan | DRUG | Irbesartan will be administered orally. |
| Irbesartan-Matching Placebo | DRUG | Irbesartan-matching placebo will be administered orally. |
Inclusion Criteria: * Is 18 years or older for patients with established cardiovascular disease (CVD) * Is 55 years or older for patients with high risk for CVD * Has established CVD (defined as coronary, cerebrovascular, or peripheral artery disease) or high risk for CVD * Has treated hypertension...
Top 4 of 19 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| United Therapeutics Corporation | UTHR | 1 | PHASE3 | Ralinepag |
| Roivant Sciences Ltd. | ROIV | 3 | PHASE3 | Mosliciguat |
| Eli Lilly and Company | LLY | 1 | PHASE3 | Lepodisiran |
| Illumina, Inc. | ILMN | 1 | PHASE1 | 18F-mFBG for administration |
Zilebesiran is an investigational RNA therapy being developed for hypertension in patients at high cardiovascular risk or with established cardiovascular disease. It is also being studied in mild to moderate hypertension. It is designed to be given as an add-on to standard antihypertensive medications in patients whose blood pressure is not adequately controlled.
Zilebesiran is a small interfering RNA (siRNA) therapy. It targets and reduces the production of a protein involved in blood pressure regulation, leading to sustained blood pressure lowering. As an siRNA, it works by silencing the messenger RNA that encodes this protein, which may allow for less frequent dosing than daily oral antihypertensives.
Zilebesiran is being developed by Alnylam Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker ALNY. Alnylam is a biopharmaceutical company focused on RNA interference therapeutics.
Zilebesiran is in Phase 2 clinical development for hypertension, with a Phase 3 trial currently recruiting. The Phase 3 trial, NCT07181109, is evaluating zilebesiran in patients with hypertension not adequately controlled and with either established cardiovascular disease or high risk for cardiovascular disease.
Zilebesiran is being studied in three clinical trials. The Phase 3 trial NCT07181109 is recruiting 11,000 patients with hypertension and high cardiovascular risk. The Phase 2 KARDIA-3 trial (NCT06272487) completed with 375 patients. A Phase 1 trial in Japanese patients (NCT06423352) completed with 36 patients.
Zilebesiran is an investigational siRNA therapy and is not approved by the FDA. It is distinct from other antihypertensive medications and is being developed as a potential add-on treatment for patients with hypertension and high cardiovascular risk.