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Label indication GIVLAARI is indicated for the treatment of adults with acute hepatic porphyria (AHP). GIVLAARI is an aminolevulinate synthase 1-directed small interfering RNA indicated for the treatment of adults with acute hepatic porphyria (AHP). ( 1 ) FDA label
Also known as givosiran (ALN-AS1), ALN-AS1, GIVLAARI
givosiran · 4 trials · 9 indications
Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
Area under the concentration-time curve (AUC)
An AE is any untoward medical occurrence in a participant or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
| Arm | Type | Description |
|---|---|---|
| Givosiran/Givosiran | EXPERIMENTAL | Givosiran 2.5 mg/kg administered subcutaneously (SC), monthly (QM), for 6 months during the 6-Month Double-blind (DB) Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the Open-label Extension (OLE) Period. |
| Placebo/Givosiran | PLACEBO_COMPARATOR | Matching placebo (normal saline \[0.9% NaCl\]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period. |
| Givosiran with 5-probe cocktail | EXPERIMENTAL | - |
| Givosiran | EXPERIMENTAL | At the beginning of this study, participants received either givosiran 2.5 mg/kg subcutaneous (SC) injection once monthly(QM), givosiran 5.0 mg/kg SC injection QM, or givosiran 5.0 mg/kg SC injection once every 3 months (Q3M). Within a year, all participants were transitioned to givosiran 2.5 mg/kg SC injection QM. |
| givosiran (ALN-AS1) | ACTIVE_COMPARATOR | - |
| Sterile Normal Saline (0.9% NaCl) | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Givosiran | DRUG | Givosiran by SC |
| Placebo | DRUG | Matching placebo (normal saline \[0.9% NaCl\]) by SC |
| 5-probe cocktail | DRUG | includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan |
| givosiran (ALN-AS1) | DRUG | Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection |
| Sterile Normal Saline (0.9% NaCl) | DRUG | calculated volume to match active comparator |
Inclusion Criteria: * ≥ 12 years of age * Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, aminolevulinic acid (ALA) dehydratase deficient porphyria) * Elevated urinary or plasma porphobilinogen (PBG) or ALA values within the past...
Givosiran is used for the treatment of acute hepatic porphyria, including acute intermittent porphyria. It is an RNA therapy developed for this rare disease. The clinical program studied patients with acute hepatic porphyria and acute intermittent porphyria, including hereditary coproporphyria, variegate porphyria, and ALA dehydratase deficient porphyria.
Givosiran targets ALAS1, an enzyme involved in heme biosynthesis. It is an RNAi inhibitor that reduces ALAS1 levels. By targeting ALAS1, givosiran aims to lower the accumulation of toxic heme intermediates that cause porphyria attacks.
Givosiran is being developed by Alnylam Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker ALNY. Alnylam is the sponsor of the clinical trials evaluating givosiran in acute hepatic porphyria and acute intermittent porphyria.
Givosiran is in Phase 3 clinical development. The Phase 3 ENVISION study (NCT03338816) has been completed. The development program also includes completed Phase 1 trials. Givosiran is an investigational RNA therapy and has not been approved by the FDA.
Givosiran has been studied in completed clinical trials including the Phase 3 ENVISION trial (NCT03338816) in acute hepatic porphyrias, a Phase 1 drug interaction study (NCT03505853), a Phase 1 long-term safety study (NCT02949830), and a Phase 1 study in acute intermittent porphyria (NCT02452372). All four trials are completed.
Yes, givosiran is also known as ALN-AS1. ALN-AS1 was the earlier designation used for givosiran in clinical trial titles and development communications. Both names refer to the same investigational RNA therapy targeting ALAS1 for acute hepatic porphyria.